Unnamed: 0
int64 0
14.2k
| ReviewID
int64 2.14M
32.7M
| Target
stringlengths 12
3.68k
| Background
stringlengths 46
5.35k
⌀ | Abstract
stringlengths 263
730k
⌀ |
|---|---|---|---|---|
11,100 | 27,926,497 | Consequently , compared with conventional strategy , CCTA seemed not to improve clinical outcomes for patients with low-to-intermediate risk chest pain | Coronary computed tomographic angiography ( CCTA ) can image the coronary vasculature rapidly and detect the presence and severity of luminal stenosis accurately .
However , whether CCTA based care strategy could gain more benefits than conventional strategy with functional tests for patients with low-to-intermediate risk chest pain remains unknown .
In this study we performed a meta- analysis to compare the clinical efficacy of CCTA versus conventional strategy . | BACKGROUND Many patients have symptoms suggestive of coronary artery disease ( CAD ) and are often evaluated with the use of diagnostic testing , although there are limited data from r and omized trials to guide care . METHODS We r and omly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography ( CTA ) or to functional testing ( exercise electrocardiography , nuclear stress testing , or stress echocardiography ) . The composite primary end point was death , myocardial infa rct ion , hospitalization for unstable angina , or major procedural complication . Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure . RESULTS The mean age of the patients was 60.8±8.3 years , 52.7 % were women , and 87.7 % had chest pain or dyspnea on exertion . The mean pretest likelihood of obstructive CAD was 53.3±21.4 % . Over a median follow-up period of 25 months , a primary end-point event occurred in 164 of 4996 patients in the CTA group ( 3.3 % ) and in 151 of 5007 ( 3.0 % ) in the functional-testing group ( adjusted hazard ratio , 1.04 ; 95 % confidence interval , 0.83 to 1.29 ; P=0.75 ) . CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing ( 3.4 % vs. 4.3 % , P=0.02 ) , although more patients in the CTA group underwent catheterization within 90 days after r and omization ( 12.2 % vs. 8.1 % ) . The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group ( 10.0 mSv vs. 11.3 mSv ) , but 32.6 % of the patients in the functional-testing group had no exposure , so the overall exposure was higher in the CTA group ( mean , 12.0 mSv vs. 10.1 mSv ; P<0.001 ) . CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing , a strategy of initial CTA , as compared with functional testing , did not improve clinical outcomes over a median follow-up of 2 years . ( Funded by the National Heart , Lung , and Blood Institute ; PROMISE Clinical Trials.gov number , NCT01174550 . ) OBJECTIVES The purpose of this study was to compare the efficiency , cost , and safety of a diagnostic strategy employing early coronary computed tomographic angiography ( CCTA ) to a strategy employing rest-stress myocardial perfusion imaging ( MPI ) in the evaluation of acute low-risk chest pain . BACKGROUND In the United States , > 8 million patients require emergency department evaluation for acute chest pain annually at an estimated diagnostic cost of > $ 10 billion . METHODS This multicenter , r and omized clinical trial in 16 emergency departments ran between June 2007 and November 2008 . Patients were r and omly allocated to CCTA ( n = 361 ) or MPI ( n = 338 ) as the index noninvasive test . The primary outcome was time to diagnosis ; the secondary outcomes were emergency department costs of care and safety , defined as freedom from major adverse cardiac events in patients with normal index tests , including 6-month follow-up . RESULTS The CCTA result ed in a 54 % reduction in time to diagnosis compared with MPI ( median 2.9 h [ 25th to 75th percentile : 2.1 to 4.0 h ] vs. 6.3 h [ 25th to 75th percentile : 4.2 to 19.0 h ] , p < 0.0001 ) . Costs of care were 38 % lower compared with st and ard ( median $ 2,137 [ 25th to 75th percentile : $ 1,660 to $ 3,077 ] vs. $ 3,458 [ 25th to 75th percentile : $ 2,900 to $ 4,297 ] , p < 0.0001 ) . The diagnostic strategies had no difference in major adverse cardiac events after normal index testing ( 0.8 % in the CCTA arm vs. 0.4 % in the MPI arm , p = 0.29 ) . CONCLUSIONS In emergency department acute , low-risk chest pain patients , the use of CCTA results in more rapid and cost-efficient safe diagnosis than rest-stress MPI . Further studies comparing CCTA to other diagnostic strategies are needed to optimize evaluation of specific patient subsets . ( Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment [ CT-STAT ] ; NCT00468325 ) STUDY OBJECTIVE Three large , multicenter , r and omized , clinical trials have shown that coronary computed tomography ( CT ) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department ( ED ) . We report 1-year event rates and re source use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial . METHODS Patients with low- to intermediate-risk chest pain and presenting to the ED were r and omized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care . Subjects were contacted by telephone at least 1 year after ED presentation . Medical record review was performed for all cardiac hospitalizations , procedures and diagnostic tests , and adverse cardiac events . Our main outcome was the composite of cardiac death and myocardial infa rct ion within 1 year . The secondary outcome was re source use . RESULTS One thous and three hundred sixty-eight patients enrolled and 1,285 ( 94 % ) had direct participant or proxy contact at 1 year . All others had record review or death index search . From index presentation through 1 year , there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event ( 1.4 % versus 1.1 % ; difference 0.3 % ; 95 % CI -5.5 % to 6.0 % ) . From hospital discharge through 1 year , there was also no difference in ED revisits ( 36 % versus 38 % ; difference -2.1 % ; 95 % CI -7.9 % to 3.7 % ) , hospital admissions ( 16 % versus 17 % ; difference -0.9 % ; 95 % CI -6.7 % to 4.9 % ) , or subsequent cardiac testing ( 13 % versus 13 % ; difference -0.4 % ; 95 % CI -6.2 % to 5.5 % ) . One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation ( 0.16 % ; 95 % CI 0.004 % to 0.87 % ) . CONCLUSION A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased re source use during 1 year . A negative coronary CT angiography result is associated with a less than 1 % major adverse cardiac event rate during the first year after testing OBJECTIVES This study sought to compare the safety , diagnostic efficacy , and efficiency of multi-slice computed tomography ( MSCT ) with st and ard diagnostic evaluation of low-risk acute chest pain patients . BACKGROUND Over 1 million patients have emergency center evaluations for acute chest pain annually , at an estimated diagnostic cost of over $ 10 billion . Multi-slice computed tomography has a high negative predictive value for exclusion of coronary artery stenoses . METHODS We r and omized patients to MSCT ( n = 99 ) versus SOC ( n = 98 ) protocol s. The MSCT patients with minimal disease were discharged ; those with stenosis > 70 % underwent catheterization , whereas cases with intermediate lesions or non-diagnostic scans underwent stress testing . Outcomes included : safety ( freedom from major adverse events over 6 months ) , diagnostic efficacy ( clinical ly correct and definitive diagnosis ) , as well as time and cost of care . RESULTS Both approaches were completely ( 100 % ) safe . The MSCT alone immediately excluded or identified coronary disease as the source of chest pain in 75 % of patients , including 67 with normal coronary arteries and 8 with severe disease referred for invasive evaluation . The remaining 25 % of patients required stress testing , owing to intermediate severity lesions or non-diagnostic scans . During the index visit , MSCT evaluation reduced diagnostic time compared with SOC ( 3.4 h vs. 15.0 h , p < 0.001 ) and lowered costs ( 1,586 dollars vs. 1,872 dollars , p < 0.001 ) . Importantly , MSCT patients required fewer repeat evaluations for recurrent chest pain ( MSCT , 2 of 99 ( 2.0 % ) patients vs. SOC , 7 of 99 ( 7 % ) patients ; p = 0.10 ) . CONCLUSIONS Multi-slice computed tomographic coronary angiography can definitively establish or exclude coronary disease as the cause of chest pain . However , inability to determine the physiological significance of intermediate severity coronary lesions and cases with inadequate image quality are present limitations . ( Study of Coronary Artery Computed Tomography to Diagnose Emergency Chest Pain CR ; http:// clinical trials.gov/ct/show/NCT00273832?order=1 ; NCT00273832 ) BACKGROUND It is unclear whether an evaluation incorporating coronary computed tomographic angiography ( CCTA ) is more effective than st and ard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes . METHODS In this multicenter trial , we r and omly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to st and ard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012 . The primary end point was length of stay in the hospital . Secondary end points included rates of discharge from the emergency department , major adverse cardiovascular events at 28 days , and cumulative costs . Safety end points were undetected acute coronary syndromes . RESULTS The rate of acute coronary syndromes among 1000 patients with a mean ( ±SD ) age of 54±8 years ( 47 % women ) was 8 % . After early CCTA , as compared with st and ard evaluation , the mean length of stay in the hospital was reduced by 7.6 hours ( P<0.001 ) and more patients were discharged directly from the emergency department ( 47 % vs. 12 % , P<0.001 ) . There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days . After CCTA , there was more downstream testing and higher radiation exposure . The cumulative mean cost of care was similar in the CCTA group and the st and ard-evaluation group ( $ 4,289 and $ 4,060 , respectively ; P=0.65 ) . CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute coronary syndromes , incorporating CCTA into a triage strategy improved the efficiency of clinical decision making , as compared with a st and ard evaluation in the emergency department , but it result ed in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care . ( Funded by the National Heart , Lung , and Blood Institute ; ROMICAT-II Clinical Trials.gov number , NCT01084239 . ) OBJECTIVES In patients admitted on suspicion of acute coronary syndrome , with normal electrocardiogram and troponines , we evaluated the clinical impact of a Coronary CT angiography (CCTA)- strategy on referral rate for invasive coronary angiography ( ICA ) , detection of significant coronary stenoses ( positive predictive value [ PPV ] ) and subsequent revascularisations , as compared to a function-based strategy ( st and ard care ) . Secondarily we assessed intermediate term clinical events . METHODS AND RESULTS We r and omised 600 patients to a CCTA-guided strategy ( 299 patients ) or st and ard care ( 301 patients ) . In the CCTA-guided group referral for ICA required a coronary stenosis > 70 % or > 50 % in the left main , and for intermediate stenoses ( 50 - 70 % ) , a stress test was used . A significant stenosis on ICA was defined as a stenosis ≥70 % or reduced FFR ≤0.75 in intermediate stenoses ( 50 - 70 % ) . Referral rate for ICA was 17 % with CCTA vs. 12 % with st and ard care ( p=0.1 ) . ICA confirmed significant coronary artery stenoses in 12 % vs. 4 % ( p=0.001 ) , and 10 % vs. 4 % were subsequently revascularised ( p=0.005 ) . PPV for the detection of significant stenoses was 71 % with CCTA vs 36 % with st and ard care ( p=0.001 ) . Clinical events ( cardiac death , myocardial infa rct ion , unstable angina pectoris , revascularisation and readmission for chest pain ) , during 120 days of follow-up , were recorded in 8 patients ( 3 % ) in the CCTA-guided group vs. 15 patients ( 5 % ) in the st and ard care group ( p=0.1 ) . CONCLUSION In patients with recent acute-onset chest pain , a CCTA-guided diagnostic strategy improves PPV for the detection of significant coronary stenoses , and increases the frequency of revascularisations , when compared to a conventional functional approach BACKGROUND Coronary CT angiography ( CCTA ) has high sensitivity , with 3 recent r and omized trials favorably comparing CCTA to st and ard-of-care . Comparison to exercise stress ECG ( ExECG ) , the most available and least expensive st and ard-of-care worldwide , has not been systematic ally tested . METHODS CT-COMPARE was a r and omized , single-center trial of low-intermediate risk chest pain subjects undergoing CCTA or ExECG after the first negative troponin . From March 2010 to April 2011 , 562 patients r and omized to either dual- source CCTA ( n=322 ) or ExECG ( n=240 ) . Primary endpoints were diagnostic performance for ACS , and hospital cost at 30 days . Secondary endpoints were time-to-discharge , admission rates , and downstream re source utilization . RESULTS ACS occurred in 24 ( 4 % ) patients . ExECG had 213 negative studies and 27 ( 26 % ) positive studies for ACS with sensitivity of 83 % [ 95 % CI : 36 , 99.6 % ] , specificity of 91 % [ CI : 86 , 94 % ] , and ROC AUC of 0.87 [ CI : 0.70 , 1 ] . CCTA ( > 50 % stenosis considered positive ) had 288 negative studies and 18/35 ( 51 % ) positive studies with a sensitivity of 100 % [ CI : 81.5 , 100 ] , specificity of 94 % [ CI : 91.2 , 96.7 % ] , and ROC of 0.97 [ CI : 0.92 , 1.0 ; p=0.2 ] . Despite CCTA having higher odds of downstream testing ( OR 2.0 ) , 30 day per-patient cost was significantly lower for CCTA ( $ 2193 vs $ 2704 , p<0.001 ) . Length of stay for CCTA was significantly reduced ( 13.5h [ 95 % CI : 11.2 - 15.7 ] , ExECG 19.7h [ 95 % CI : 17.4 - 22.1 ] , p<0.0005 ) , which drove the reduction in cost . No patient had post-discharge cardiovascular events at 30 days . CONCLUSIONS CCTA had improved diagnostic performance compared to ExECG , combined with 35 % relative reduction in length-of-stay , and 20 % reduction in hospital costs . These data lend further evidence that CCTA is useful as a first line assessment in emergency department chest pain BACKGROUND Current guidelines suggest that , for patients at moderate risk of death from unstable coronary-artery disease , either an interventional strategy ( angiography followed by revascularisation ) or a conservative strategy ( ischaemia-driven or symptom-driven angiography ) is appropriate . We aim ed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients . METHODS We did a r and omised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes ( mean age 62 years , 38 % women ) . Patients were assigned an early intervention or conservative strategy . The antithrombin agent in both groups was enoxaparin . The co- primary endpoints were a combined rate of death , non-fatal myocardial infa rct ion , or refractory angina at 4 months ; and a combined rate of death or non-fatal myocardial infa rct ion at 1 year . Analysis was by intention to treat . FINDINGS At 4 months , 86 ( 9.6 % ) of 895 patients in the intervention group had died or had a myocardial infa rct ion or refractory angina , compared with 133 ( 14.5 % ) of 915 patients in the conservative group ( risk ratio 0.66 , 95 % CI 0.51 - 0.85 , p=0.001 ) . This difference was mainly due to a halving of refractory angina in the intervention group . Death or myocardial infa rct ion was similar in both treatment groups at 1 year ( 68 [ 7.6 % ] vs 76 [ 8.3 % ] , respectively ; risk ratio 0.91 , 95 % CI 0.67 - 1.25 , p=0.58 ) . Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy ( p<0.0001 ) . INTERPRETATION In patients presenting with unstable coronary-artery disease , an interventional strategy is preferable to a conservative strategy , mainly because of the halving of refractory or severe angina , and with no increased risk of death or myocardial infa rct ion BACKGROUND In patients with stable coronary artery disease , it remains unclear whether an initial management strategy of percutaneous coronary intervention ( PCI ) with intensive pharmacologic therapy and lifestyle intervention ( optimal medical therapy ) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events . METHODS We conducted a r and omized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers . Between 1999 and 2004 , we assigned 1149 patients to undergo PCI with optimal medical therapy ( PCI group ) and 1138 to receive optimal medical therapy alone ( medical-therapy group ) . The primary outcome was death from any cause and nonfatal myocardial infa rct ion during a follow-up period of 2.5 to 7.0 years ( median , 4.6 ) . RESULTS There were 211 primary events in the PCI group and 202 events in the medical-therapy group . The 4.6-year cumulative primary -event rates were 19.0 % in the PCI group and 18.5 % in the medical-therapy group ( hazard ratio for the PCI group , 1.05 ; 95 % confidence interval [ CI ] , 0.87 to 1.27 ; P=0.62 ) . There were no significant differences between the PCI group and the medical-therapy group in the composite of death , myocardial infa rct ion , and stroke ( 20.0 % vs. 19.5 % ; hazard ratio , 1.05 ; 95 % CI , 0.87 to 1.27 ; P=0.62 ) ; hospitalization for acute coronary syndrome ( 12.4 % vs. 11.8 % ; hazard ratio , 1.07 ; 95 % CI , 0.84 to 1.37 ; P=0.56 ) ; or myocardial infa rct ion ( 13.2 % vs. 12.3 % ; hazard ratio , 1.13 ; 95 % CI , 0.89 to 1.43 ; P=0.33 ) . CONCLUSIONS As an initial management strategy in patients with stable coronary artery disease , PCI did not reduce the risk of death , myocardial infa rct ion , or other major cardiovascular events when added to optimal medical therapy . ( Clinical Trials.gov number , NCT00007657 [ Clinical Trials.gov ] . ) Aims The objective was to examine the impact of out-of-hours exercise treadmill tests ( ETTs ) on length of hospital stay ( LOS ) for patients admitted to a chest pain assessment unit with symptoms suggestive of acute coronary syndrome . Methods Prospect i ve observational study with 30-day follow-up of low-to-intermediate-risk chest pain patients undergoing out-of-hours ETT . Eligible patients had a nonischemic ECG , normal 6–12-h ST-segment monitoring , a negative 12-h troponin T assay , and no contraindications to exercise . Observed LOS was compared to expected LOS in the absence of out-of-hours ETT , using Wilcoxon rank-sum test . Estimated bed day savings and major adverse events at 30 days after discharge were examined . Results Four hundred and twenty-two patients with a mean age of 52 years ( SD 13 years , 25–83 years ) were evaluated . Fifty-two per cent ( n = 221 ) were men ; 66 % ( n = 279 ) had one or less cardiovascular risk factors ; and 79 % ( n = 334 ) of the patients presented on a Friday or Saturday . ETT was performed on a weekend day in 86 % ( n = 363 ) of the patients , facilitating same-day discharges in 71 % ( n = 300 ) . The median LOS ( interquartile range ) was 1 day ( 1 , 2 days ) for patients assessed with out-of-hours ETT . The expected median LOS ( IQR ) was 3 days ( 2 , 4 days ) ( P < 0.05 ) in the absence of out-of-hours ETT . Each out-of-hours ETT was estimated to save a mean ( SD , range ) of 1.6 ( 0.6 , 1–4 ) bed days . Thirty-day mortality and readmission rates were 0 and 0.2 % ( 1 of 422 ) , respectively . Conclusion The availability of out-of-hours ETT facilitates safe early discharge and reduced LOS for low-to-moderate-risk patients admitted with symptoms of acute coronary syndrome |
11,101 | 29,444,366 | The available studies revealed inconsistencies , but the majority indicated that obesity is associated with AD .
Studies addressing obesity in infancy or early childhood ( age < 2 years ) and AD reported a positive association .
In Conclusion , overweight/obesity is associated with an increased risk of AD . | Obesity has been associated with atopic dermatitis ( AD ) ; however , the results have been conflicting .
Our aim was to provide an up date on current knowledge from observational studies addressing the possible association between obesity and AD . | The purpose of this study was to estimate the national prevalence of childhood asthma and other allergic diseases in Korea , and to determine potential risk factors for the diseases . Stratified r and om sample s of 42,886 were selected from 34 elementary ( 6 - 12 yr olds ) and 34 middle schools ( 12 - 15 yr olds ) nationwide , and 38,955 were in the final analysis . The Korean-translated modified version of the International Study of Asthma and Allergies in Childhood question naire was used in this cross-sectional survey . Twelve-month prevalences of the symptoms of asthma , rhinoconjunctivitis , and flexural eczema were 8.7 % , 10.5 % , 7.3 % in 6 - 12 yr olds , and 8.2 % , 10.0 % , 3.9 % in 12 - 15 yr olds , respectively . For allergic conjunctivitis , food allergy , and drug allergy , the prevalences in 6 - 12 yr olds were 11.2 % , 6.5 % , and 1.5 % , respectively . Asthma and flexural eczema decreased significantly with age . Other significant risk factors were also noted . For 6 - 12 yr-old asthma , adjusted odds ratio ( aOR ) of body mass index was 1.21 with 95 % confidence interval ( CI ) 1.0 - 1.48 , aOR of passive smoking was 1.37 with 95%CI 1.24 - 1.51 , aOR of carpet use was 1.28 with 95%CI 1.10 - 1.49 . For 6 - 12 yr-old eczema , aOR of affluence was 1.22 with 95%CI 1.07 - 1.39 . The control of obesity and passive smoking would be the most important preventive measures of allergic diseases BACKGROUND A positive association between body mass index ( BMI ) and allergic diseases has recently been suggested ; however the sex-dependence of this association remains controversial . The aim of the present study was to explore the relationship between BMI and asthma and eczema , as well as its sex-dependence in young adolescents . METHODS Self-reported data obtained through the st and ardized International Study of Asthma and Allergies in Childhood ( ISAAC ) Phase Three written question naires of 2926 young adolescents aged 13 - 14 years old from r and omly selected schools in Skopje ( Republic of Macedonia ) were used . The BMI for each individual was calculated and used-both unadjusted and adjusted for confounding factors-as a variable for analysis . The international cut-off points for BMI for overweight and obesity by sex and age were used . Because of the very low prevalence of obesity ( 1.5 % ) , obese respondents were included in the overweight group . The data were statistically analyzed by the chi-square test , the t-test for independent sample s and odds ratios ( OR , 95 % CI ) in binary logistic regression . RESULTS Being overweight was significantly associated with an increased risk of having a dry night cough without a cold or chest infection ( adjusted OR : 1.54 ; 95 % CI : 1.09 - 2.16 ; p = 0.01 ) and with having had self-reported asthma at some time ( adjusted OR : 2.36 ; 95 % CI : 1.02 - 5.44 ; p = 0.04 ) in boys only . A significant association between overweight and other symptoms of asthma or atopic eczema was not established . CONCLUSION These findings suggest a male-specific positive association between overweight and a current dry night cough and having received a diagnosis of asthma at some time . No association was found with other asthma symptoms or atopic eczema in young adolescents Background The prevalence of allergic diseases such as asthma , allergic rhinitis and atopic dermatitis is increasing rapidly worldwide , especially among children and in western countries . This coincides with an increase in body mass index ( BMI ) , which might be a major risk factor for atopic diseases . Objectives To study the relationship between high BMI and allergic diseases , as well as skin-prick test ( SPT ) positivity and exercise-induced asthma ( EIA ) in 6733 r and omly selected schoolchildren aged 9–11 years in the French Six Cities Study . Methods A cross-sectional study was carried out in Bordeaux , Clermont-Ferr and , Créteil , Marseille , Reims and Strasbourg . Parental question naires based on the International Study on Asthma and Allergies in Childhood ( ISAAC ) were used to collect information on allergic diseases and potential risk factors . Skin-prick testing to common allergens was performed to identify the existence of an allergic hypersensitivity and an exercise test was also performed to assess EIA . Height and weight were collected by trained investigators . After computing the BMI ( weight/height squared ) , the International Obesity Task Force ( IOTF ) cut-offs were used to define overweight and obesity . The children were also classified as wheezing or non-wheezing . Results After adjustment for confounding factors , lifetime asthma was associated with high BMI among non-wheezing children ( adjusted OR , aOR=1.98 , 95 % CI ( 1.06 to 3.70 ) ) . In addition , lifetime and past-year allergic rhinitis was associated with high BMI in wheezing children ( aOR=1.63 , ( 1.09 to 2.45 ) and aOR=2.20 , ( 1.13 to 4.27 ) ) . However , high BMI was not significantly associated with eczema , SPT positivity or EIA . Conclusions This study shows a positive association between high BMI and lifetime asthma in non-wheezing children . High BMI was also associated with lifetime and past-year allergic rhinitis . Further studies are needed to provide causal evidence Leptin is a pleiotropic hormone believed to regulate body weight . Its function in wasting during inflammatory disease in humans is unknown . We studied the effect of repeated tumor necrosis factor ( TNF ) infusion on serum leptin levels in six patients with solid tumors . TNF infusion on day 1 result ed in an increase in serum leptin levels from 3.1 ( SEM + /- 0.28 ) ng/mL to 5.2 ( SEM + /- 0.6 ) ng/mL after 12 h ( P < 0.001 ) . The serum levels returned to baseline within 24 h. Similar results were obtained when TNF was infused on subsequent days . The study shows that leptin serum levels are under control of TNF Background Childhood obesity and asthma are increasing worldwide . A possible link between the two conditions has been postulated . Methods Cross-sectional studies of stratified r and om sample s of 8–12-year-old children ( n = 10 652 ) ( 16 centres in affluent and 8 centres in non-affluent countries ) used the st and ardized methodology of ISAAC Phase Two . Respiratory and allergic symptoms were ascertained by parental question naires . Tests for allergic disease were performed . Height and weight were measured , and overweight and obesity were defined according to international definitions . Prevalence rates and prevalence odds ratios were calculated . Results Overweight ( odds ratio = 1.14 , 95%-confidence interval : 0.98 ; 1.33 ) and obesity ( odds ratio = 1.67 , 95%-confidence interval : 1.25 ; 2.21 ) were related to wheeze . The relationship was stronger in affluent than in non-affluent centres . Similar results were found for cough and phlegm , rhinitis and eczema but the associations were mostly driven by children with wheeze . There was a clear association of overweight and obesity with airways obstruction ( change in FEV1/FVC , −0.90 , 95%-confidence interval : −1.33 % ; −0.47 % , for overweight and −2.46 % , 95%-confidence interval : −3.84 % ; −1.07 % , for obesity ) whereas the results for the other objective markers , including atopy , were null . Conclusions Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries . Moreover , body mass index is associated with an objective marker of airways obstruction ( FEV1/FVC ) but no other objective markers of respiratory and allergic disorders Objective To investigate trends in obesity prevalence in recent years and to predict the obesity prevalence in 2015 in European population s. Methods Data of 97 942 participants from seven cohorts involved in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study participating in the Diogenes project ( named as “ Diogenes cohort ” in the following ) with weight measurements at baseline and follow-up were used to predict future obesity prevalence with logistic linear and non-linear ( leveling off ) regression models . In addition , linear and leveling off models were fitted to the EPIC-Potsdam data set with five weight measures during the observation period to find out which of these two models might provide the more realistic prediction . Results During a mean follow-up period of 6 years , the obesity prevalence in the Diogenes cohort increased from 13 % to 17 % . The linear prediction model predicted an overall obesity prevalence of about 30 % in 2015 , whereas the leveling off model predicted a prevalence of about 20 % . In the EPIC-Potsdam cohort , the shape of obesity trend favors a leveling off model among men ( R2 = 0.98 ) , and a linear model among women ( R2 = 0.99 ) . Conclusion Our data show an increase in obesity prevalence since the 1990ies , and predictions by 2015 suggests a sizeable further increase in European population s. However , the estimates from the leveling off model were considerably lower Background Atopic dermatitis ( AD ) prevalence has considerably increased worldwide in recent years . Study ing indoor environments is particularly relevant , especially in industrialised countries where many people spend 80 % of their time at home , particularly children . This study is aim ed to identify the potential association between AD and the energy source ( biomass , gas and electricity ) used for cooking and domestic heating in a Spanish schoolchildren population . Methods As part of the ISAAC ( International Study of Asthma and Allergies in Childhood ) phase III study , a cross-sectional population -based survey was conducted with 21,355 6-to-7-year-old children from 8 Spanish ISAAC centres . AD prevalence , environmental risk factors and the use of domestic heating/cooking devices were assessed using the vali date d ISAAC question naire . Crude and adjusted odds ratios ( cOR , aOR ) and 95 % confidence intervals ( CIs ) were obtained . A logistic regression analysis was performed ( Chi-square test , p-value < 0.05 ) . Results It was found that the use of biomass systems gave the highest cORs , but only electric cookers showed a significant cOR of 1.14 ( 95 % CI : 1.01 - 1.27 ) . When the geographical area and the mother ’s educational level were included in the logistic model , the obtained aOR values differed moderately from the initial cORs . Electric heating was the only type which obtained a significant aOR ( 1.13 ; 95 % CI : 1.00 - 1.27 ) . Finally , the model with all selected confounding variables ( sex , BMI , number of siblings , mother ’s educational level , smoking habits of parents , truck traffic and geographical area ) , showed aOR values which were very similar to those obtained in the previous adjusted logistic analysis . None of the results was statistically significant , but the use of electric heating showed an aOR close to significance ( 1.14 ; 95 % CI : 0.99 - 1.31 ) . Conclusion In our study population , no statistically significant associations were found between the type of indoor energy sources used and the presence of AD Abstract Background Atopic diseases including asthma , rhinitis and eczema have increased in the second half of the past century . This has been well studied among children and adolescents but with the exception of asthma to a much lesser extent in adults . The adult risk factor pattern of atopic diseases , in particular of eczema , and their relation to allergic sensitization are yet to be fully eluci date d. Studies among adults that have compared the risk factor pattern for these conditions in the same material are very few . The objective of this study was to compare the risk factor patterns for asthma , rhinitis and eczema in a r and omly selected adult population . Methods A question naire survey on atopic diseases was dispatched by mail to 30,000 r and omly selected individuals in West Sweden aged 16–75 years and 62 % participated . A subgroup of 2000 individuals was selected for clinical examinations including blood sampling for specific serum Immunoglobulin E to common airborne allergens and 1172 attended . Results The prevalence of current asthma was 11.8 % , current rhinitis 42.8 % , current eczema 13.5 and 2.3 % had all three conditions while 13.9 % had at least two conditions . No mutual risk factor was identified for all three conditions . Allergic sensitization was a strong risk factor for current asthma ( OR 4.1 CI 2.7–6.3 ) and current rhinitis ( OR 5.1 CI 3.8–6.9 ) but not so for current eczema . Obesity was a risk factor for current asthma and current rhinitis , while farm childhood decreased the risk for current asthma and current rhinitis . Occupational exposure to gas dust or fumes and female sex was associated with an increased risk of current asthma and current eczema . Conclusions There are different risk factor patterns for asthma , rhinitis and eczema in adults but some risk factors are overlapping between some of the conditions . The effect of mutable risk factors should be assessed further in longitudinal studies BACKGROUND Early nutrition and adiposity have been linked to atopic dermatitis ( AD ) development . OBJECTIVE We sought to describe risk factors for AD in the first year of life in infants participating in the Cork BASELINE birth cohort study ( n = 1537 ) . METHODS Prospect i ve data on early-life events , infant feeding , and nutritional and environmental exposures were collected at 15 weeks ' gestation , birth , and 2 , 6 , and 12 months of age . Body composition was assessed by using air displacement plethysmography at day 2 and 2 months . The primary outcome , persistent AD , was determined if the U.K. Working Party Diagnostic Criteria were satisfied at both 6 and 12 months . RESULTS At 6 and 12 months , the point prevalence of AD was 14.2 % ( 99 % CI , 10.5 % to 17.8 % ) and 13.7 % ( 99 % CI , 10.3 % to 17.6 % ) , respectively ; 7.5 % ( 99 % CI , 5.0 % to 9.9 % ) of infants had AD at both 6 and 12 months of age . At hospital discharge , 35 % of infants were exclusively breast-fed , decreasing to 14 % by 2 months . Complementary feeding was commenced at a median of 19 weeks ( interquartile range , 17 - 22 weeks ; 19 % at < 17 weeks and 6 % at ≥26 weeks ) . Median fat mass at day 2 was 0.35 kg ( interquartile range , 0.25 - 0.48 kg ) . A parental history of atopic disease was self-reported by 43 % of mothers and 34 % of fathers . Risk factors for AD at 6 and 12 months were maternal atopy ( adjusted odds ratio , 2.99 ; 99 % CI , 1.35 - 6.59 ; P = .0004 ) and fat mass of the 80th percentile or greater at day 2 ( adjusted odds ratio , 2.31 ; 99 % CI , 1.02 - 2.25 ; P = .009 ) . CONCLUSION This is the first report of neonatal adiposity as a predictor of AD at 6 and 12 months of age in a well-characterized atopic disease-specific birth cohort BACKGROUND The influence of nutrition on the physiological functions of man is well studied . Numerous diseases can be exacerbated by obesity . However , it has not yet been determined whether body weight and body mass index ( BMI ) , as an indicator of a high body fat store , can influence skin sensitivity . OBJECTIVE This study investigates the correlation between body mass index and the epidermal functions , evaluated by bioengineering methods , before and after an irritant patch test with sodium lauryl sulphate ( SLS ) . METHODS Epidermal functions were evaluated using an evaporimeter , chromameter and laser-Doppler-flowmeter . Patch testing was conducted for 48 h with two different concentrations of SLS ( 0.25 % and 0.5 % ) on the forearms of healthy volunteers . Measurements were performed 24h after patch removal . RESULTS Obese individuals showed significantly increased transepidermal water loss ( TEWL ) , skin blood flow and skin colour ( red ) as compared to a control group . However , the degree of skin sensitivity to SLS was not correlated with BMI . CONCLUSION Basal biophysical parameters of the skin are primarily correlated with the BMI . This may be caused by obesity-induced physiological changes , e.g. increased sweat gl and activity , high blood pressure and physiological temperature-regulating system . The epidermal barrier function , as evaluated after SLS patch testing is , however , not correlated with a high BMI , indicating a normal skin barrier Objective : We aim ed to assess increased birth weight or birth length in relation to allergic diseases at 4 years of age , taking body mass index ( BMI ) at age 4 as a covariate in the adjustment . Methods : The parents of a large prospect i ve birth cohort answered question naires on environmental factors and allergic symptoms when their children were 2 months and 1 , 2 and 4 years old . Perinatal data on weight and length at birth were received from the child care health centres . The children were clinical ly examined at 4 years of age and height and weight recorded . Blood was drawn for analysis of specific IgE antibodies to common inhalant allergens . Risk associations between birth anthropometric measures and wheeze , allergic diseases or sensitisation were estimated in multivariate logistic regression analyses ( n = 2869 ) . Results : There were no clear overall associations between birth weight and allergic diseases at 4 years of age . Birth length ⩾90th percentile was inversely associated with any wheeze at age 4 ( adjusted OR 0.64 , 95 % CI 0.44 to 0.92 ) but was significantly associated only with late-onset wheeze ( adjusted OR 0.40 , 95 % CI 0.21 to 0.77 ) . No such associations were seen for persistent or transient wheeze , eczema , rhinitis or allergic sensitisation . Transient wheeze during the first 2 years of age tended to be associated with increased BMI at age 4 . Conclusion : Increased birth weight was not associated with wheeze or allergic disease . Increased birth length may play a protective role in late-onset wheeze in early childhood BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders BACKGROUND Developmental status at birth and subsequent obesity have been implicated in the development of childhood atopic dermatitis ( AD ) and allergic rhinitis ( AR ) . METHODS The current study analysed the cohort data of 74 688 junior high school students from a national retrospective birth cohort study in Taiwan . A r and om 10 % sample was selected from singleton livebirths with complete data on the analytical variables of interest . Atopic disorders , including AD and AR , were assessed by question naires ( International Study of Asthma and Allergies in Childhood ) . Logistic regression analyses were applied with adjustments for related risk factors . RESULTS Among subjects mainly 13 - 15 years of age , the estimated prevalence was 7.6 % for AD and 22.4 % for AR . While the role of fetal growth in allergic disorders was less evident , the risk of developing AD and AR were both influenced by a combination of fetal growth status and adolescent body mass index ( BMI ) . Compared with those with normal fetal growth and school-aged BMI , the risk of developing AD increased 64 % among adolescents with both restricted fetal growth and high BMI ( odds ratio 1.64 , 95 % confidence interval 1.37 , 1.97 ) . The risk for this combination was higher than that for either restricted fetal growth or high BMI alone . Nevertheless , the overall interaction between BMI and fetal growth status on atopic disorders did not reach statistical significance . CONCLUSIONS Excessive weight gain could be an important risk factor related to developing atopic dermatitis and allergic rhinitis during adolescence , especially among infants born small for gestational age BACKGROUND Obesity in children is associated with increased asthma and atopy . OBJECTIVE We sought to determine whether obesity in childhood or adolescence increases the risk of atopic dermatitis . METHODS This retrospective , practice -based , case-control study r and omly sample d 414 children and adolescents ( age , 1 - 21 years ) with atopic dermatitis between January 2000 and December 2007 and 828 r and omly sample d healthy control subjects . Information was obtained from an electronic medical record . Observations were made before the a priori hypothesis . RESULTS Obesity in children is associated with increased atopic dermatitis ( conditional logistic regression : odds ratio , 2.00 ; 95 % CI , 1.22 - 3.26 ; P = .006 ) . These atopic dermatitis-predisposing effects are found when obesity started by less than 2 years of age ( adjusted odds ratio [ aOR ] , 15.10 ; 95 % CI , 1.51 - 151.21 ; P = .02 ) and 2 to 5 years ( aOR , 2.58 ; 95 % CI , 1.24 - 5.41 ; P = .01 ) but not greater than 5 years ( aOR , 1.32 ; 95 % CI , 0.66 - 2.64 ; P = .43 ) and when obesity was prolonged for 2.5 to 5 years ( aOR , 2.64 ; 95 % CI , 1.13 - 6.18 ; P = .03 ) and greater than 5 years ( aOR , 3.40 ; 95 % CI , 1.34 - 8.63 ; P = 0.01 ) . Obesity is associated with more severe atopic dermatitis ( ordinal logistic regression : aOR , 2.37 ; 95 % CI , 1.24 - 5.37 ; P = .01 ) . Obese children who eventually have atopic dermatitis require more frequent pediatrician visits for the management of atopic dermatitis ( ordinal logistic regression : aOR , 2.22 ; 95 % CI , 1.12 - 4.50 ; P = .03 ) . CONCLUSION Prolonged obesity in early childhood is a risk factor for atopic dermatitis . Weight loss might be an important approach for the prevention and treatment of atopic dermatitis in children BACKGROUND Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence -based guidelines , it is often justified by the belief in a subgroup effect in individuals developing atopic disease . We aim ed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction , atopic eczema , or allergic sensitisation . METHODS In the r and omised , double-blind , multicentre Bronchiolitis ALL trial , 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay . R and omisation was done central ly , and the two study medications ( 20 mg/mL racemic epinephrine or 0.9 % saline ) were prepared in identical bottles . The dose given depended on the infant 's weight : 0.10 mL , less than 5 kg ; 0.15 mL , 5 - 6.9 kg ; 0.2 mL , 7 - 9.9 kg ; and 0.25 mL , 10 kg or more ; all dissolved in 2 mL of 0.9 % saline before nebulisation . The primary outcome was the length of hospital stay . In this follow-up study , 294 children were reinvestigated at 2 years of age with an interview , a clinical examination , and a skin prick test for 17 allergens , determining bronchial obstruction , atopic eczema , and allergic sensitisation , on which subgroup analyses were done . Analyses were done by intention to treat . The trial has been completed and is registered at Clinical Trials.gov ( number NCT00817466 ) and EUDRACT ( number 2009 - 012667 - 34 ) . FINDINGS Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years ( 143 [ 48.6 % ] of 294 patients ; p(interaction)=0.40 ) . However , the presence of atopic eczema or allergic sensitisation by the age of 2 years ( n=77 ) significantly interacted with the treatment effect of inhaled epinephrine ( p(interaction)=0.02 ) ; the length of stay ( mean 80.3 h , 95 % CI 72.8 - 87.9 ) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years ( -19.9 h , -33.1 to -6.3 ; p=0.003 ) . No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years ( + 16.2 h , -11.0 to 43.3 ; p=0.24 ) . INTERPRETATION Contrary to our hypothesis , hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema , allergic sensitisation , or recurrent bronchial obstruction . The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases . FUNDING Medicines for Children Network , Norway |
11,102 | 25,271,211 | As perpetrators , the overall effects for NMEs were much less pronounced , compared with when they served as victims . | The aim of the present work was to perform a systematic review of drug metabolism , transport , pharmacokinetics , and DDI data available in the NDAs approved by the FDA in 2013 , using the University of Washington Drug Interaction Data base , and to highlight significant findings . | Macitentan is a dual endothelin receptor antagonist under phase 3 investigation in pulmonary arterial hypertension . We investigated the effect of cyclosporine ( Cs ) and rifampin on the pharmacokinetics of macitentan and its metabolites ACT-132577 and ACT-373898 in healthy male subjects . In addition , in vitro studies were performed to investigate interactions between macitentan and its active metabolite ACT-132577 with human organic anion-transporting polypeptides ( OATPs ) . The clinical study ( AC-055 - 111 ) was conducted as a two-part , one-sequence , crossover study . Ten subjects in each part received multiple-dose macitentan followed by multiple-dose co-administration of Cs ( part A ) or rifampin ( part B ) . In the presence of Cs , steady-state area under the plasma concentration – time profiles during a dose interval ( AUCτ ) for macitentan and ACT-373898 increased 10 % and 7 % , respectively , and decreased 3 % for ACT-132577 . Steady-state AUCτ of macitentan and ACT-373898 in the presence of rifampin decreased 79 % and 64 % , respectively . For ACT-132577 , no relevant difference in AUCτ between the two treatments was observed . Macitentan co-administered with Cs or rifampin was well tolerated . The complementary in vitro studies demonstrated no marked differences in uptake rates of macitentan and ACT-132577 between the wild-type and OATP over-expressing cells over the concentration range tested . Concomitant treatment with Cs did not have any clinical ly relevant effect on the exposure to macitentan or its metabolites , at steady-state . Concomitant treatment with rifampin reduced significantly the exposure to macitentan and its metabolite ACT-373898 at steady-state but did not affect the exposure to the active metabolite ACT-132577 to a clinical ly relevant extent OBJECTIVE To investigate the effect of eslicarbazepine acetate ( ESL ) on the pharmacokinetics of simvastatin ( SMV ) , a known CYP3A4 substrate , in healthy subjects . METHODS Single centre , two-way cross-over , r and omized , open-label study in 24 healthy volunteers . The volunteers received an oral single-dose of SMV 80 mg on two occasions ( once administered alone and once after treatment with an oral once-daily dose of 800 mg of ESL for 14 days ) , separated by a wash-out period of 3 weeks or more . The analysis of variance ( ANOVA ) was used to test for differences between Test ( SMV under co-administration with ESL ) and Reference ( SMV administered alone ) treatments for AUC0-∞ , AUC0-t and Cmax of SMV and SMV-acid . RESULTS Mean systemic exposure ( AUC ) measurements for both SMV and SMV-β-hydroxyacid ( SMV-acid ) were up to 54 % lower during ESL use . The Test/Reference geometric mean ratios ( GMR ) ( 90 % CI ) for the AUC0-t of SMV and SMV-acid were 46 % ( 38 % ; 55 % ) and 49 % ( 44 % ; 55 % ) , respectively . Mean peak concentrations ( Cmax ) of both SMV and SMV-acid were reduced by 60 % and 41 % , respectively , when SMV was administered with ESL . CONCLUSIONS A significant effect of repeated ESL administration on the pharmacokinetics of SMV and its metabolite SMV-acid was observed . Therefore , dose adjustment of SMV may be required when used concomitantly with ESL , if a clinical ly significant change in lipids is noted |
11,103 | 22,412,976 | Conclusion This meta- analysis demonstrates that postoperative visual performance with blue light-filtering IOLs is approximately equal to that of UV light-filtering IOLs after cataract surgery , but color vision with blue light-filtering IOLs demonstrated some compromise in the blue light spectrum under mesopic light conditions | Background A number of published r and omized controlled trials have been conducted to evaluate visual performance of blue light-filtering intraocular lenses ( IOL ) and UV light-filtering intraocular lenses ( IOL ) after cataract phacoemulsification surgery .
However , results have not always been consistent .
Therefore , we carried out a meta- analysis to compare the effectiveness of blue light-filtering IOLs versus UV light-filtering IOLs in cataract surgery . | PURPOSE To compare contrast acuity at different illumination levels and color vision and the subjective impression in patients after bilateral cataract surgery with a mixed implantation of a blue-light-filtering and an ultraviolet (UV)-filtering intraocular lens ( IOL ) . DESIGN R and omized , controlled , double-masked , and bilateral study with intraindividual comparison . PARTICIPANTS This study included 48 eyes of 24 consecutive patients with age-related cataract . METHODS Each patient had st and ardized small incision cataract surgery with IOL implantation into the capsular bag . Patients were r and omly assigned to receive a blue-light-filtering Hoya AF-1 ( UY ) YA-60BB IOL in one eye and a UV-filtering Hoya AF-1 ( UV ) VA-60BB IOL ( Hoya Medical Europe , Frankfurt/Main , Germany ) in the contralateral eye . Contrast acuity was measured at illumination levels of 500 , 5 , and 0.5 lux and contrast levels of 100 % , 50 % , 25 % , 12.5 % , and 6.25 % . Color vision was assessed using the Lanthony desaturated D-15 test , the Lanthony new color test ( Munsell chroma 2 and 4 ) , and an anomaloscope . Blue/yellow foveal threshold was tested applying short-wave automated perimetry . The subjective visual impression of patients was evaluated using a question naire . MAIN OUTCOME MEASURES Contrast acuity , color vision , and foveal threshold . RESULTS The blue-light-filtering IOLs had worse contrast acuity ( P = 0.0004 ) and foveal threshold ( P = 0.008 ) compared with the UV-filtering IOLs . Color vision tests and high-contrast visual acuity did not show any statistically significant differences between IOLs ( P>0.05 ) . On question ing , 3 of 24 patients noticed a difference between the implanted IOLs concerning visual impression . CONCLUSIONS This study shows that blue-light-filtering IOLs negatively affect contrast acuity and blue/yellow foveal threshold when compared with UV-filtering IOLs . Although the differences were small , the results suggest bilateral implantation of the same IOL type and avoidance of a mixed implantation of a blue-light-filtering IOL in one and a non-blue-light-filtering IOL in the contralateral eye in patients with high dem and s in color vision . FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article PURPOSE : To compare best distance visual acuity , color perception , and contrast sensitivity between eyes with an AcrySof Natural intraocular lens ( IOL ) ( Alcon Laboratories Inc. ) and fellow eye with an AcrySof IOL and to compare results in the IOL groups to those in normal , similarly aged patients with clear phakic eyes . SETTING : Sri Sankaradeva Nethralaya , Guwahati , India . METHODS : This prospect i ve r and omized parallel group single‐center patient‐masked examiner‐masked study comprised 26 eyes of 13 healthy patients with bilateral age‐related cataract . All patients had cataract surgery by phacoemulsification in both eyes ; 1 eye received an AcrySof Natural IOL ( SN60AT ) and the fellow eye , an AcrySof ( SA60AT ) IOL . Final postoperative examination was performed at the end of 18 months . In addition to other findings , visual acuity , color perception , and contrast sensitivity were recorded . A group of normal , similarly aged phakic individuals with clear lenses was examined for contrast sensitivity . The records thus obtained were analyzed statistically . RESULTS : The AcrySof and AcrySof Natural IOL groups had a statistically significant improvement in visual acuity and color perception in comparison to preoperative status , and this was maintained until the last postoperative follow‐up at 18 months . There was no statistically significant difference in the findings between the 2 IOL groups . The AcrySof and the AcrySof Natural IOL groups showed significant improvement in contrast sensitivity from the preoperative to the postoperative period ( both P<.001 ) . However , the AcrySof Natural IOL group was better than the AcrySof IOL group when each group was compared separately to similarly aged phakic individuals with clear lenses . CONCLUSIONS : Pseudophakia following AcrySof Natural SN60AT and AcrySof SA60AT IOL implantation led to equivalent visual acuity and color perception . But the contrast sensitivity in the AcrySof Natural group was better and near normal in reference to a healthy , age‐matched control group PURPOSE To study colour vision and retinal nerve fibre layer ( RNFL ) photographs in patients with an Acrysof Natural intraocular lens ( IOL ) . METHODS We carried out a r and omized double-blind study . An Acrysof Natural IOL ( model SN60AT ) was implanted in 25 eyes of 19 patients and an Acrysof IOL ( model SA60AT ) was implanted in 27 eyes of 18 control patients . The patients returned for colour vision tests and fundus photography 1 - 6 months after the surgery . RESULTS St and ard pseudoisochromatic plates , part 2 , were correctly interpreted and the Farnsworth-Munsell 100-hue test ( FM 100 ) total and individual box scores were normal in all IOL eyes . In the FM 100 hue test there were no significant differences in the results of the total error scores or the error scores of the individual boxes between the eyes with Acrysof Natural and those with Acrysof lenses . The yellow coloration of the Acrysof Natural IOL did not affect the visibility of the RNFL in photographs . CONCLUSIONS The Acrysof Natural IOL did not affect colour vision in the tested patients , even in the blue region of the spectrum , and can be implanted in patients who need to have normal colour vision for the purpose s of their occupation . The Acrysof Natural IOL does not interfere with RNFL photography and can also be used in patients with glaucoma PURPOSE To compare postoperative best distance visual acuity ( VA ) , contrast sensitivity and colour perception with the blue light-filtering AcrySof Natural ( SN60AT ) and AcrySof single-piece ( SA60AT ) intraocular lenses ( IOLs ) . METHODS This was a prospect i ve , r and omized , comparative , interventional study comparing postoperative performance between the SN60 and SA60 IOLs . There were nine patients ( nine eyes ) in the SN60 group and 10 patients ( 10 eyes ) in the SA60 group . All patients were operated using phacoemulsification . Postoperative VA ( Snellen chart ) , contrast sensitivity ( Pelli-Robson contrast sensitivity chart ) and colour perception ( Farnsworth-Munsell D-15 panel test ) were measured at 1 , 3 and 6 months postoperatively . RESULTS Postoperative best corrected VA after 6 months was 20/20 or better in 89 % of SN60 eyes and 100 % of SA60 eyes . Postoperative contrast sensitivity scores improved significantly in both groups under both photopic and mesopic conditions . There were no statistically significant differences in contrast sensitivity scores between the SN60 and SA60 groups at any of the postoperative evaluation time-points . Postoperative colour perception improved significantly in both the SN60 and SA60 groups , and there were no statistically significant differences in colour perception performance between the two groups . CONCLUSION The blue light-filtering AcrySof Natural ( SN60 ) IOL has postoperative visual performance comparable with that of the AcrySof single-piece ( SA60 ) IOL PURPOSE : To evaluate the effect of blue‐light‐filtering intraocular lenses ( IOLs ) with a yellow chromophore on color contrast sensitivity by intraindividual comparison with an identically design ed IOL without a blue‐light filter . SETTING : Medical University of Vienna , Department of Ophthalmology , Vienna , Austria . METHODS : R and omized implantation of an AF‐1 ( UV ) IOL ( Hoya ) in 1 eye and an AF‐1 ( UY ) IOL ( Hoya ) in the contralateral eye was performed after phacoemulsification and primary posterior curvilinear capsulorhexis . Three months postoperatively , the best distance‐corrected visual acuity was evaluated . Before color contrast sensitivity testing , a heterochromatic flicker test was performed in both eyes to avoid error in brightness matching . Central and peripheral tritan color contrast sensitivities were evaluated using the Moorfields Vision System ( CH Electronics ) . RESULTS : Visual acuity did not differ significantly between the 2 IOL groups ( P>.05 ) . The central color contrast sensitivity threshold also did not differ significantly between eyes with a clear IOL and eyes with a yellow IOL at any tested spatial frequency . The peripheral color contrast sensitivity test showed slightly higher color contrast sensitivity thresholds in eyes with a yellow IOL , although the differences were not statistically significant . Two patients independently reported subjective changes in color perception in the eye with the yellow IOL . CONCLUSION : In this intraindividual comparison , the implantation of a blue‐light‐filtering IOL did not lead to a clinical ly significant change in color contrast sensitivity PURPOSE : To evaluate the results of the first blue light – filtering photochromic intraocular lens ( IOL ) and compare them with those of a regular yellow blue light – filtering IOL and a clear ultraviolet‐filtering IOL in human eyes under various lighting conditions . SETTING : Beijing Tongren Eye Center , Beijing Tongren Hospital , Capital Medical University ; Beijing Ophthalmology & Visual Sciences Key Laboratory , Beijing , China . DESIGN : Prospect i ve comparative clinical study . METHODS : This study evaluated eyes that had implantation of 1 of the following 3 IOLs : photochromic Aurium Matrix acrylic , model 400 ; yellow AF‐1 ( UY ) ; or clear MC611MI . All eyes were followed for 3 months . The uncorrected ( UDVA ) and corrected ( CDVA ) distance visual acuities , contrast vision ( lighting 400 lux , 30 lux , 5 lux ) , contrast sensitivity , color vision ( Farnsworth‐Munsell 100‐hue test under 400 lux , 30 lux ) , and patient question naire responses were evaluated . RESULTS : The photochromic IOL group comprised 39 eyes ; the yellow IOL group , 41 eyes ; and the clear IOL group , 38 eyes . There were no significant differences between the 3 IOLs in UDVA , CDVA , contrast sensitivity , or question naire responses . The photochromic group had significantly better color vision than the yellow IOL group at 30 lux and better contrast vision at 5 % contrast ( P < .05 ) ; however , there were no significant differences between the photochromic IOL group and the clear IOL group ( P > .05 ) . CONCLUSION : The photochromic blue light – filtering IOL performed as well as the yellow and clear IOLs under photopic conditions . Under mesopic conditions , the yellow IOL gave poor color vision and contrast sensitivity . Financial Disclosure : No author has a financial or proprietary interest in any material or method mentioned PURPOSE : To evaluate contrast sensitivity and glare disability after implantation of an AcrySof IQ Natural SN60WF aspherical intraocular lens ( IOL ) ( Alcon Laboratories ) . SETTING : Iladevi Cataract & IOL Research Centre , Ahmedabad , India . METHODS : One hundred twenty consecutive patients who had phacoemulsification in a prospect i ve triple‐masked trial were r and omized to receive an AcrySof SA60AT IOL ( 40 eyes ) , AcrySof Natural SN60AT IOL ( 40 eyes ) , or AcrySof IQ SN60WF IOL ( 40 eyes ) . At 3 months , contrast sensitivity was measured using the CSV‐1000E contrast sensitivity chart test face ( Vector Vision ) at 3 , 6 , 12 , and 18 cycles per degrees ( cpd ) under photopic conditions ( 85 cd/m2 ) and mesopic conditions ( 2.7 cd/m2 ) with 4.0 mm and 6.0 mm fixed central apertures , with and without glare . The Kruskal‐Wallis test was used and a pair‐wise comparison performed . The main outcome measure was the difference in contrast sensitivity between IOLs at each spatial frequency . RESULTS : The best corrected visual acuity was similar between the 3 IOL groups ( P = .6 ) . The AcrySof IQ group had significantly higher contrast sensitivity at 18 cpd under photopic conditions ( P = .008 ) ; at 3 , 6 , 12 , and 18 cpd during mesopic testing with a 4.0 mm aperture without glare ( P = .018 , P = .011 , P = .007 , and P = .0001 , respectively ) and with glare ( P = .003 , P = .006 , P = .005 , and P = .004 , respectively ) ; and at all spatial frequencies during mesopic testing with a 6.0 mm aperture without glare ( P = .018 , P = .006 , P = .009 , and P = .0001 , respectively ) and with glare ( P = .019 , P = .002 , P = .01 , and P = .017 , respectively ) . CONCLUSION : Eyes with the AcrySof IQ SN60WF IOL had significantly higher contrast sensitivity than eyes with an AcrySof SA60AT or AcrySof Natural SN60AT IOL at all spatial frequencies during mesopic testing ( with and without glare ) with 4.0 and 6.0 mm artificial pupil PURPOSE To compare the quality of vision with aspheric and spherical intraocular lenses ( IOLs ) in pseudophakic patients after long-term follow-up . METHODS Two hundred eyes of 100 patients with bilateral cataracts were r and omly assigned to receive spherical ( Acrysof SN60AT [ Alcon Laboratories Inc ] or Sensar AR40e [ Advanced Medical Optics Inc ] ) or aspheric IOLs ( Acrysof SN60WF [ Alcon ] or Tecnis Z9000 [ Advanced Medical Optics ] ) . Ophthalmologic examination , including best spectacle-corrected visual acuity ( BSCVA ) , pupil size , ocular dominance , contrast sensitivity under mesopic and photopic conditions , and wavefront analysis , was performed 2 months and 1 and 2 years after surgery . RESULTS No statistically significant differences among the four groups in terms of age , pupil diameter , postoperative BSCVA , comeal spherical aberration , and posterior capsular opacification were noted . At all followup examinations , contrast sensitivity results showed no significant differences between the two aspheric IOLs at all spatial frequencies . Under photopic conditions , significant differences ( P<.05 ) between spherical and aspheric IOLs were detected for spatial frequencies of 12 and 18 cycles per degree ( cpd ) at 2 months and 2 years and 12 cpd at 1 year . Under mesopic conditions , significant differences ( P<.05 ) were detected between spherical and aspheric IOLs for all spatial frequencies at 2 months ; all spatial frequencies except 18 cpd at 1 year ; and spatial frequencies of 3 , 12 , and 18 cpd at 2 years . In addition , aspheric IOLs had statistical reductions in total spherical aberration at all follow-up examinations ( P<.01 ) . CONCLUSIONS This study confirms that implantation of a modified aspheric IOL improves functional visual performance at 2 years postoperative Blue light can damage retina and cause age related macular degeneration . After cataract surgery and lens removal retina stays unprotected . Blue light filtering intraocular lenses ( IOL ) increase protection of the retina . In our prospect i ve study we investigated clinical results after bilateral implantation of Acrysof Natural IOL to 30 patients ( N = 60 eyes ) . In a control group ( N = 60 eyes , 30 patients ) , st and ard acrysof IOL was implanted bilaterally . Uncorrected visual acuity ( UCVA ) , best corrected visual acuity ( BCVA ) and Nd YAG laser capsulotomy rate were measured and compared with control group . Subjective patient 's satisfaction and subjective colour perception were also investigated . There was no significant difference in UCVA , BCVA and Nd YAG laser capsulotomy rate between the two groups . High patient 's satisfaction was noticed ( 96.7 % of patients would implant Acrysof Natural IOL again ) . Acrysof Natural IOL enables good visual acuity VA , low rate of Nd YAG laser capsulotomy and high patient 's satisfaction without colour perception disturbances PURPOSE To compare the quality of vision with aspheric and spherical intraocular lenses ( IOLs ) in pseudophakic patients . METHODS This prospect i ve , comparative , r and omized study included 250 eyes of 125 patients with bilateral cataracts . Patients were r and omly assigned to receive either IOLs with a spherical biconvex optic ( Acrysof SN6OAT [ Alcon ] or Sensar AR40e [ Advanced Medical Optics , AMO ] ) or IOLs with an aspheric optic ( Acrysof IQ SN6OWF [ Alcon ] , Tecnis Z9000 [ AMO ] , or Sofport L161AO [ Bausch & Lomb ] ) . Ophthalmologic examination including best spectacle-corrected visual acuity , pupil size , ocular dominance investigation , contrast sensitivity under mesopic and photopic conditions , and wavefront analysis was performed 2 months postoperatively . RESULTS Aspheric IOLs showed better contrast sensitivity compared to spherical IOLs at spatial frequencies of 6 , 12 , and 18 cycles per degree ( cpd ) under photopic conditions and at all spatial frequencies under mesopic conditions . There was no significant difference among the three aspheric IOLs at all spatial frequencies under either photopic or mesopic conditions . Mean total spherical aberration was statistically lower in dominant eyes with aspheric IOLs ( 0.05 + /- 0.06 , 0.11 + /- 0.1 , and 0.19 + /- 0.08 pm for the Tecnis Z9000 , Acrysof IQ SN6OWF , and Sofport L161AO , respectively ) compared with eyes with spherical IOLs ( 0.62 + /- 0.24 and 0.46 + /- 0.19 microm for the Acrysof SN6OAT and Sensar AR40e , respectively ) for a 5-mm pupil diameter . CONCLUSIONS The aspheric IOLs had less wavefront aberrations and performed better under both photopic and mesopic contrast sensitivity compared to the spherical IOLs . These findings confirm it is possible to improve the optical performance of IOLs by modifying the surfaces PURPOSE : To examine color perception in patients receiving bilateral implantation of an ultraviolet ( UV ) and blue‐light filtering intraocular lens ( IOL ) ( AcrySof Natural SN60AT , Alcon Laboratories Inc. ) or a UV‐only filtering IOL ( AcrySof SA60AT ) and to compare the results with those in a phakic group . SETTING : Cincinnati , Ohio , USA . METHODS : In this prospect i ve study , age‐matched subjects who passed the Ishihara test and had visual acuities of 20/25 or better were recruited . There were 2 pseudophakic groups ( bilateral SN60AT or SA60AT IOLs ) and 1 phakic group . The Farnsworth‐Munsell ( FM ) 100‐hue test was administered to each subject twice under different conditions . The phakic and AcrySof Natural SN60AT groups were tested under photopic and mesopic conditions . The SA60AT subjects were further divided into subgroups ( with and without yellow clip‐on lenses ) and tested under photopic and mesopic conditions . RESULTS : A 1‐way analysis of variance ( ANOVA ) of the square‐root‐transformed total error score showed no statistical differences ( P = .637 ) between the treatment groups . Similarly , a 1‐way ANOVA of the red – green error score ( P = .729 ) and blue – yellow error score ( P = .484 ) indicated no statistically significant differences between the treatment groups . The ANOVA results of the FM 100‐hue test under mesopic conditions showed that the total error score in the AcrySof Natural IOL group was significantly lower ( P = .046 ) than in the phakic group . There were no between‐group differences in error scores under mesopic conditions . CONCLUSION : The FM 100‐hue testing showed no difference in color perception between subjects with AcrySof Natural IOLs and those in an age‐matched phakic control group or in those with a UV‐only filtering AcrySof IOL with or without yellow clip‐on lenses PURPOSE : To verify the safety and effectiveness of the new AcrySof Natural ( Alcon Laboratories , Inc. ) blue‐light filtering intraocular lens ( IOL ) , which was design ed to achieve a light‐transmission spectrum similar to that of the natural human crystalline lens . SETTING : Multicenter U.S. clinical trial . METHODS : In a prospect i ve r and omized patient‐masked multicenter study , 150 patients received the AcrySof Natural IOL and 147 patients received the AcrySof single‐piece IOL as a control . Patients with bilateral age‐related cataracts who were willing and able to wait at least 30 days between cataract procedures and had verified normal preoperative color vision were eligible for the study . St and ardized surgery included a 4.0 to 5.0 mm capsulorhexis and phacoemulsification . All lenses were inserted in the capsular bag , with verification of in‐the‐bag placement of both haptics . In all bilateral implantation cases , the same model IOL was used in each eye . Postoperatively , contrast sensitivity and color perception were measured up to 180 days and up to 1 year ( for visual acuity ) after implantation . RESULTS : No statistically significant differences were discovered between the 2 patient groups in visual acuity , contrast sensitivity evaluated under mesopic and photopic conditions , or the number of patients who passed the Farnsworth D‐15 color perception test . There were no lens‐related adverse events in either group . CONCLUSIONS : The blue‐light filtering AcrySof Natural IOL was equivalent to the conventional AcrySof lens in terms of postoperative visual performance . Additional long‐term clinical studies should show whether the IOL actually provides the theoretical benefits to retinal health PURPOSE To compare distance-corrected , near , and intermediate visual acuities as a measurement of depth of focus and spherical aberration of eyes implanted with aspheric and spherical intraocular lenses ( IOLs ) . DESIGN R and omized prospect i ve study . PARTICIPANTS One hundred twenty eyes of 60 patients with bilateral cataract implanted with 3 IOL models ( AcrySof IQ , AcrySof SN60AT [ Alcon Laboratories , Fort Worth , TX ] , and Sensar AR40 [ Allergan Surgical , Irvine , CA ] ) . METHODS Pupil diameter was analyzed by using a Colvard pupillometer ( OASIS Medical , Inc. , Glendora , CA ) under photopic , mesopic , and scotopic conditions . Distance ( 6 m ) , intermediate ( 1 m ) , and near ( 0.33 m ) visual acuities were measured with distance correction in place 90 days after surgery . Wavefront analysis ( LadarWave ; Alcon Laboratories ) was performed using 5-mm and measured photopic pupil diameter at 30 and 90 days after surgery . MAIN OUTCOME MEASURES To evaluate spherical aberration and depth of focus ( by means of distance-corrected near and intermediate visual acuity ) in patients implanted with aspheric and spherical IOLs . RESULTS Photopic pupil sizes in each group were similar at 30 days after surgery . At 90 days after surgery , mean logarithm of the minimum angle of resolution distance-corrected near visual acuity ( + /-st and ard deviation [ SD ] ) was 0.50+/-0.20 in the AcrySof IQ group , 0.38+/-0.17 in the AcrySof SN60AT group , and 0.45+/-0.16 in Sensar AR40 group . Mean spherical aberration values ( + /-SD ) were 0.03+/-0.05 microm in the AcrySof IQ group , 0.24+/-0.04 microm in the AcrySof SN60AT group , and 0.14+/-0.07 microm in the Sensar AR40 group . The AcrySof IQ group showed a statistically significant lower induction of spherical aberration and worse distance-corrected near visual acuity . The AcrySof SN60AT group showed statistically significant higher mean spherical aberration values and better distance-corrected near and intermediate visual acuity . CONCLUSIONS The reduction of total spherical aberration after aspheric IOL implantation may de grade distance-corrected near and intermediate visual acuity |
11,104 | 15,690,209 | The current literature does not provide a reliable answer to whether operative or conservative treatment is more effective for unstable traumatic thoracolumbar fractures . | The management of unstable traumatic thoracolumbar fractures without neurological deficits remains controversial .
The objective of this study was to compare the effectiveness of operative and conservative treatment of unstable traumatic thoracolumbar fractures . | STUDY DESIGN A retrospective review of 42 patients treated at three major medical centers for burst fractures of L3 , L4 , and L5 . This is the largest low lumbar ( L3-L5 ) burst fracture study in the literature to date . The study was design ed to assess both radiographic and clinical outcomes in a cohort of patients treated during a 16-year period . OBJECTIVES The objective of this study was to determine whether conservatively treated patients with low lumbar burst fractures had satisfactory outcomes compared with those in a surgically treated cohort of patients . The study included patients with and without neurologic deficits . SUMMARY OF BACKGROUND DATA Burst fractures of the low lumbar spine ( L3-L5 ) represent a small percentage of all spine fractures . The iliolumbar ligaments and location below the pelvic brim are two stabilizing factors that are unique to these fractures when compared with burst fractures at the thoracolumbar junction . METHODS Forty-two ( n = 42 ) patients with low lumbar burst fractures were identified from 1980 through 1996 . Medical records , radiographs , and follow-up Dallas Pain Question naires were obtained . Loss of anterior vertebral height , kyphotic angulation , and amount of retropulsion were recorded at several phases of treatment . Mean follow-up time was 45.2 months ( range , 5 - 132 months ) . Twenty patients were treated without surgery ( 18 were neurologically intact , and 2 had isolated nerve root injury ) , and 22 underwent surgery ( 14 had neurologic injury , 8 were intact ) . RESULTS No patient showed neurologic deterioration , regardless of treatment . Fracture of the third lumbar segment showed the greatest tendency toward kyphotic collapse and loss of height in the nonoperative group , although this was not reflected in the final functional outcome of both groups . The ability to return to work and achieve a good-to-excellent long-term result was not significantly different among fracture levels or between surgical and nonsurgical treatments . CONCLUSIONS The results of nonoperative treatment of low lumbar burst fractures were comparable with those of operative treatment . The rate of repeat surgery ( 41 % ) and absence of a clearly definable long-term functional or radiographic benefit in patients without neurologic compromise may make surgery less appealing Study Design . Prospect i ve cohort study . Objectives . To study the predictive value of magnetic resonance imaging ( MRI ) findings of thoracolumbar spine fractures concerning the radiologic and clinical outcome . Summary of Background Data . Disagreement about the proper treatment of thoracolumbar spine fractures is caused by insufficiency of conventional imaging techniques . Previous studies have shown that MRI is capable of distinguishing injury to all structures of the fractured spine and thus may help develop schemes with higher predictive power . Methods . A total of 53 patients with 71 fractures were studied with MRI in a prospect i ve fashion . A total of 24 patients with 39 fractures were treated conservatively and 29 patients with 32 fractures were treated operatively after a protocol concerning the treatment options . MRI scans were obtained within 1 week of injury and at the 2-year follow-up . Pain scores were obtained at the 2-year follow-up . Previously described MRI schemes concerning the trauma and post-trauma conditions were used . Results and Conclusions . An unfavorable outcome in the conservative group was related to the progression of kyphosis , which in most cases was predictable with the use of trauma MRI findings concerning the endplate comminution and vertebral body involvement . In the operatively treated group , recurrence of the kyphotic deformity was predictable by the lesion of the posterior longitudinal ligamentary complex together with endplate comminution and vertebral body involvement as seen on trauma MRI . The authors recommend the use of MRI to develop reliable prognostic criteria for these injuries BACKGROUND Both surgery and recumbency have been adopted in the treatment of spinal fractures . Herein we present the indications for each , and our experience with thoracolumbar junction ( T12 , L1 and L2 ) burst fractures . METHODS Sixty-eight patients with thoracolumbar burst fractures were treated operatively in 36 cases , and nonoperatively in 32 with recumbency for 1 - 6 weeks . Treatment was based on clinical and radiological criteria . Eighty-one percent of the recumbency patients , but only 14 % of the surgical patients were intact on admission . Patients were followed for a mean+/-SD of 9+/-10 months in the recumbency group , and 21+/-21 months in the surgical group . RESULTS Neurological improvement and progressive angular deformity occurred in both groups . The cost of recumbency in our patients was nearly half that of those who required surgery , though the length of hospitalization between the two groups was similar at 1 month + /-2 weeks . CONCLUSION The above study emphasizes that the selection of operative versus nonoperative treatment in burst fractures should not be r and om but based on clinical as well as radiological criteria . Recumbency is favored in patients who are intact , with angular deformity less than 20 degrees , a residual spinal canal greater than 50 % of normal , and an anterior body height exceeding 50 % of the posterior height . Surgical intervention is generally indicated in patients with partial neurological deficit , and those with severe instability Study Design . A prospect i ve clinical trial was conducted . Objective . To compare the results of nonoperative treatment versus short-segment posterior fixation using pedicle screws . Summary of Background Data . A previous study showed that nonoperative treatment with early mobilization produced good results , even when the posterior column was involved . Methods . This study involved 80 patients . Inclusion criteria required the following : neurologically intact patient , single-level closed burst fracture involving T11–L2 , no fracture dislocations or pedicle fractures , age of 18 to 65 years ( nonpathologic adult ) , and no other major organ system or musculoskeletal injuries . Patients in the nonoperative group ( n = 47 ) were allowed activity to the point of pain tolerance beginning on the day of injury using a hyperextension brace . Patients in the operative group ( n = 33 ) underwent three-level , ( one above , one at fracture level , and one below ) fixation using VSP or TSRH instrumentation . The follow-up period was 2 years . Results . The surgical group had less pain up to 3 months and a better Greenough Low Back Outcome Score up to 6 months , but the outcome was similar afterward . No neurologic deficit in any patient . In the nonoperative group , the kyphosis angle worsened by 4 ° , and the retropulsion decreased from 34 % to 15 % . In the operative group , there was one case of superficial infection and two cases of broken screws . The kyphosis angle was improved initially by 17 ° , but this was gradually lost . Hospital charges were four times higher in the operative group . Conclusions . Short-segment posterior fixation provides partial kyphosis correction and earlier pain relief , but the functional outcome at 2 years is similar . Early activity to the point of pain tolerance can be safely allowed This study consisted of 1,019 spinal fracture patients followed prospect ively for 2 years . Sixty-four physicians from 12 countries participated . The purpose of the study was to determine : 1 ) the relationship between neurologic deficit and fracture type , level , and spinal canal compromise ; 2 ) the neurologic outcome comparing surgical versus nonsurgical treatment and anterior versus posterior surgery ; and 3 ) the relationship of pain to both kyphotic deformity and to surgical and nonsurgical treatment . The main findings of this study are as follows : 1 ) seat belts reduced the incidence of severe neurologic injury ; 2 ) there was a higher incidence of neurologic deficit with fracture-dislocations and a higher incidence of neurologically intact patients with compression and flexion-distraction injuries ; 3 ) there was a greater incidence of complete neurologic deficits caused by fractures at the spinal cord level , and a diminished incidence at the cauda equina level ; 4 ) for burst fractures there was a weakly positive relationship between canal compromise and neurologic deficit , including bladder function ; 5 ) surgical intervention led to a greater percentage of improved neurologic function than nonoperative treatment , but the rate of improvement was not statistically different ; 6 ) anterior surgery was not more effective than posterior surgery in improving the neurologic function when function was assessed using the Frankel or Motor Index scales , but it was statistically significant when compared to the Manabe scale ; 7 ) in patients who deteriorated before surgery and underwent surgery , there was a greater improvement neurologically , particularly for anterior surgery , compared to those patients treated nonoperatively or to the overall surgically treated group ; 8) There was a statistically significant relationship between bladder function and fracture type , with an increased incidence of absent function seen with fracture-dislocations , of impaired function with burst fractures , and of intact bladder function with compression and flexion-distraction injuries ; 9 ) anterior surgery was more beneficial in improving complete bladder impairment to partial impairment compared to posterior surgery ; 10 ) a kyphotic deformity of greater than 30 degrees at 2-year follow-up was associated with an increased incidence of significant back pain ; 11 ) patients who had surgery complained less of severe pain than those who were treated without surgery |
11,105 | 12,020,146 | and Over the past 2 weeks , have you felt little interest or pleasure in doing things ? ) ,
appear to perform as well as longer instruments . | Depressive disorders are common , chronic , and costly .
Prevalence rates from community-based surveys range from 1.8 % to 3.3 % for depression within the past month and 4.9 % to 17.1 % for lifetime prevalence ( 1 , 2 ) .
In primary care setting s , the point prevalence of major depression ranges from 4.8 % to 8.6 % ( 3 ) .
Depressive illness is projected to be the second leading cause of disability worldwide in 2020 ( 4 ) .
The substantial public health and economic significance of depression is reflected by its considerable effect on health care utilization and great monetary costs : $ 43 billion annually , of which $ 17 billion represents lost work days ( 5 , 6 ) .
Despite the high prevalence and substantial impact of depression , detection and treatment in the primary care setting have been suboptimal .
Studies have shown that usual care by primary care physicians fails to recognize 30 % to 50 % of depressed patients ( 7 ) .
Because patients in whom depression goes unrecognized can not be appropriately treated , systematic screening has been advocated as a means of improving detection , treatment , and outcomes of depression .
In 1996 , the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for depression with st and ardized question naires ( 8) .
Specifically , we examined three key questions : 1 ) What is the accuracy of case-finding instruments for depression in primary care population s ?
2 ) Is treatment of depression in primary care patients effective in improving outcomes ?
3 ) Is routine systematic identification with case-finding questions ( screening ) , with or without integrated management and follow-up systems , more effective than usual care in identifying patients with depression , facilitating treatment of patients with depression , and improving clinical outcomes ?
Brief instruments , including asking the patient two questions about the presence of depressed mood and anhedonia ( Over the past 2 weeks , have you felt down , depressed or hopeless ?
Effective treatments , including pharmacologic and behavioral or counseling interventions , are available for depressed patients identified in primary care setting s ( 9 ) .
Characteristics of Case-Finding Instruments Used To Detect Depression in Adults in Primary Care Setting s We also examined the evidence on whether screening for depression in primary care setting s affects recognition , treatment , and clinical outcomes of adult patients with depression .
In this article , we review the evidence pertaining to this overarching question . | CONTEXT Significant symptoms of depression are common in the older community-dwelling population . Although depressive symptoms and disability may commonly occur in the same person , whether depressive symptoms contribute to subsequent functional decline has not been eluci date d. OBJECTIVE To determine whether depressive symptoms in older persons increase the risk of subsequent decline in physical function as measured by objective performance-based tests . DESIGN A 4-year prospect i ve cohort study . SETTING The communities of Iowa and Washington counties , Iowa . PARTICIPANTS A total of 1286 persons aged 71 years and older who completed a short battery of physical performance tests in 1988 and again 4 years later . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale . Physical performance tests included an assessment of st and ing balance , a timed 2.4-m ( 8-ft ) walk , and a timed test of 5 repetitions of rising from a chair and sitting down . RESULTS After adjustment for baseline performance score , health status , and sociodemographic factors , increasing levels of depressive symptoms were predictive of greater decline in physical performance over 4 years ( odds ratio for decline in those with depressed mood vs those without , 1.55 ; 95 % confidence interval [ CI ] , 1.02 - 2.34 ) . Even among those at the high end of the functional spectrum , who reported no disability , the severity of depressive symptoms predicted subsequent decline in physical performance ( odds ratio for decline , 1.03 ; 95 % CI , 1.00 - 1.08 ) . CONCLUSIONS This study provides evidence that older persons who report depressive symptoms are at higher risk of subsequent physical decline . These results suggest that prevention or reduction of depressed mood could play a role in reducing functional decline in older persons BACKGROUND Exp and ing access to high- quality depression treatment will depend on the balance of incremental benefits and costs . We examine the incremental cost-effectiveness of an organized depression management program for high utilizers of medical care . METHODS Computerized records at 3 health maintenance organizations were used to identify adult patients with outpatient medical visit rates above the 85th percentile for 2 consecutive years . A 2-step screening process identified patients with current depressive disorders , who were not in active treatment . Eligible patients were r and omly assigned to continued usual care ( n = 189 ) or to an organized depression management program ( n = 218 ) . The program included patient education , antidepressant pharmacotherapy initiated in primary care ( when appropriate ) , systematic telephone monitoring of adherence and outcomes , and psychiatric consultation as needed . Clinical outcomes ( assessed using the Hamilton Depression Rating Scale on 4 occasions throughout 12 months ) were converted to measures of " depression-free days . " Health services utilization and costs were estimated using health plan-st and ardized cl aims . RESULTS The intervention program led to an adjusted increase of 47.7 depression-free days throughout 12 months ( 95 % confidence interval [ CI ] , 28.2 - 67.8 days ) . Estimated cost increases were $ 1008 per year ( 95 % CI , $ 534-$1383 ) for outpatient health services , $ 1974 per year for total health services costs ( 95 % CI , $ 848-$3171 ) , and $ 2475 for health services plus time-in-treatment costs ( 95 % CI , $ 880-$4138 ) . Including total health services and time-in-treatment costs , estimated incremental cost per depression-free day was $ 51.84 ( 95 % CI , $ 17.37-$108.47 ) . CONCLUSIONS Among high utilizers of medical care , systematic identification and treatment of depression produce significant and sustained improvements in clinical outcomes as well as significant increases in health services costs OBJECTIVE A r and omized controlled trial was conducted to examine the clinical effectiveness of providing general practitioners ( GPs ) with the results of a self-administered computerized assessment of common mental disorders . METHOD Attenders at a general practice in a deprived inner city area of South London were identified using case finding question naires . Six hundred and eighty-one subjects were r and omly allocated to three groups which differed in the information provided to the GP : 1 ) no additional information was given to the GP ; 2 ) the results of the 12 item General Health Question naire ( GHQ ) were given to the GP ( the GHQ is a paper and pencil question naire that assesses common mental disorders ) ; 3 ) the results of a self-administered computerized assessment ( PROQSY ) of common mental disorders were provided for the GP . RESULTS Clinical outcome was assessed using the 12-item GHQ . Consultations with the GP , prescriptions and referrals within and outside the practice were also recorded . The group in whom the GP received the results of the computerized assessment showed a modest clinical improvement , relative to the other two groups after 6 weeks . There was no difference in clinical outcome between the groups at 6 months . There appeared to be no increase in consultations or prescriptions in the computerized assessment group . CONCLUSIONS Self-administered computerized assessment s for psychiatric disorder have potential as a means of improving the clinical outcome of patients in primary care . It is likely that the effectiveness of the approach would be greatly increased by linking the results of computerized assessment s to clinical practice guidelines , tailored to the individual patient by means of computerized technology The usefulness of the Zung Self-Rating Depression Scale as a screening instrument to uncover masked depression , and the benefits of early identification and treatment with alprazolam , were evaluated in a general medical practice population . There was a 95 % scale acceptance by patients and a 12 % overall prevalence of depression based on SDS results . Patients who scored in the depressed range on the SDS were , on a r and omized basis , either identified immediately to their physicians and treated with alprazolam ( N = 21 ) or identified after 4 weeks ( natural history controls , N = 20 ) . Treatment result ed in improvement in 66 % of the identified group versus a 35 % spontaneous improvement in the control group ( p less than .05 ) OBJECTIVE To evaluate the recognition , management , and outcomes of depressed patients presenting in primary care . DESIGN Epidemiologic survey with 12-month follow-up . SETTING Primary care clinics of a staff-model health maintenance organization . PATIENTS AND MAIN OUTCOME MEASURES Consecutive primary care attenders aged 18 to 65 years ( n = 1952 ) were screened using the 12-item General Health Question naire ( GHQ-12 ) , and a stratified r and om sample ( n = 373 ) completed a psychiatric assessment , including the Composite International Diagnostic Interview ( CIDI ) , the 28-item GHQ , and a brief self-rated disability question naire ( BDQ ) . Three-month follow-up assessment ( n = 347 ) repeated the GHQ-28 and BDQ , and 12-month follow-up ( n = 308 ) repeated the CIDI , GHQ-28 , and BDQ . Use of psychotropic drugs and mental health services was assessed using computerized pharmacy and visit registration records . RESULTS Structured interviews found 64 cases of current major depression ( weighted prevalence , 6.6 % ) and 58 cases of current subthreshold depression ( weighted prevalence , 8.8 % ) . Of those with major depression , 64 % ( n = 41 ) were recognized as psychologically distressed by the primary care physician , 56 % ( n = 36 ) filled at least one antidepressant prescription during the next 3 months , and 39 % ( n = 25 ) made at least one specialty mental health visit . Compared with recognized cases , those with unrecognized major depression were less symptomatic at baseline ( GHQ-28 score , 15.31 vs 11.07 ; P = .006 ) but showed a similar rate of improvement over 12 months ( F test for difference in slopes , P = .93 ) . CONCLUSIONS While many depressed primary care patients may go unrecognized and untreated , this group appears to have milder and more self-limited depression . A narrow focus on increased recognition may not improve overall outcomes . Treatment re sources might be best directed toward more intensive follow-up and relapse prevention among those now treated Depressive disorders are common , persistent , and recurring afflictions among primary care patients . They cause substantial suffering for patients and their families and are associated with a loss of personal productivity and a markedly increased risk for suicide . Further , the presence of depression puts persons with comorbid conditions , such as recent myocardial infa rct ion , at increased risk for illness and death . Persons with depression spend more time with their physicians during office visits and use more health care than persons without depression [ 1 ] . The annual health care cost associated with depression in the United States is estimated to be $ 43.7 billion [ 2 ] . Underscoring the importance of identifying patients with depression is that the effectiveness of therapy , including antidepressants , psychotherapy , and counseling , has clearly been established [ 3 ] . Despite these issues , primary care providers fail to diagnose and treat as many as 35 % to 50 % of patients with depressive disorders [ 4 , 5 ] . Obstacles to the appropriate recognition of depression include inadequate provider knowledge of diagnostic criteria ; competing comorbid conditions and priorities among primary care patients ; time limitations in busy office setting s ; concern about the implication s of labeling ; poor reimbursement mechanisms ; and uncertainty about the value , accuracy , and efficiency of screening mechanisms for identifying patients with depression . We address the last of these obstacles and assess the feasibility and operating characteristics of several case-finding instruments that have been used to detect depressive disorders in primary care setting s. Our ultimate goal is to familiarize providers with the advantages and disadvantages of these instruments so that they can make informed decisions about incorporating them into practice . Methods Data Acquisition We did a MEDLINE search of the English- language medical literature published from 1966 through February 1994 . Search terms included depressive disorder or depression , diagnosis , and the specific names of each of 11 case-finding instruments cited in previous relevant review s or bibliographies [ 6 - 9 ] . Other sources were references identified from pertinent articles and national experts in the field of depression . Experts included authors of papers that were selected for review and two members of the Agency for Health Care Policy and Research Guideline Panel on Depression . Of 906 articles identified through MEDLINE , 210 were deemed potentially relevant . These were review ed to identify studies that met the following selection criteria . Study sample s had to have been composed of primary care patients attending clinic . Patients were excluded if they had been selected because they had specific conditions ( such as chronic pain or cancer ) or because they had specific demographic characteristics ( for example , they were immigrants in a particular ethnic group ) . Both a case-finding instrument and a diagnostic criterion st and ard had to have been administered . The criterion st and ard had to have had formal st and ardized diagnostic criteria for depression . Accepted criterion st and ards were the Diagnostic Schedule Manual-3 criteria ( DSM-III or DSM-III-R ) and the Research Diagnostic Criteria , or a close approximation of these . St and ard interview procedures , such as the Diagnostic Interview Schedule or the Structured Clinical Interview for DSM-III , had to have been used to arrive at the diagnosis . Chart or physician diagnoses of depression that were made without specified formal interview procedures and diagnostic criteria were excluded . Nineteen studies involving nine case-finding instruments met the selection criteria : Fourteen were found during the MEDLINE search ; 1 came from a relevant bibliography ; and 4 were unpublished at the time of the search and came from experts [ 10 - 28 ] . Of the remaining articles screened , 92 % were excluded because they did not involve primary care patients , 6 % were excluded because they had used an inadequate criterion st and ard , and 2 % were excluded because they involved selected population s [ 29 , 30 ] or because they had tested modified and unvali date d versions of case-finding instruments [ 31 ] . Data Extraction Articles were abstract ed by two independent review ers . Determination of study quality was made on the basis of 1 ) whether the case-finding instrument was administered and interpreted independently of the criterion st and ard and 2 ) whether the proportion of persons receiving the criterion st and ard assessment was less than or more than 50 % of those approached for criterion st and ard assessment . Quality assessment addressed method ologic issues relevant to the evaluation of diagnostic tests ( such as independent assessment and selection bias ) and did not necessarily reflect the ability of studies to address their original aims . There were no disagreements about quality assessment s. Data Synthesis Established cut-points for case-finding instruments ( Table 1 ) were used . Two-by-two tables were constructed that categorized numbers of screened-positive and screened-negative persons who did and did not meet criterion st and ard diagnosis for major depression and major depression or dysthymia . Kraemer 's method [ 32 ] was used to adjust for verification bias for studies that used two-stage assessment techniques ; whereby the criterion st and ard was administered only to a r and om sample of persons who screened negative on case-finding instruments [ 33 ] . The authors of all but one study provided us with additional data and analyses when two-by-two tables could not be derived from abstract ion of the published article . This one study [ 28 ] was dropped from further review because its authors could not be contacted and tables could not be derived from published information . Table 1 . Characteristics of Case-Finding Instruments That Have Been Used to Detect Depression in Primary Care Setting s * A scattergram ( Figure 1 ) plotting true-positive against false-positive rates was constructed to visually evaluate variability among studies [ 34 ] . To provide a visual reference for the consistency of study results , we modeled a summary receiver-operating curve based on the logit transformations of the true-positive and false-positive rates . Figure 1 . Plot of true-positive rate against false-positive rate for case-finding instruments to detect major depression . Average sensitivities and specificities , weighted by study size and corrected for two-stage assessment techniques when indicated , were computed both by case-finding instrument and by overall instruments [ 35 ] . The point estimates and 95 % CIs were calculated using a linear r and om-effects model [ 36 , 37 ] . Approximate 95 % CIs were estimated using quadratic root formulae because most of the point estimates were near unity [ 37 ] . Differences in weighted average sensitivities and specificities between case-finding instruments were evaluated using the z statistic with the Scheffe multiple-comparison adjustment [ 37 ] . Stratified analyses were done to evaluate whether estimated sensitivities and specificities varied between high- quality studies and those with major selection bias or lack of independent assessment . Regression analysis was used to determine associations between reported study prevalences and sensitivity estimates [ 37 ] . Results Descriptions of Case-Finding Instruments Characteristics of the nine case-finding instruments that have been evaluated in primary care setting s are presented in Table 1 . All of the question naires are written either at the easy ( 3rd to 5th grade ) or average ( 6th to 9th grade ) reading level [ 38 ] . Almost all can be self-administered in less than 5 minutes . Except for the General Health Question naire , all include specific questions aim ed at assessing depressed mood or whether a patient feels sad or blue . All include questions assessing anhedonia . Most are available in language s other than English , such as Spanish . The Beck Depression Inventory , the Center for Epidemiologic Studies Depression Screen , and the Zung Self- Assessment Depression Scale are three commonly used , traditional instruments that were developed specifically to identify depression . They include similar numbers of questions and use response formats that rely either on ranking symptom severity or on classifying frequency of symptoms . The time frames of questions are today for the Beck Depression Inventory , over the past week for the Center for Epidemiologic Studies Depression Screen , and recently for the Zung Self- Assessment Depression Scale . These three instruments have been used in numerous setting s ( including the community , the clinic , and the hospital ) not only to identify depression but also to rate severity of depression and to monitor response to therapy . The General Health Question naire and the Hopkins Symptom Checklist are question naires that screen for general psychiatric illness ; the Hopkins Checklist has a specific category for depression . Both of these instruments have several versions with different numbers of questions . The Medical Outcomes Study Depression Screen is a depression-specific screening instrument that was developed by combining two questions from the Diagnostic Interview Schedule [ 39 ] with six questions from the Center for Epidemiologic Studies Depression Screen . A logistic regression scoring method is used ; this requires a calculator . The Primary Care Evaluation of Mental Disorders ( PRIME-MD ) and the Symptom Driven Diagnostic System- Primary Care instruments are recently developed , multidimensional question naires . Each has screening questions arranged in several categories ( for example , mood or depression , anxiety , alcohol abuse , and somatization ) that are used to trigger more extensive diagnostic interviewing sections for specific DSM-III-R diagnoses . The depression components of these two instruments include the fewest questions of all case-finding instruments that have been studied in primary care setting s. Descriptions of Studies and CONTEXT Depression is a leading cause of disability worldwide , but treatment rates in primary care are low . OBJECTIVE To determine the cost-effectiveness from a societal perspective of 2 quality improvement ( QI ) interventions to improve treatment of depression in primary care and their effects on patient employment . DESIGN Group-level r and omized controlled trial conducted June 1996 to July 1999 . SETTING Forty-six primary care clinics in 6 community-based managed care organizations . PARTICIPANTS One hundred eighty-one primary care clinicians and 1356 patients with positive screening results for current depression . INTERVENTIONS Matched practice s were r and omly assigned to provide usual care ( n = 443 patients ) or to 1 of 2 QI interventions offering training to practice leaders and nurses , enhanced educational and assessment re sources , and either nurses for medication follow-up ( QI-meds ; n = 424 patients ) or trained local psychotherapists ( QI-therapy ; n = 489 ) . Practice s could flexibly implement the interventions , which did not assign type of treatment . MAIN OUTCOME MEASURES Total health care costs , costs per quality -adjusted life-year ( QALY ) , days with depression burden , and employment over 24 months , compared between usual care and the 2 interventions . RESULTS Relative to usual care , average health care costs increased $ 419 ( 11 % ) in QI-meds ( P = .35 ) and $ 485 ( 13 % ) in QI-therapy ( P = .28 ) ; estimated costs per QALY gained were between $ 15 331 and $ 36 467 for QI-meds and $ 9478 and $ 21 478 for QI-therapy ; and patients had 25 ( P = .19 ) and 47 ( P = .01 ) fewer days with depression burden and were employed 17.9 ( P = .07 ) and 20.9 ( P = .03 ) more days during the study period . CONCLUSIONS Societal cost-effectiveness of practice -initiated QI efforts for depression is comparable with that of accepted medical interventions . The intervention effects on employment may be of particular interest to employers and other stakeholders OBJECTIVE : To describe primary care physicians ’ clinical decision making regarding late-life depression . DESIGN : Longitudinal collection of data regarding physicians ’ clinical assessment s and the volume and content of patients ’ ambulatory visits as part of a r and omized clinical trial of a physician-targeted intervention to improve the treatment of late-life depression . SETTING : Academic primary care group practice . PATIENTS / PARTICIPANTS : One-hundred and eleven primary care physicians who completed a structured question naire to describe their clinical assessment s immediately following their evaluations of 222 elderly patients who had reported symptoms of depression on screening question naires . EVTERVENTIONS : Intervention physicians were provided with their patient ’s score on the Hamilton Depression rating scale ( HAM-D ) and patient-specific treatment recommendations prior to completing the question naire regarding their clinical assessment .MAIN RESULTS : Those physicians not provided HAM-D scores were just as likely to rate their patients as depressed , as determined by specific query of these physicians regarding their clinical assessment s. A physician ’s clinical rating of likely depression did not consistently result in the formulation of treatment intentions or actions . Treatment intentions and actions were facilitated by provision of treatment algorithms , but treatment was received by fewer than half of the patients whom physicians intended to treat . Barriers to treatment appear to include both physician and patient doubts about treatment benefits . CONCLUSIONS : Lack of recognition of depressive symptoms did not appear to be the primary barrier to treatment . Recognition of symptoms and access to treatment algorithms did not consistently result in progression to subsequent stages in treatment decision making . More research is needed to determine how patients and physicians weigh the potential risks and benefits of treatment and how accurately they make these judgments Medical records of 150 medical ambulatory care patients r and omly assigned to groups in which screening for depression , physician sensitization about depression , and informational feedback to physicians were systemically varied were review ed for physician notations about depression and its treatment . Forty-two percent of the 100 patients screened with the Zung self-rating depression scale had scores outside the normal range . Chart notation about depression was effectively and appropriately increased by feedback and sensitization from 8 to 25 percent , but these procedures were less effective in increasing treatment interventions , which were noted for 12 percent of the entire sample . Physicians responded to patient information about depression presented to them in the format of a laboratory test , and such previsit screening devices may increase physician attention to psychological problems in general medical setting CONTEXT Care of patients with depression in managed primary care setting s often fails to meet guideline st and ards , but the long-term impact of quality improvement ( QI ) programs for depression care in such setting s is unknown . OBJECTIVE To determine if QI programs in managed care practice s for depressed primary care patients improve quality of care , health outcomes , and employment . DESIGN R and omized controlled trial initiated from June 1996 to March 1997 . SETTING Forty-six primary care clinics in 6 US managed care organizations . PARTICIPANTS Of 27332 consecutively screened patients , 1356 with current depressive symptoms and either 12-month , lifetime , or no depressive disorder were enrolled . INTERVENTIONS Matched clinics were r and omized to usual care ( mailing of practice guidelines ) or to 1 of 2 QI programs that involved institutional commitment to QI , training local experts and nurse specialists to provide clinician and patient education , identification of a pool of potentially depressed patients , and either nurses for medication follow-up or access to trained psychotherapists . MAIN OUTCOME MEASURES Process of care ( use of antidepressant medication , mental health specialty counseling visits , medical visits for mental health problems , any medical visits ) , health outcomes ( probable depression and health-related quality of life [ HRQOL ] ) , and employment at baseline and at 6- and 12-month follow-up . RESULTS Patients in QI ( n = 913 ) and control ( n = 443 ) clinics did not differ significantly at baseline in service use , HRQOL , or employment after nonresponse weighting . At 6 months , 50.9 % of QI patients and 39.7 % of controls had counseling or used antidepressant medication at an appropriate dosage ( P<.001 ) , with a similar pattern at 12 months ( 59.2 % vs 50.1 % ; P = .006 ) . There were no differences in probability of having any medical visit at any point ( each P > or = .21 ) . At 6 months , 47.5 % of QI patients and 36.6 % of controls had a medical visit for mental health problems ( P = .001 ) , and QI patients were more likely to see a mental health specialist at 6 months ( 39.8 % vs 27.2 % ; P<.001 ) and at 12 months ( 29.1 % vs 22.7 % ; P = .03 ) . At 6 months , 39.9 % of QI patients and 49.9 % of controls still met criteria for probable depressive disorder ( P = .001 ) , with a similar pattern at 12 months ( 41.6 % vs 51.2 % ; P = .005 ) . Initially employed QI patients were more likely to be working at 12 months relative to controls ( P = .05 ) . CONCLUSIONS When these managed primary care practice s implemented QI programs that improve opportunities for depression treatment without m and ating it , quality of care , mental health outcomes , and retention of employment of depressed patients improved over a year , while medical visits did not increase overall This study reports the efficacy of the General Health Question naire ( G.H.Q. ) in the secondary prevention of minor psychiatric illness in a primary -care setting . 1093 consecutive attenders at a general practitioner 's surgery were screened for minor psychiatric disorder using the G.H.Q. 32 % were found to have a conspicuous psychiatric disorder and a further 11 % had a hidden psychiatric disorder . The group with hidden disorders were r and omly assigned to a treated index group and an untreated control group . The effects of case detection and treatment were beneficial and immediate , with the duration of episode of the disorder being much shorter for patients whose disorder was recognised by the general practitioner . For patients with more severe disorders there are significant differences still demonstrable between the groups one year later ; but patients with mild disorders do equally well , some recovering spontaneously but others becoming manifest to the general practitioner over the next year and so receiving treatment . The " detected " group of patients increased their consultations for emotional complaints over the next year , but their total consultation-rate was not increased A r and omized clinical trial was performed to assess whether the results of a depression screening instrument , when provided to physicians , could influence their recognition and treatment of depression in a primary care setting . The intervention consisted of r and omly informing or not informing physicians of the depression status of 100 patients who screened positively for depression on both the Zung Self-rating Depression Scale ( SDS ) and a DSM-III screen . For 12 months patients were followed to assess depression status , and medical records were audited to assess depression recognition and treatment . Results show that feedback to physicians of SDS scores of previously unrecognized depressed patients makes a significant difference in greater recognition ( 56.2 % vs. 34.6 % ) and treatment ( 56.2 % vs. 42.3 % ) of depression over the 12-month study period . This was especially true for patients with high somatic ( P < 0.05 ) or low psychologic symptoms of depression ( P < 0.05 ) . These results suggest that routine use of a depression screening instrument can improve physician recognition of depression , with increased initiation of treatment OBJECTIVE : To determine the effect of case-finding for depression on frequency of depression diagnoses , prescriptions for antidepressant medications , prevalence of depression , and health care utilization during 2 years of follow-up in elderly primary care patients . DESIGN : R and omized controlled trial . SETTING : Thirteen primary care medical clinics at the Kaiser Permanente Medical Center , an HMO in Oakl and , Calif , were r and omly assigned to intervention conditions ( 7 clinics ) or control conditions ( 6 clinics ) . PARTICIPANTS : A total of 2,346 patients aged 65 years or older who were attending appointments at these clinics and completed the 15-item Geriatric Depression Scale ( GDS ) . GDS scores of 6 or more were considered suggestive of depression . INTERVENTIONS : Primary care physicians in the intervention clinics were notified of their patients ’ GDS scores . We suggested that participants with severe depressive symptoms ( GDS score ≥ 11 ) be referred to the Psychiatry Department and participants with mild to moderate depressive symptoms ( GDS score of 6–10 ) be evaluated and treated by the primary care physician . Intervention group participants with GDS scores suggestive of depression were also offered a series of organized educational group sessions on coping with depression led by a psychiatric nurse . Primary care physicians in the control clinics were not notified of their patients ’ GDS scores or advised of the availability of the patient education program ( usual care ) . Participants were followed for 2 years . MEASUREMENTS AND MAIN RESULTS : Physician diagnosis of depression , prescriptions for antidepressant medications , prevalence of depression as measured by the GDS at 2-year follow-up , and health care utilization were determined . A total of 331 participants ( 14 % ) had GDS scores suggestive of depression ( GDS ≥ 6 ) at baseline , including 162 in the intervention group and 169 in the control group . During the 2-year follow-up period , 56 ( 35 % ) of the intervention participants and 58 ( 34 % ) of the control participants received a physician diagnosis of depression ( odds ratio [ OR ] , 1.0 ; 95 % confidence interval [ CI ] , 0.6 to 1.6 ; P=.96 ) . Prescriptions for antidepressants were received by 59 ( 36 % ) of the intervention participants and 72 ( 43 % ) of the control participants ( OR , 0.8 ; 95 % CI , 0.5 to 1.2 ; P=.3 ) . Two-year follow-up GDS scores were available for 206 participants ( 69 % of survivors ) : at that time , 41 ( 42 % ) of the 97 intervention participants and 54 ( 50 % ) of the 109 control participants had GDS scores suggestive of depression ( OR , 0.7 ; 95 % CI , 0.4 to 1.3 ; P=.3 ) . Comparing participants in the intervention and control groups , there were no significant differences in mean GDS change scores ( −2.4±SD 3.7 vs −2.1 SD±3.6 ; P=.5 ) at the 2-year follow-up , nor were there significant differences in mean number of clinic visits ( 1.8±SD 3.1 vs 1.6±SD 2.8 ; P=.5 ) or mean number of hospitalizations ( 1.1±SD 1.6 vs 1.0±SD 1.4 ; P=.8 ) during the 2-year period . In participants with initial GDS scores > 11 , there was a mean change in GDS score of −5.6±SD 3.9 for intervention participants ( n=13 ) and −3.4±SD 4.5 for control participants ( n=21 ) . Adjusting for differences in baseline characteristics between groups did not affect results . CONCLUSIONS : We were unable to demonstrate any benefit from case-finding for depression during 2 years of follow-up in elderly primary care patients . Studies are needed to determine whether case-finding combined with more intensive patient education and follow-up will improve outcomes of primary care patients with depression BACKGROUND High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression . OBJECTIVE To determine the impact of offering a systematic primary care-based depression treatment program to depressed " high utilizers " not in active treatment . DESIGN R and omized clinical trial . SETTING One hundred sixty-three primary care practice s in 3 health maintenance organizations located in different geographic regions of the United States . PATIENTS A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process . Eligibility criteria were met by 410 patients and 407 agreed to enroll : 218 in the depression management program ( DMP ) practice s and 189 in the usual care ( UC ) group . INTERVENTION The DMP included patient education material s , physician education programs , telephone-based treatment coordination , and antidepressant pharmacotherapy initiated and managed by patients ' primary care physicians . MAIN OUTCOME MEASURES Depression severity was measured using the Hamilton Depression Rating Scale ( Ham-D ) and functional status using the Medical Outcomes Study 20-item short form ( SF-20 ) subscales . Outpatient visit and hospitalization rates were measured using the health plan 's encounter data . RESULTS Based on an intent-to-treat analysis , at least 3 antidepressant prescriptions were filled in the first 6 months by 151 ( 69.3 % ) of 218 of DMP patients vs 35 ( 18.5 % ) of 189 in UC ( P < .001 ) . Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks ( P = .04 ) , 3 months ( P = .02 ) , 6 months ( P < .001 ) , and 12 months ( P < .001 ) . At 12 months , DMP intervention patients were more improved than UC patients on the mental health , social functioning , and general health perceptions scales of the SF-20 ( P < .05 for all ) . CONCLUSION In depressed high utilizers not already in active treatment , a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment , decrease depression severity , and improve general health status compared with usual care Abstract OBJECTIVE : To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression . DESIGN : Following stratification , 6 of 12 practice s were r and omly assigned to the intervention condition . Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales . SETTING : Twelve community primary care practice s across the country employing no onsite mental health professional . PATIENTS : Using two-stage screening , practice s enrolled 479 depressed adult patients ( 73.4 % of those eligible ) ; 90.2 % completed six-month follow-up . INTERVENTION : Two primary care physicians , one nurse , and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression . MAIN RESULTS : In patients beginning a new treatment episode , the intervention improved depression symptoms by 8.2 points ( 95 % confidence interval [ CI ] , 0.2 to 16.1 ; P=.04 ) . Within this group , the intervention improved depression symptoms by 16.2 points ( 95 % CI , 4.5 to 27.9 ; P=.007 ) , physical role functioning by 14.1 points ( 95 % CI , 1.1 to 29.2 ; P=.07 ) , and satisfaction with care ( P=.02 ) for patients who reported antidepressant medication was an acceptable treatment at baseline . Patients already in treatment at enrollment did not benefit from the intervention . CONCLUSIONS : In practice s without onsite mental health professionals , brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode . Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition . More research is needed to determine how primary care teams can best sustain these redefined roles over time This study set out to assess the effects on diagnosis and management of providing general practitioners with feedback of patients ' scores on a depression screening instrument . One hundred and sixteen general practice attenders aged 16 - 64 with undetected depression were identified using the Beck Depression Inventory ( BDI ) . The BDI scores of a r and om 45 % were disclosed to the general practitioners . Subjects and medical casenotes were review ed over 12 months . Thirty-one ( 27 % ) of subjects were later diagnosed as depressed . Rates of diagnosis were higher in the disclosed group , but only after six months . Rates of intention to treat were low , but were marginally higher for the disclosed group ; they were much higher for patients diagnosed by the doctors themselves . Feedback of screening question naire results appears to be of limited value in enhancing general practitioners ' detection or management of depression PURPOSE Depression is a highly prevalent , morbid , and costly illness that is often unrecognized and inadequately treated . Because depression question naires have the potential to improve recognition , we evaluated the accuracy and effects on primary care of two case-finding instruments compared to usual care . SUBJECTS AND METHODS The study was conducted at three university-affiliated and one community-based medical clinics . Consecutive patients were r and omly assigned to be asked a single question about mood , to fill out the 20-item Center for Epidemiologic Studies Depression Screen , or to usual care . Within 72 hours , patients were assessed for Diagnostic and Statistical Manual of Mental Disorders Third Revised Edition ( DSM-III-R ) disorders by an assessor blinded to the screening results . Process of care was assessed using chart audit and administrative data bases ; patient and physician satisfaction was assessed using Likert scales . At 3 months , depressed patients and a r and om sample of nondepressed patients were re-assessed for DSM-III-R disorders and symptom counts . RESULTS We approached 1,083 patients , of whom 969 consented to screening and were assigned to the single question ( n = 330 ) , 20-item question naire ( n = 323 ) , or usual care ( n = 316 ) . The interview for DSM-III-R diagnosis was completed in 863 ( 89 % ) patients ; major depression , dysthymia , or minor depression was present in 13 % . Both instruments were sensitive , but the 20-item question naire was more specific than the single question ( 75 % vs 66 % , P = 0.03 ) . The 20-item question naire was less likely to be self-administered ( 54 % vs 90 % ) and took significantly more time to complete ( 15 vs 248 seconds ) . Case-finding with the 20-item question naire or single question modestly increased depression recognition , 30/77 ( 39 % ) compared with 11/38 ( 29 % ) in usual care ( P = 0.31 ) but did not affect treatment ( 45 % vs 43 % , P = 0.88 ) . Effects on DSM-III-R symptoms were mixed . Recovery from depression was more likely in the case-finding than usual care groups , 32/67 ( 48 % ) versus 8/30 ( 27 % , P = 0.03 ) , but the mean improvement in depression symptoms did not differ significantly ( 1.6 vs 1.5 symptoms , P = 0.21 ) . CONCLUSIONS A simple question about depression has similar performance characteristics as a longer 20-item question naire and is more feasible because of its brevity . Case-finding leads to a modest increase in recognition rates , but does not have consistently positive effects on patient outcomes BACKGROUND Mental health concerns are common in primary care patients and are often inadequately addressed by primary care physicians . OBJECTIVE To assess the impact of screening for mental disorders in internal medicine patients . METHODS R and omly selected patients ( n = 358 ) visiting physicians in 2 firms of an urban academic internal medicine clinic were screened for mental disorders using the 16-item Symptom-Driven Diagnostic System for Primary Care ( Upjohn Co , Kalamazoo , Mich ) first-stage screening question naire . In the experimental firm , physicians received the screening results and then administered second-stage diagnostic modules . In the control firm , physicians were not notified of the results of the screening question naire . Baseline and 3-month function were assessed using the SF-36 Health Survey , the Zung Self-Rating Depression Scale , and the Sheehan Patient-Rated Anxiety Scale . Patient satisfaction and health care utilization were also assessed by question naire at baseline and after 3 months . RESULTS Patients screening positively for any mental disorder ( n = 238 , 66.5 % ) had markedly lower baseline functional status than those screening negatively ( P < .05 on all 8 SF-36 Health Survey subscales ) and more total ( + /- SD ) outpatient visits over 3 months ( 4.5 + /- 5.5 vs 2.5 + /- 2.6 visits , P = .001 ) . Among patients who screened positively , functional outcomes and patient satisfaction were similar in experimental and control groups ; mean utilization ( + /- SD ) was lower in the experimental group ( 3.7 + /- 3.9 vs 5.3 + /- 6.7 total outpatient visits at 3 months , P = .06 ; 0.9 + /- 1.5 vs 2.1 + /- 3.7 visits to non-mental health specialists , P = .003 ; 0.2 + /- 0.5 vs 0.4 + /- 0.9 x-ray films per patient , P = .01 ) . The follow-up response rate was 286 ( 79.9 % ) of 358 patients . CONCLUSIONS The 16-item first-stage Symptom-Driven Diagnostic System for Primary Care screening question naire for mental disorders can identify primary care patients who are at risk for lower functional status and higher utilization . Use of the Symptom-Driven Diagnostic System for Primary Care second-stage diagnostic modules in patients who screened positively for mental disorders was associated with lower utilization rates but had no impact on functional outcome or patient satisfaction after 3 months OBJECTIVE Facilitate primary care physicians ' compliance with recommended st and ards of care for late life depression by reducing barriers to recognition and treatment . DESIGN R and omized controlled clinical trial of physician-targeted interventions . SETTING Academic primary care group practice caring for an urban , medically indigent patient population . PATIENTS / PARTICIPANTS Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale ( CES-D ) and the Hamilton Depression Rating Scale ( HAM-D ) and their primary care physicians . INTERVENTION Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient 's symptoms of depression . In general , physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis , discontinue medications that can cause or exacerbate depressive symptoms , initiate antidepressants when appropriate , and consider referral to psychiatry . Guidelines for prescribing antidepressants were provided . Control physicians received no intervention , and control patients received usual care . MAIN OUTCOME MEASURES Frequency of recording a depression diagnosis , stopping medications associated with depression , initiating antidepressant medication , and psychiatry referral ; mean changes in HAM-D and Sickness Impact Profile ( SIP ) scores . RESULTS One hundred three physicians and 175 patients were involved in the clinical trial . Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants ( P < 0.01 ) . There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry . Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients . Although both groups showed improvement in HAM-D and SIP scores , we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups . CONCLUSIONS Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians . However , we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians . Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care |
11,106 | 30,054,340 | Thus , the effect sizes suggesting less muscle soreness with antioxidant supplementation were very unlikely to equate to meaningful or important differences in practice .
There is moderate to low- quality evidence that high-dose antioxidant supplementation does not result in a clinical ly relevant reduction of muscle soreness after exercise of up to 6 hours or at 24 , 48 , 72 and 96 hours after exercise .
There is no evidence available on subjective recovery and only limited evidence on the adverse effects of taking antioxidant supplements | OBJECTIVE To determine whether antioxidant supplements and antioxidant-enriched foods can prevent or reduce delayed-onset muscle soreness after exercise . | There is no consensus regarding the effects of mixed antioxidant vitamin C and /or vitamin E supplementation on oxidative stress responses to exercise and restoration of muscle function . Thirty-eight men were r and omly assigned to receive either placebo group ( n = 18 ) or mixed antioxidant ( primarily vitamin C & E ) supplements ( n = 20 ) in a double-blind manner . After 6 weeks , participants performed 90 min of intermittent shuttle-running . Peak isometric torque of the knee flexors/extensors and range of motion at this joint were determined before and after exercise , with recovery of these variables tracked for up to 168 h post-exercise . Antioxidant supplementation elevated pre-exercise plasma vitamin C ( 93 ± 8 μmol l−1 ) and vitamin E ( 11 ± 3 μmol l−1 ) concentrations relative to baseline ( P < 0.001 ) and the placebo group ( P ≤ 0.02 ) . Exercise reduced peak isometric torque ( i.e. 9–19 % relative to baseline ; P ≤ 0.001 ) , which persisted for the first 48 h of recovery with no difference between treatment groups . In contrast , changes in the urine concentration of F2-isoprostanes responded differently to each treatment ( P = 0.04 ) , with a tendency for higher concentrations after 48 h of recovery in the supplemented group ( 6.2 ± 6.1 vs. 3.7 ± 3.4 ng ml−1 ) . Vitamin C & E supplementation also affected serum cortisol concentrations , with an attenuated increase from baseline to the peak values reached after 1 h of recovery compared with the placebo group ( P = 0.02 ) and serum interleukin-6 concentrations were higher after 1 h of recovery in the antioxidant group ( 11.3 ± 3.4 pg ml−1 ) than the placebo group ( 6.2 ± 3.8 pg ml−1 ; P = 0.05 ) . Combined vitamin C & E supplementation neither reduced markers of oxidative stress or inflammation nor did it facilitate recovery of muscle function after exercise-induced muscle damage ABSTRACT This investigation determined the efficacy of black currant nectar ( BCN ) in reducing symptoms of exercise-induced muscle damage ( EIMD ) . Sixteen college students were r and omly assigned to drink either 16 oz of BCN or a placebo ( PLA ) twice a day for eight consecutive days . A bout of eccentric knee extensions ( 3 × 10 sets @ 115 % of 1RM ) was performed on the fourth day . Outcome measures included muscle soreness ( subjective scale from 0 to 10 ) and blood markers of muscle damage ( creatine kinase , CK ) , inflammation ( interleukin-6 , IL-6 ) , and oxygen radical absorbance capacity ( ORAC ) . Although there were no differences in reported soreness between groups , consumption of BCN reduced CK levels at both 48 ( PLA = 82.13 % vs. BCN = −6.71 % , p = .042 ) and 96 h post exercise ( PLA = 74.96 % vs. BCN = −12.11 % , p = .030 ) . The change in IL-6 was higher in the PLA group ( PLA = 8.84 % vs. BCN = −6.54 % , p = .023 ) at 24 h post exercise . The change in ORAC levels was higher in the treatment group ( BCN = 2.68 % vs. PLA = −6.02 % , p = .039 ) at 48 h post exercise . Our results demonstrate that consumption of BCN prior to and after a bout of eccentric exercise attenuates muscle damage and inflammation Purpose Polyphenolic curcumin is known to have potent anti-inflammatory effects ; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise . Methods Fourteen untrained young men ( 24 ± 1 years ) performed 50 maximal isokinetic ( 120 ° /s ) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later . They took 150 mg of curcumin ( theracurmin ) or placebo ( starch ) orally before and 12 h after each eccentric exercise bout in a r and omised , crossover design . Maximal voluntary contraction ( MVC ) torque of the elbow flexors , range of motion of the elbow joint , upper-arm circumference , muscle soreness , serum creatine kinase ( CK ) activity , and plasma interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) concentration were measured before , immediately after , and 24 , 48 , 72 and 96 h after each eccentric exercise . Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA . Results MVC torque decreased smaller and recovered faster ( e.g. , 4 days post-exercise : −31 ± 13 % vs. −15 ± 15 % ) , and peak serum CK activity was smaller ( peak : 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L ) for curcumin than placebo condition ( P < 0.05 ) . However , no significant differences between conditions were evident for other variables , and no significant changes in IL-6 and TNF-α were evident after exercise . Conclusion It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase The aim of this study was to investigate whether post-exercise vitamin C supplementation influences recovery from an unaccustomed bout of exercise . Sixteen male subjects were allocated to either a placebo ( P ; n=8 ) or vitamin C ( VC ) group ( n=8 ) . Subjects performed a prolonged ( 90-min ) intermittent shuttle-running test , and supplementation began after the cessation of exercise . Immediately after exercise the VC group consumed 200 mg of VC dissolved in a 500 ml drink , whereas the subjects in the P group consumed the drink alone . Later on the same day and then in the morning and evening of the following 2 days , subjects consumed additional identical drinks . Plasma VC concentrations in the VC group increased above those in the P group 1 h after exercise and remained above P values for the 3 days after exercise . Nevertheless , post-exercise VC supplementation was not associated with improved recovery . Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation . Muscle soreness and the recovery of muscle function in the leg flexors and extensors were not different in VC and P groups . Furthermore , although plasma concentrations of interleukin-6 and malondialdehyde increased following exercise , there was no difference between VC and P groups . These results suggest that either free radicals are not involved in delaying the recovery process following a bout of unaccustomed exercise , or that the consumption of VC wholly after exercise is unable to deliver this antioxidant to the appropriate sites with sufficient expediency to improve recovery PURPOSE Dietary supplementation with polyphenols , particularly ellagitannins , may attenuate the muscular damage experienced after eccentric exercise , producing delayed-onset muscle soreness . The purpose of this study was to determine whether ellagitannin supplementation from Wonderful variety pomegranate extract ( POMx ) improved recovery of skeletal muscle strength after eccentric exercise . METHODS Recreationally active males were r and omized into a crossover design with either pomegranate extract ( POMx ) or placebo ( PLA ) , each given during a period of 9 d . To produce delayed-onset muscle soreness , subjects performed two sets of 20 maximal eccentric elbow flexion exercises with one arm . Maximal isometric elbow flexion strength and muscle soreness as well as serum measures of creatine kinase , myoglobin , interleukin 6 , and C-reactive protein were made at baseline and 2 , 24 , 48 , 72 , and 96 h after exercise . RESULTS With both treatments , strength was similarly reduced 2 h after exercise ( i.e. , 72 % of baseline ) , and recovery of strength was incomplete after 96 h ( i.e. , 91 % of baseline).However , strength was significantly higher in POMx compared with that in PLA at 48 h ( 85.4 % + /- 2.5 % and 78.3 % + /- 2.6 % , P = 0.01 ) and 72 h ( 88.9 % + /- 2.0 % and 84.0 % + /- 2.0 % , P = 0.009 ) after exercise . Serum markers of inflammation and muscle damage did not provide insight regarding possible mechanisms . CONCLUSIONS Supplementation with ellagitannins from pomegranate extract significantly improves recovery of isometric strength 2 - 3 d after a damaging eccentric exercise The objective of the study was to verify the effect of N-acetylcysteine ( NAC ) supplementation on parameters of oxidative damage and inflammatory response after high-intensity eccentric exercise ( EE ) . 29 participants with a mean age of 21.3+/-4 yr , weight of 74.5+/-7.7 kg , and height of 177.2+/-6.9 cm were selected and divided r and omly into 3 groups : placebo ( 21 days ; n=8 ) , NAC ( 21 days ; n=9 ) , and NAC plus placebo ( 14 days ; n=8 ) . Four participants withdrew from the study for personal reasons . 14 days after starting supplementation , the participants performed EE : 3 sets until exhaustion ( elbow flexion and extension on the Scott bench , 80 % 1RM ) . Blood sample s were collected before and on the 2nd , 4th , and 7th day after EE . Muscle soreness ( MS ) , lipoperoxidation , protein carbonylation , tumor-necrosis factor- ( TNF- ) , and interleukin 10 ( IL-10 ) were determined . Results showed a significant increase in MS in all the groups on the 2nd day after EE and a decrease in the following days . A significant increase was observed in malondialdehyde and carbonyl levels on the 4th and 7th days after EE in all groups . TNF- increased significantly on the 2nd day after eccentric exercise and decreased in the following days irrespective of NAC supplementation ; concentration of IL-10 increased significantly on the 4th day in all groups . Only the supplemented groups maintained high levels of IL-10 on the 7th day after EE . The results suggest that treatment with NAC represents an important factor in the defense against muscle soreness and has different effects on oxidative damage and pro- and anti-inflammatory cytokines Background Delayed onset muscle soreness ( DOMS ) due to eccentric muscle activity is associated with inflammatory responses and production of reactive oxygen species ( ROS ) that sustain both inflammation and oxidative stress . Curcumin , a powerful promoter of anti-oxidant response , is one of the best-investigated natural products , and is now commercially available as a lecithin delivery system ( Meriva ® , Indena SpA , Milan ) with improved bio-availability . The aim of this study was to test whether curcumin could attenuate damage from oxidative stress and inflammation related to acute muscle injury induced by eccentric continuous exercise Methods This was a r and omised , placebo-controlled , single-blind pilot trial . Twenty male healthy , moderately active volunteers were r and omised to curcumin given as the Phytosome ® delivery system 1 g twice daily ( 200 mg curcumin b.i.d . ) or matching placebo . Supplementation was initiated 48 hours prior to a downhill running test and was continued for 24 hours after the test ( 4 days in total ) . Muscle damage was quantified by magnetic resonance imaging , laboratory tests and histological analyses on muscle sample s obtained 48 hours after the test . Patient-reported pain intensity was also recorded . Results Subjects in the curcumin group reported less pain in the lower limb as compared with subjects in the placebo group , although significant differences were observed only for the right and left anterior thighs . Significantly fewer subjects in the curcumin group had MRI evidence of muscle injury in the posterior or medial compartment of both thighs . Increases in markers of muscle damage and inflammation tended to be lower in the curcumin group , but significant differences were only observed for interleukin-8 at 2 h after exercise . No differences in markers of oxidative stress and muscle histology were observed Conclusions Curcumin has the potential for preventing DOMS , as suggested by its effects on pain intensity and muscle injury . Larger studies are needed to confirm these results and further clarify the mechanism of action of curcumin Background Both acute bouts of prior exercise ( preconditioning ) and antioxidant nutrients have been used in an attempt to attenuate muscle injury or oxidative stress in response to resistance exercise . However , most studies have focused on untrained participants rather than on athletes . The purpose of this work was to determine the independent and combined effects of antioxidant supplementation ( vitamin C + mixed tocopherols/tocotrienols ) and prior eccentric exercise in attenuating markers of skeletal muscle injury and oxidative stress in resistance trained men . Methods Thirty-six men were r and omly assigned to : no prior exercise + placebo ; no prior exercise + antioxidant ; prior exercise + placebo ; prior exercise + antioxidant . Markers of muscle/cell injury ( muscle performance , muscle soreness , C-reactive protein , and creatine kinase activity ) , as well as oxidative stress ( blood protein carbonyls and peroxides ) , were measured before and through 48 hours of exercise recovery . Results No group by time interactions were noted for any variable ( P > 0.05 ) . Time main effects were noted for creatine kinase activity , muscle soreness , maximal isometric force and peak velocity ( P < 0.0001 ) . Protein carbonyls and peroxides were relatively unaffected by exercise . Conclusion There appears to be no independent or combined effect of a prior bout of eccentric exercise or antioxidant supplementation as used here on markers of muscle injury in resistance trained men . Moreover , eccentric exercise as used in the present study results in minimal blood oxidative stress in resistance trained men . Hence , antioxidant supplementation for the purpose of minimizing blood oxidative stress in relation to eccentric exercise appears unnecessary in this population PURPOSE Vitamin E supplementation may confer a protective effect against eccentrically biased exercise-induced muscle damage through stabilization of the cell membrane and possibly via inhibition of free radical formation . Evidence supporting a protective role of vitamin E after contraction-induced muscle injury in humans is , however , inconsistent . The present study sought to determine the effect of vitamin E supplementation on indices of exercise-induced muscle damage and the postexercise inflammatory response after performance of repeated eccentric muscle contractions . METHODS Young healthy men performed a bout of 240 maximal isokinetic eccentric muscle contractions ( 0.52 rad.s-1 ) after being supplemented for 30 d with either vitamin E ( N = 9 ; 1200 IU.d-1 ) or placebo ( N = 7 ; safflower oil ) . RESULTS Measurements of torque ( isometric and concentric ) decreased ( P < 0.05 ) below preexercise values immediately post- and at 48 h post-exercise . Biopsies taken 24 h postexercise showed a significant increase in the amount of extensive Z-b and disruption ( P < 0.01 ) ; however , neither the torque deficit nor the extent of Z-b and disruption were affected by vitamin E. Exercise result ed in increased macrophage cell infiltration ( P = 0.05 ) into muscle , which was also unaffected by vitamin E. Serum CK also increased as a result of the exercise ( P < 0.05 ) with no effect of vitamin E. CONCLUSION We conclude that vitamin E supplementation ( 30 d at 1200 IU.d-1 ) , which result ed in a 2.8-fold higher serum vitamin E concentration ( P < 0.01 ) , had no affect on indices of contraction-induced muscle damage nor inflammation ( macrophage infiltration ) as a result of eccentrically biased muscle contractions Background Exercise-induced muscle damage ( EIMD ) is accompanied by localized oxidative stress / inflammation which , in the short-term at least , is associated with impaired muscular performance . Dietary antioxidants have been shown to reduce excessive oxidative stress ; however , their effectiveness in facilitating recovery following EIMD is not clear . Blueberries demonstrate antioxidant and anti-inflammatory properties . In this study we examine the effect of New Zeal and blueberries on EIMD after strenuous eccentric exercise . Methods In a r and omized cross-over design , 10 females consumed a blueberry smoothie or placebo of a similar antioxidant capacity 5 and 10 hours prior to and then immediately , 12 and 36 hours after EIMD induced by 300 strenuous eccentric contractions of the quadriceps . Absolute peak and average peak torque across the knee , during concentric , isometric , and eccentric actions were measured . Blood biomarkers of oxidative stress , antioxidant capacity , and inflammation were assessed at 12 , 36 and 60 hours post exercise . Data were analyzed using a two-way ANOVA . Results A significant ( p < 0.001 ) decrease in isometric , concentric and eccentric torque was observed 12 hours following exercise in both treatment groups . During the 60 hour recovery period , a significant ( p = 0.047 ) interaction effect was seen for peak isometric tension suggesting a faster rate of recovery in the blueberry intervention group . A similar trend was observed for concentric and eccentric strength . An increase in oxidative stress and inflammatory biomarkers was also observed in both treatment groups following EIMD . Although a faster rate of decrease in oxidative stress was observed in the blueberry group , it was not significant ( p < 0.05 ) until 36 hours post-exercise and interestingly coincided with a gradual increase in plasma antioxidant capacity , whereas biomarkers for inflammation were still elevated after 60 hours recovery . Conclusions This study demonstrates that the ingestion of a blueberry smoothie prior to and after EIMD accelerates recovery of muscle peak isometric strength . This effect , although independent of the beverage ’s inherent antioxidant capacity , appears to involve an up-regulation of adaptive processes , i.e. endogenous antioxidant processes , activated by the combined actions of the eccentric exercise and blueberry consumption . These findings may benefit the sporting community who should consider dietary interventions that specifically target health and performance adaptation We have previously shown that vitamin C supplementation affects recovery from an unaccustomed bout of dem and ing exercise , with the most pronounced effect being that on plasma interleukin-6 concentration . However , because of the proposed role of interleukin-6 in the regulation of metabolism , it was unclear whether this represented a reduced response to muscle damage or some form of interaction with the metabolic dem and s of the activity . Therefore , the aim of the present study was to investigate the effect of the same form of supplementation on a bout of exercise that initiated similar muscle damage but had a low metabolic cost . Fourteen male subjects were allocated to either a placebo ( P ) or a vitamin C ( VC ) group . The VC group consumed 200 mg of ascorbic acid twice a day for 14 days prior to a bout of exercise and for the 3 days after exercise . The P group consumed identical capsules that contained 200 mg lactose . Subjects performed 30 min of downhill running at a gradient of −18 % and recovery was monitored for up to 3 days after exercise . Plasma VC concentrations in the VC group increased following supplementation . Nevertheless , downhill running provoked a similar increase in circulating markers of muscle damage ( creatine kinase activity and myoglobin concentration ) and muscle soreness in P and VC groups . Similarly , although downhill running increased plasma interleukin-6 , there was no effect from VC supplementation . These results suggest that vitamin C supplementation does not affect interleukin-6 concentrations following eccentric exercise that has a low metabolic component Background Long distance running causes acute muscle damage result ing in inflammation and decreased force production . Endurance athletes use NSAIDs during competition to prevent or reduce pain , which carries the risk of adverse effects . Tart cherries , rich in antioxidant and anti-inflammatory properties , may have a protective effect to reduce muscle damage and pain during strenuous exercise . This study aim ed to assess the effects of tart cherry juice as compared to a placebo cherry drink on pain among runners in a long distance relay race . Methods The design was a r and omized , double blind , placebo controlled trial . Fifty-four healthy runners ( 36 male , 18 female ; 35.8 ± 9.6 yrs ) ran an average of 26.3 ± 2.5 km over a 24 hour period . Participants ingested 355 mL bottles of tart cherry juice or placebo cherry drink twice daily for 7 days prior to the event and on the day of the race . Participants assessed level of pain on a st and ard 100 mm Visual Analog Scale ( VAS ) at baseline , before the race , and after the race . Results While both groups reported increased pain after the race , the cherry juice group reported a significantly smaller increase in pain ( 12 ± 18 mm ) compared to the placebo group ( 37 ± 20 mm ) ( p < .001 ) . Participants in the cherry juice group were more willing to use the drink in the future ( p < 0.001 ) and reported higher satisfaction with the pain reduction they attributed to the drink ( p < 0.001 ) . Conclusions Ingesting tart cherry juice for 7 days prior to and during a strenuous running event can minimize post-run muscle pain PURPOSE This study investigated the effects of a dietary supplement on exercise-induced markers of cell damage and the inflammatory mediators C-reactive protein ( CRP ) and interleukin-6 ( IL-6 ) . METHODS The supplement contained mixed tocopherols , flavonoids , and docosahexaenoate . Forty healthy , nonsmoking , untrained males ( aged 18 - 35 yr ) were r and omly assigned to receive either the supplement ( N = 20 ) or placebo ( N = 20 ) during the 14-d experimental protocol . Blood sample s were collected on day 0 ( baseline ) , day 7 ( eccentric exercise-induced injury ) , day 10 , and day 14 . OBJECTIVE Markers of cell damage ( creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) ) and inflammation IL-6 and CRP were assessed at these time points in conjunction with subjective range of motion ( ROM ) and perceived pain measurements . Statistical analyses were conducted using nonparametric methods ( P < 0.05 ) . RESULTS Eccentric arm curl exercise was used to induce an acute phase injury response as evidence d by significant ( P < 0.0001 ) increases in CK , LDH , and pain , as well as a decreased range of motion 3 d after the exercise . There were no significant differences between groups in CK and LDH responses . In contrast , there were significant group differences for IL-6 ( P = 0.008 ) and CRP ( P = 0.003 ) . At day 10 , by Mann-Whitney U test of changes , the placebo group had significantly greater increases in IL-6 and CRP than the treatment group ( P = 0.05 and P < 0.01 ) , respectively . CONCLUSION This study suggested that exercise-induced inflammation , evaluated by changes in IL-6 and CRP , was significantly reduced by the dietary supplement The purpose of this study was to investigate the effects of vitamin E supplementation on muscular and oxidative damage , as well as the inflammatory response induced by eccentric exercise ( EE ) in humans . Twenty-one participants with a mean age of 22.5 ± 4 years , weight of 68.2 ± 4.9 kg , and height of 173 ± 4.3 cm were selected and divided r and omly into two groups : supplemented ( S ) ( n = 11 ) and placebo ( P ) ( n = 10 ) . Fourteen days after starting supplementation , subjects performed EE ( three sets until exhaustion with elbow flexion and extension on the Scott bench , 80 % 1 RM ) . Blood sample s were collected on days 0 , 2 , 4 , and 7 after EE . Muscle soreness ( MS ) , lactate dehydrogenase ( LDH ) activity , lipid peroxidation , protein carbonylation , tumor necrosis factor-α ( TNF-α ) , and interleukin 10 ( IL-10 ) levels were determined . We measured a significant increase in MS , LDH , lipid peroxidation , and carbonylation in both groups on days 2 , 4 , and 7 after eccentric contractions ( EC ) . Values of the supplement group were lower than those of the placebo group at 4 and 7 days after EC in all parameters . Both groups showed significantly increased TNF-α on the second day and IL-10 concentration on the fourth and seventh days after EE . The results suggest that vitamin E supplementation represents an important factor in the defense against oxidative stress and muscle damage but not against the inflammatory response in humans Background Tart Montmorency cherries contain high concentrations of phytochemicals and anthocyanins , which have recently been linked to improved athletic recovery and subsequent performance . To date however , previous work reporting promising results has focused on l and -based endurance sports , with any potential benefits to team sports remaining unknown . As such , this investigation set-out to examine the effect of supplemental tart cherry juice ( CJ ) on recovery and next day athletic performance in highly-trained water-based team sport athletes over seven days . Methods In a r and omised , double-blind , repeated measures , crossover design , nine male Water Polo athletes were supplemented with CJ or a placebo equivalent ( PLA ) for six consecutive days . Prior to , and at the completion of the supplementation period , water-based performance testing was conducted . On day 6 , participants also undertook a fatiguing simulated team game activity . Venous blood sample s were collected ( Pre-exercise : day 1 , 6 and 7 ; Post-exercise : day 6 ) to investigate markers of inflammation [ Interleukin-6 ( IL-6 ) ; C-reactive protein ( CRP ) ] and oxidative stress [ Uric Acid ( UA ) ; F2-Isoprostane ( F2-IsoP ) ] . A daily diary was also completed ( total quality of recovery , delayed onset muscle soreness ) as a measure of perceptual recovery . Results In both conditions , day 6 post-exercise IL-6 was significantly higher than pre-exercise and day 7 ( p < 0.05 ) ; CRP was greater on day 7 as compared to day 6 pre- and post-exercise ( p < 0.05 ) ; F2-IsoP was significantly lower on day 7 as compared to day 1 and day 6 ( p < 0.05 ) ; UA remained unchanged ( p > 0.05 ) . No differences were found for any performance or recovery measures . Conclusions The lack of difference observed in the blood markers between groups may reflect the intermittent , non-weight bearing dem and s of Water Polo , with such activity possibly unable to create a substantial inflammatory response or oxidative stress ( over 7 days ) to impede performance ; thereby negating any potential beneficial effects associated with CJ supplementation . Trial registration This trial was registered with the Australian and New Zeal and Clinical Trials Registry ( ANZCTR ) . Registration number : ACTRN12616001080415 . Date registered : 11/08/2016 , retrospectively registered Introduction Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice . Purpose To determine effects of curcumin on muscle damage , inflammation and delayed onset muscle soreness ( DOMS ) in humans . MethodS eventeen men completed a double-blind r and omized-controlled crossover trial to estimate the effects of oral curcumin supplementation ( 2.5 g twice daily ) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise . Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise , separated by 14-d washout . Measurements were made at baseline , and 0 , 24 and 48-h post-exercise comprising : ( a ) limb pain ( 1–10 cm visual analogue scale ; VAS ) , ( b ) muscle swelling , ( c ) single-leg jump height , and ( d ) serum markers of muscle damage and inflammation . St and ardized magnitude-based inference was used to define outcomes . Results At 24 and 48-h post-exercise , curcumin caused moderate-large reductions in pain during single-leg squat ( VAS scale −1.4 to −1.7 ; 90 % CL : ±1.0 ) , gluteal stretch ( −1.0 to −1.9 ; ±0.9 ) , squat jump ( −1.5 to −1.1 ; ± 1.2 ) and small reductions in creatine kinase activity ( −22–29 % ; ±21–22 % ) . Associated with the pain reduction was a small increase in single-leg jump performance ( 15 % ; 90 % CL ± 12 % ) . Curcumin increased interleukin-6 concentrations at 0-h ( 31 % ; ±29 % ) and 48-h ( 32 % ; ±29 % ) relative to baseline , but decreased IL-6 at 24-h relative to post-exercise ( −20 % ; ±18 % ) . Conclusions Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance . Further study is required on mechanisms and translational effects on sport or vocational performance Dietary flavanols have been associated with reduced oxidative stress , however their efficacy in promoting recovery after exercise induced muscle damage is unclear . This study examined the effectiveness of acute consumption of cocoa-flavanols on indices of muscle recovery including : subsequent exercise performance , creatine kinase , muscle tenderness , force , and self-perceived muscle soreness . Eight endurance-trained athletes ( VO2max 64.4 ± 7.6 mL/kg/min ) completed a downhill running protocol to induce muscle soreness , and 48-h later completed a 5-K ( kilometer ) time trial . Muscle recovery measurements were taken at PRE , 24 h-POST , 48 h-POST , and POST-5 K . Participants consumed 1.0 g of carbohydrate per kilogram of body weight of a r and omly assigned beverage ( CHOC : 0 mg flavanols vs. CocoaCHOC : 350 mg flavanols per serving ) immediately after the downhill run and again 2 h later . The same protocol was repeated three weeks later with the other beverage . An ANOVA revealed no significant difference ( p = 0.97 ) between trials for 5 K completion time ( CHOC 1198.3 ± 160.6 s , CocoaCHOC 1195.5 ± 148.8 s ) . No significant difference was found for creatine kinase ( CK ) levels ( p = 0.31 ) , or muscle soreness ( p = 0.21 ) between groups over time . These findings suggest that the acute addition of cocoa flavanols to low-fat chocolate milk offer no additional recovery benefits Background Exercise-Induced Muscle Damage ( EIMD ) and delayed onset muscle soreness ( DOMS ) impact subsequent training sessions and activities of daily living ( ADL ) even in active individuals . In sedentary or diseased individuals , EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise . Methods The purpose of this study was to determine the effects of oral curcumin supplementation ( Longvida ® 400 mg/days ) on muscle & ADL soreness , creatine kinase ( CK ) , and inflammatory cytokines ( TNF-α , IL-6 , IL-8 , IL-10 ) following EMID ( eccentric-only dual-leg press exercise ) . Subjects ( N = 28 ) were r and omly assigned to either curcumin ( 400 mg/day ) or placebo ( rice flour ) and supplemented 2 days before to 4 days after EMID . Blood sample s were collected prior to ( PRE ) , and 1 , 2 , 3 , and 4 days after EIMD to measure CK and inflammatory cytokines . Data were analyzed by ANOVA with P < 0.05 . Results Curcumin supplementation result ed in significantly smaller increases in CK ( − 48 % ) , TNF-α ( − 25 % ) , and IL-8 ( − 21 % ) following EIMD compared to placebo . We observed no significant differences in IL-6 , IL-10 , or quadriceps muscle soreness between conditions for this sample size . Conclusions Collectively , the findings demonstrated that consumption of curcumin reduced biological inflammation , but not quadriceps muscle soreness , during recovery after EIMD . The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions . General significance These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD . The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model The flavonoid quercetin is purported to have potent antioxidant and anti-inflammatory properties . This study examined if quercetin supplementation attenuates indicators of exercise-induced muscle damage in a double-blind laboratory study . Thirty healthy subjects were r and omized to quercetin ( QU ) or placebo ( PL ) supplementation and performed 2 separate sessions of 24 eccentric contractions of the elbow flexors . Muscle strength , soreness , resting arm angle , upper arm swelling , serum creatine kinase ( CK ) activity , plasma quercetin ( PQ ) , interleukin-6 ( IL-6 ) , and C-reactive protein ( CRP ) were assessed before and for 5 d after exercise . Subjects then ingested nutrition bars containing 1,000 mg/d QU or PL for 7 d before and 5 d after the second exercise session , using the opposite arm . PQ reached 202 ± 52 ng/ml after 7 d of supplementation and remained elevated during the 5-d postexercise recovery period ( p < .05 ) . Subjects experienced strength loss ( peak = 47 % ) , muscle soreness ( peak = 39 ± 6 mm ) , reduced arm angle ( -7 ° ± 1 ° ) , CK elevations ( peak = 3,307 ± 1,481 U/L ) , and arm swelling ( peak = 11 ± 2 mm ; p < .0001 ) , indicating muscle damage and inflammation ; however , differences between treatments were not detected . Eccentric exercise did not alter plasma IL-6 ( peak = 1.9 pg/ml ) or CRP ( peak = 1.6 mg/L ) relative to baseline or by treatment . QU supplementation had no effect on markers of muscle damage or inflammation after eccentric exercise of the elbow flexors PURPOSE This study was conducted to determine if 6 wk of supplementation with vitamins E and C could alleviate exercise-induced muscle damage . We studied 22 runners during a 50-km ultramarathon . METHODS Subjects were r and omly assigned to one of two groups : ( a ) placebos ( PL ) or ( b ) antioxidants ( AO ) ( 1000 mg vitamin C and 300 mg RRR-alpha-tocopheryl acetate ) . Blood sample s were obtained before supplementation ( baseline ) , 24 h pre- , 12 h pre- , and 1 h prerace ; midrace , postrace , 2 h postrace , and for 6 d postrace . Plasma alpha-tocopherol ( alpha-TOH ) , ascorbic acid ( AA ) , and muscle damage markers ( creatine kinase ( CK ) and lactate dehydrogenase ( LDH ) ) , as well as maximal voluntary contraction ( MVC ) of the hamstring and quadriceps were assessed . RESULTS With supplementation , plasma alpha-TOH and AA increased in the AO but not the PL group . LDH and CK increased in response to the race ; LDH peaked at postrace and CK reached maximal values 2 h and 1 d postrace ; neither was affected by treatment . Adjusting for between-subject differences in baseline CK values revealed that men had higher levels of CK than did women throughout the study . Correcting CK values for lean body mass ( kg ) eliminated sex differences , but not changes over time . CK was significantly correlated ( R = 0.52 , P < 0.0001 ) with C-reactive protein , an acute phase response marker . MVC decreased 14 - 26 % in all groups in response to the run . Eccentric hamstring ( EH ) torque and concentric quadriceps ( CQ ) power exhibited the largest deficits , 26 and 24 % , respectively , with no effect of treatment . CQ recovered at a faster rate in women than in men . CONCLUSION Antioxidants appeared to have no effect on exercise-induced increases in muscle damage or recovery , but important sex differences were observed PURPOSE This study tested the effectiveness of a fruit , berry , and vegetable concentrate ( FVC ) , Juice Plus+ ® ( NSA LLC , Collierville , TN ) , supplement on muscle function and oxidative stress in response to an acute bout of eccentric exercise ( EE ) . METHODS Forty-one healthy volunteers ( age = 18 - 35 yr ) were r and omly assigned to either a placebo ( P ) or an FVC treatment taking capsules for 28 d ( 6 d(-1 ) ) before EE and for the next 4 d. All subjects completed four sets of 12 repetitions of eccentric elbow flexion with their nondominant arm . Blood , muscle soreness ( MS ) , range of motion ( ROM ) , and maximal isometric force ( MIF ) of the elbow flexors were obtained before and immediately after exercise and at 2 , 6 , 24 , 48 , and 72 h postexercise . Plasma was analyzed for creatine kinase ( CK ) , lipid hydroperoxides , malondialdehyde ( MDA ) , and protein carbonyls ( PC ) . Glutathione ratio was determined from whole-blood extracts . RESULTS MS , ROM , MIF , and plasma CK demonstrated significant time effects independent of treatment . MS and plasma CK increased over time , whereas ROM and MIF decreased over time . There was a significant time and time × treatment effect for plasma PC and MDA . PC and MDA increased over time in the P group ( P < 0.01 ) but were not significantly altered in the FVC-treated group at any time . No significant changes were noted in lipid hydroperoxides . The glutathione ratio was elevated immediately postexercise in both groups ( P < 0.01 ) and elevated 6 h postexercise with P compared with the FVC-treated group ( P < 0.05 ) . CONCLUSION This study reports that 4 wk of pretreatment with an FVC can attenuate blood oxidative stress markers induced by EE but had no significant impact on the functional changes related to pain and muscle damage Reactive oxygen species may contribute to exercise-induced skeletal muscle damage , and antioxidants may protect against such damage . This study examined the effectiveness of prophylactic supplementation with vitamins C and E on symptoms of muscle damage in a single blind , two-group study design . Twelve male volunteers were r and omly assigned to either treatment or control groups . The treatment group received 500 mg of vitamin C and 1,200 IU of alpha−tocopherol daily and the control group received glucose placebo for 37 days . After 30 days of treatment , volunteers performed 300 maximal eccentric contractions of the knee extensor muscles of one leg . Maximal voluntary isometric contraction force and electrically evoked force at a frequency of 20 Hz and 50 Hz were recorded before and after exercise , and on days 1 , 2 and 7 after exercise . Muscle soreness question naires were completed and muscle girth recorded at the same time points . Eccentric contractile torque and work during the bout declined significantly in both groups ( P<0.001 ) , but this decline was smaller in the vitamin-supplemented group ( P<0.05 ) . Maximal voluntary isometric contraction force and 20:50 Hz force ratio declined significantly after exercise in both groups ( P<0.01 ) , but the decline was smaller in the treatment group on days 1 and 2 post-exercise ( P<0.05 ) . Both groups experienced similar significant muscle soreness and swelling after exercise . These data suggest that prior supplementation with dietary antioxidants ameliorates muscle functional decrements subsequent to eccentric muscle contraction We investigated the effect of antioxidant supplementation on markers of muscle damage , antioxidant status , and delayed onset of muscle soreness ( DOMS ) after repeated downhill runs . Moderately-trained males ( n=22 ) were r and omly assigned to a supplement ( S ) or placebo ( P ) group . Capsules ( vitamin C:1 000 mg/d ; vitamin E : 400 IU/d ) were ingested daily for 2 weeks . before the first ( 1D ) and second ( 2D ) downhill runs , and for 2 additional days following each run . Creatine kinase ( CK ) activity and oxygen radical absorbance capacity ( ORAC ) were measured pre-exercise and at 0 ( immediately ) , 6 , 24 and 48 h post-exercise ( POST ) . DOMS was rated for quadriceps , hamstring , gluteus , gastrocnemius , and tibialis anterior at 0 , 24 , 48 and 72 h POST . CK at 48 h following 1D remained elevated above pre-exercise only in P ( P<0.01 ) . Overall , DOMS of the quadriceps was lower in S ( 1.1±0.3 ) than P ( 2.2±0.5 ) ( P<0.05 ) . At 24 h POST in S , CK was lower ( P<0.01 ) and ORAC was higher ( P<0.05 ) following 2D than 1D . CK and ORAC following 2D were blunted and augmented , respectively , in response to 1D and antioxidant supplementation enhanced this protective effect as indicated by an attenuation of biomarkers of muscle damage and a greater antioxidant capacity observed 24 h POST 2D Compounds found in the skins of grapes , including catechins , quercetin , and resveratrol , have been added to the diet of rodents and improved run time to exhaustion , fitness , and skeletal-muscle mitochondrial function . It is unknown if such effects occur in humans . The purpose of this experiment was to investigate whether 6 wk of daily grape consumption influenced maximal oxygen uptake ( VO(2max ) ) , work capacity , mood , perceived health status , inflammation , pain , and arm-function responses to a mild eccentric-exercise-induced arm-muscle injury . Forty recreationally active young adults were r and omly assigned to consume a grape or placebo drink for 45 consecutive days . Before and after 42 d of supplementation , assessment s were made of treadmill-running VO(2max ) , work capacity ( treadmill performance time ) , mood ( Profile of Mood States ) , and perceived health status ( SF-36 Health Survey ) . The day after posttreatment treadmill tests were completed , 18 high-intensity eccentric actions of the nondominant elbow flexors were performed . Arm-muscle inflammation , pain , and function ( isometric strength and range of motion ) were measured before and on 2 consecutive days after the eccentric exercise . Mixed-model ANOVA showed no significant effect of grape consumption on any of the outcomes . Six weeks of supplemental grape consumption by recreationally active young adults has no effect on VO(2max ) , work capacity , mood , perceived health status , inflammation , pain , or physical-function responses to a mild injury induced by eccentric exercise To investigate the effects of allicin supplementation on exercise-induced muscle damage ( EIMD ) , interleukin-6 ( IL-6 ) , and antioxidative capacity , a double-blinded , placebo-controlled study was conducted in well-trained athletes . Subjects were r and omly assigned to an allicin supplementation group ( AS group ) and a control group , and received either allicin or placebo for 14 days before and 2 days after a downhill treadmill run . Plasma creatine kinase ( CK ) , muscle-specific creatine kinase ( CK-MM ) , lactate dehydrogenase ( LDH ) , IL-6 , superoxide dismutase ( SOD ) , total antioxidative capacity ( TAC ) , and perceived muscle soreness were measured pre and post exercise . AS group had significantly lower plasma levels of CK , CK-MM and IL-6 , and reduced perceived muscle soreness after exercise , when compared with the control group . AS group also demonstrated a trend toward reducing plasma concentration of LDH after exercise ( P = 0.08 ) , although not statistically significant . Allicin supplementation induced a higher value of TAC at rest , and this higher value was maintained 48 h after exercise , however , there was no difference in SOD values after exercise between the two groups . The results suggested that allicin might be a potential agent to reduce EIMD . Further studies concerning anti-inflammatory and anti-oxidative effects of allicin on EIMD are needed This study investigated if vitamin C supplementation before and after eccentric exercise could reduce muscle soreness ( MS ) , oxidative stress , and muscle function . Eighteen healthy men r and omly assigned to either a placebo ( P ) or vitamin C ( VC ) ( 3 g/d ) treatment group took pills for 2 wk prior and 4 d after performing 70 eccentric elbow extensions with their non-dominant arm . MS increased in both groups with significantly reduced MS for the first 24 h with VC . Range of motion was reduced equally in both groups after the exercise ( P > or = 0.05 ) . Muscle force declined equally and was unaffected by treatment . VC attenuated the creatine kinase ( CK ) increase at 48 h after exercise with similar CK after this time . Glutathione ratio ( oxidized glutathione/total glutathione ) was significantly increased at 4 and 24 h with P but VC prevented this change . These data suggest that vitamin C pretreatment can reduce MS , delay CK increase , and prevent blood glutathione oxidation with little influence on muscle function loss & NA ; Delayed‐onset muscle soreness following strenuous use of the posterior calf muscles was studied to determine if ascorbic acid might have an effect on the appearance of this familiar pain . A double‐blind , r and omized , crossover study compared the soreness in subjects taking ascorbic acid against those taking a lactose placebo . Visual analog scales were used in conjunction with a variety of pain‐challenging methods , and the results indicated a significant difference between experimental and placebo groups at the height of soreness . Typical soreness abatement scores of 25–44 % were observed . A sample size of 19 , lack of an untreated control group as well as the singular nature of the exercise and its intensity were considered limitations of the study Background : Numerous antioxidant and anti-inflammatory agents have been identified in tart cherries . Objective : To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage . Methods : This was a r and omised , placebo controlled , crossover design . Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days . A bout of eccentric elbow flexion contractions ( 2 × 20 maximum contractions ) was performed on the fourth day of supplementation . Isometric elbow flexion strength , pain , muscle tenderness , and relaxed elbow angle were recorded before and for four days after the eccentric exercise . The protocol was repeated two weeks later with subjects who took the placebo initially , now taking the cherry juice ( and vice versa ) . The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect . Results : Strength loss and pain were significantly less in the cherry juice trial versus placebo ( time by treatment : strength p<0.0001 , pain p = 0.017 ) . Relaxed elbow angle ( time by treatment p = 0.85 ) and muscle tenderness ( time by treatment p = 0.81 ) were not different between trials . Conclusions : These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage . Most notably , strength loss averaged over the four days after eccentric exercise was 22 % with the placebo but only 4 % with the cherry juice AIM The aim of this study was to compare the effects of 8 days of vitamin C ( VC ) supplementation on elbow flexor delayed onset muscle soreness ( DOMS ) to 8 days of placebo ingestion . METHODS For 3 days prior to an exercise bout ( 2 x 20 eccentric elbow extensions ) , and for 5 days after , a treatment group ingested 3 x 1000 mg/day of VC versus 3 x 50 mg/day of glucose ingestion for the placebo group over the same time period . All subjects were prescreened via dietary recall to exclude any subjects with habitual VC consumption greater than 400 mg/day . Subject comprised 24 subjects ( male and female ) r and omly divided into 2 groups of 12 subjects . Treatment group comprised 5 females and placebo group comprised 8 females . RESULTS Data from a repeated measures ANOVA indicate that DOMS was successfully induced in both groups via significant time effects for strength loss ( P = 0.0001 ) , point tenderness ( P = 0.0001 ) , elbow flexor decreased range of motion ( P = 0.013 ) , and subjective pain ( P = 0.0001 ) . However , there were no significant between group differences in response to any of the aforementioned variables : strength loss ( P = 0.202 ) , point tenderness ( P = 0.824 ) , elbow flexor range of motion ( P = 0.208 ) , subjective pain ( P = 0.342 ) . CONCLUSIONS The results of this study suggest that a VC supplementation protocol of 3 x 1000 mg/day for 8 days is ineffective in protecting against selected markers of DOMS The purpose s of this investigation were to see whether free radical production changed with high intensity resistance exercise and , secondly , to see whether vitamin E supplementation would have any effect on free radical formation or variables associated with muscle membrane disruption . Twelve recreationally weight-trained males were divided into two groups . The supplement group ( S ) received 1200 IUs of vitamin E once a day ( 3 x 400 IU x d[-1 ] ) for a period of 2 wk . The placebo group ( P ) received cellulose-based placebo pills once a day for the same period of time . Creatine kinase activity was significantly elevated between preexercise and immediately postexercise , 6 h postexercise , and 24 h postexercise for both groups . The placebo group also had a significant increase in creatine kinase activity at 48 h postexercise . There was a significant difference in creatine kinase activity between the groups at 24 h after exercise . Plasma malondialdehyde significantly increased from preexercise levels for the P group at 6 and 24 h postexercise . Plasma malondialdehyde concentrations significantly increased in the S group between preexercise and immediately postexercise levels . This study indicates that high intensity resistance exercise increases free radical production and that vitamin E supplementation may decrease muscle membrane disruption Trombold , JR , Reinfeld , AS , Casler , JR , and Coyle , EF . The effect of pomegranate juice supplementation on strength and soreness after eccentric exercise . J Strength Cond Res 25(7 ) : 1782 - 1788 , 2011—The purpose of this study was to determine if pomegranate juice supplementation improved the recovery of skeletal muscle strength after eccentric exercise in subjects who routinely performed resistance training . Resistance trained men ( n = 17 ) were r and omized into a crossover design with either pomegranate juice or placebo . To produce delayed onset muscle soreness , the subjects performed 3 sets of 20 unilateral eccentric elbow flexion and 6 sets of 10 unilateral eccentric knee extension exercises . Maximal isometric elbow flexion and knee extension strength and muscle soreness measurements were made at baseline and 2 , 24 , 48 , 72 , 96 , and 168 hours postexercise . Elbow flexion strength was significantly higher during the 2- to 168-hour period postexercise with pomegranate juice compared with that of placebo ( main treatment effect ; p = 0.031 ) . Elbow flexor muscle soreness was also significantly reduced with pomegranate juice compared with that of placebo ( main treatment effect ; p = 0.006 ) and at 48 and 72 hours postexercise ( p = 0.003 and p = 0.038 , respectively ) . Isometric strength and muscle soreness in the knee extensors were not significantly different with pomegranate juice compared with those using placebo . Supplementation with pomegranate juice attenuates weakness and reduces soreness of the elbow flexor but not of knee extensor muscles . These results indicate a mild , acute ergogenic effect of pomegranate juice in the elbow flexor muscles of resistance trained individuals after eccentric exercise The purpose of this study was to determine the effects of antioxidant therapy on indirect markers of muscle damage following eccentric exercise ( EE ) . Eighteen women were r and omized to an antioxidant supplement or a placebo before a bout of EE . Plasma creatine kinase ( CK ) activity , muscle soreness ( MS ) , maximal isometric force ( MIF ) , and range of motion ( ROM ) were assessed before and through 14 d postexercise . Eccentric exercise result ed in an increase in CK activity and MS , and a drop in MIF and ROM during the days following EE , which returned to baseline values 14 d after EE in both groups . Antioxidants attenuated the CK activity and MS response to the EE , while little difference was noted between groups in MIF or ROM . These findings suggest that antioxidant supplementation was helpful in reducing the elevations in plasma CK activity and MS , with little impact on MIF and ROM loss Exercise-induced free-radical production may be partly responsible for muscle soreness and damage following dem and ing exercise . A number of studies have investigated the effect of antioxidant supplementation although there is a paucity of information regarding vitamin C. Therefore the aim of the present study was to investigate the effect of vitamin C supplementation on exercise-induced muscle soreness and damage . Nine habitually active males consumed a 1 g dose of vitamin C 2 h before exercise , and on another occasion consumed an identical placebo . The exercise comprised a 90 min intermittent shuttle-running test , which was design ed to simulate the multiple-sprint sports . Vitamin C supplementation increased plasma concentrations of vitamin C before exercise , and plasma concentrations continued to increase during the shuttle-run to reach a peak of approximately 200 micromol x l(-1 ) immediately after exercise . However , muscle soreness , and markers of both muscle damage ( creatine kinase and aspartate aminotransferase ) and lipid peroxidation ( malondialdehyde ) were elevated to an equal extent after exercise in placebo and supplemented trials . Therefore acute supplementation with vitamin C had no beneficial effects although it is possible that such short-term vitamin C supplementation was ineffective because it occurred at an inappropriate time BACKGROUND It was recently reported that antioxidant supplementation decreases training efficiency and prevents cellular adaptations to chronic exercise . OBJECTIVE This study aim ed to investigate the effects of vitamin C and vitamin E supplementation on muscle performance , blood and muscle redox status biomarkers , and hemolysis in trained and untrained men after acute and chronic exercise . A specific type of exercise was applied ( eccentric ) to produce long-lasting and extensive changes in redox status biomarkers and to examine more easily the potential effects of antioxidant supplementation . DESIGN In a double-blinded fashion , men received either a daily oral supplement of vitamin C and vitamin E ( n = 14 ) or placebo ( n = 14 ) for 11 wk ( started 4 wk before the pretraining exercise testing and continued until the posttraining exercise testing ) . After baseline testing , the subjects performed an eccentric exercise session 2 times/wk for 4 wk . Before and after the chronic eccentric exercise , the subjects underwent one session of acute eccentric exercise , physiologic measurements were performed , and blood sample s and muscle biopsy sample s ( from 4 men ) were collected . RESULTS The results failed to support any effect of antioxidant supplementation . Eccentric exercise similarly modified muscle damage and performance , blood redox status biomarkers , and hemolysis in both the supplemented and nonsupplemented groups . This occurred despite the fact that eccentric exercise induced marked changes in muscle damage and performance and in redox status after exercise . CONCLUSION The complete lack of any effect on the physiologic and biochemical outcome measures used raises questions about the validity of using oral antioxidant supplementation as a redox modulator of muscle and redox status in healthy humans The aim of the present study was to investigate whether 2 weeks of vitamin C supplementation affects recovery from an unaccustomed bout of exercise . Sixteen male subjects were allocated to either a placebo ( P ; n = 8) or vitamin C group ( VC ; n = 8) . The VC group consumed 200 mg of ascorbic acid twice a day , whereas the P group consumed identical capsules containing 200 mg of lactose . Subjects performed a prolonged ( 90-min ) intermittent shuttle-running test 14 days after supplementation began . Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation . However , vitamin C supplementation had modest beneficial effects on muscle soreness , muscle function , and plasma concentrations of malondialdehyde . Furthermore , although plasma interleukin-6 increased immediately after exercise in both groups , values in the VC group were lower than in the P group 2 hours after exercise ( p < .05 ) . These results suggest that prolonged vitamin C supplementation has some modest beneficial effects on recovery from unaccustomed exercise |
11,107 | 31,201,527 | Study results indicate that children and adolescents with social anxiety disorder or high social anxiety show emotion dysregulation across all five domains of emotion regulation , such as enhanced social avoidance , more safety behaviors , repetitive negative thinking , biased attention and interpretation of social information , and reduced emotional expression .
While enhanced social avoidance seems to be specific to childhood social anxiety , other maladaptive emotion regulation strategies , such as repetitive negative thinking , seem to occur transdiagnostically across different childhood anxiety disorders . | While numerous studies suggest that emotion dysregulation is important in maintaining social anxiety among adults , the role of emotion regulation in children and adolescents with social anxiety is not yet well understood .
In this systematic review , we use the process model of emotion regulation as a framework for underst and ing emotion regulation in children and adolescents with social anxiety . | Abstract Background Anxiety disorders are among the most common mental health problems in youth , and faulty interpretation bias has been positively linked to anxiety severity , even within anxiety-disordered youth . Quick , reliable assessment of interpretation bias may be useful in identifying youth with certain types of anxiety or assessing changes on cognitive bias during intervention . Objective This study examined the factor structure , reliability , and validity of the Self-report of Ambiguous Social Situations for Youth ( SASSY ) scale , a self-report measure developed to assess interpretation bias in youth . Methods Participants ( N = 488 , age 7–17 ) met diagnostic criteria for social phobia , generalized anxiety disorder , and /or separation anxiety disorder . An exploratory factor analysis was performed on baseline data from youth participating in a large r and omized clinical trial . Results Exploratory factor analysis yielded two factors ( accusation/blame , social rejection ) . The SASSY full scale and social rejection factor demonstrated adequate internal consistency , convergent validity with social anxiety , and discriminant validity as evidence d by non-significant correlations with measures of non-social anxiety . Further , the SASSY social rejection factor accurately distinguished children and adolescents with social phobia from those with other anxiety disorders , supporting its criterion validity , and revealed sensitivity to changes with treatment . Given the relevance to youth with social phobia , pre- and post-intervention data were examined for youth social phobia to test sensitivity to treatment effects ; results suggested that SASSY scores reduced for treatment responders . Conclusions Findings suggest the potential utility of the SASSY social rejection factor as a quick , reliable , and efficient way of assessing interpretation bias in anxious youth , particularly as related to social concerns , in research and clinical setting s. Clinical Trials.gov Number NCT00052078 OBJECTIVE To examine the psychometric properties of a newly developed clinician rating scale , the Liebowitz Social Anxiety Scale for Children and Adolescents ( LSAS-CA ) . METHOD A total of 154 children and adolescents participated in an assessment consisting of a diagnostic interview , the LSAS-CA , and other measures of psychopathology and impairment . Sixty-one of these children also participated in a second LSAS-CA administration , by a different rater blind to diagnosis , within 7 days of the initial assessment . RESULTS High internal consistency ( alpha = .90-.97 for full sample and .83-.95 for social phobia group ) and test-retest reliability ( intraclass correlation coefficient = 0.89 - 0.94 ) were obtained for LSAS-CA total and subscale scores . LSAS-CA scores had stronger associations with measures of social anxiety and general impairment than with a measure of depression . Subjects with social anxiety disorder had significantly higher LSAS-CA scores than subjects with other anxiety disorders and healthy controls . A LSAS-CA cutoff score of 22.5 represented the best balance of sensitivity and specificity when distinguishing between individuals with social phobia and normal controls , whereas a cutoff of 29.5 was optimal for distinguishing social phobia from other anxiety disorders . CONCLUSION Initial findings suggest that the LSAS-CA is a reliable and valid instrument for the assessment of social anxiety disorder This study tested the specificity of the relationship between social anxiety disorder ( SAD ) and coping drinking motives ( versus enhancement drinking motives and social drinking motives ) within the context of a range of potentially confounding variables measured during adolescence ( e.g. , quantity and frequency of alcohol use , coping drinking motives ) and substantively important variables assessed during young adulthood ( e.g. , other anxiety disorders and major depressive disorder ) . A sample of high school sophomores and juniors ( n=717 ) completed measures of substance use and risk factors during adolescence and were then prospect ively followed-up in early- and middle-young adulthood , and psychiatric diagnoses and drinking motives ( i.e. , coping , enhancement , and social ) were assessed each time . Findings indicated that SAD was specifically related to coping motives ( measured during early-to-middle young adulthood ) after controlling for the effects of a range of alcohol and mental health variables . In addition , adolescent variables predicted young adult drinking motives as did major depressive disorder and other anxiety disorders . These findings are discussed within a conceptual framework of the functional role ( e.g. , self-medication ) that drinking motives , and especially coping drinking motives , may play in the etiology of alcohol problems and disorders . Implication s for prevention and treatment interventions are discussed ABSTRACT The purpose of the present study was to see if 7–10-year-old socially anxious children ( n = 26 ) made systematic errors in identifying and sending emotions in facial expressions , para language , and postures as compared with the more r and om errors of children who were inattentive – hyperactive ( n = 21 ) . It was found that socially anxious children made more errors in identifying anger and fear in children 's facial expressions and anger in adults ’ postures and in expressing anger in their own facial expressions than did their inattentive – hyperactive peers . Results suggest that there may be systematic difficulties specifically in visual nonverbal emotion communication that contribute to the personal and social difficulties socially anxious children experience The authors experimentally examined the effects of anger suppression on pain perception . On the basis of ironic process theory , they proposed that efforts to suppress experiential or expressive components of anger may paradoxically enhance cognitive accessibility of anger-related thoughts and feelings , thereby contaminating perception of succeeding pain in an anger-congruent manner . Participants were r and omly assigned to nonsuppression or experiential or expressive suppression conditions during mental arithmetic with or without harassment . A cold-pressor task followed . Results revealed that participants instructed to suppress experiential or expressive components of emotion during harassment not only reported the greatest pain levels , but also rated the anger-specific dimensions of pain uniquely strong . Results suggest that attempts to suppress anger may amplify pain sensitivity by ironically augmenting perception of the irritating and frustrating qualities of pain In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies OBJECTIVE Behavioral inhibition in children has been hypothesized to be a risk factor for the later development of social phobia . However , this hypothesis has yet to be demonstrated in a prospect i ve study . The purpose of the study presented here is to test whether behavioral inhibition in childhood constitutes a risk factor for social phobia during adolescence . METHOD The sample consisted of 2,242 high school students assessed over a 4-year period . Assessment s included self-report question naires , structured clinical interviews , and measurements of heart rate . Cox proportional hazards models were used to evaluate risk . RESULTS Social avoidance , a component of behavioral inhibition , predicted onset of social phobia during high school . However , social avoidance was not related to depression in adolescence . Another component of behavioral inhibition , fearfulness , increased the risk for both social phobia and depression . Among subjects who were both socially avoidant and fearful , 22.3 % developed social phobia -- a risk more than four times greater than that for subjects with neither feature of behavioral inhibition . CONCLUSION This prospect i ve study demonstrates that behavioral inhibition in childhood increases the risk of social phobia in adolescence |
11,108 | 20,091,517 | The results of non-r and omised studies have concluded that a low-phenylalanine diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcomes . | BACKGROUND Phenylketonuria is an inherited disease treated with dietary restriction of the amino acid phenylalanine .
The diet is initiated in the neonatal period to prevent mental h and icap ; however , it is restrictive and can be difficult to follow .
Whether the diet can be relaxed or discontinued during adolescence or should be continued for life remains a controversial issue , which we aim to address in this review .
OBJECTIVES To assess the effects of a low-phenylalanine diet commenced early in life for people with phenylketonuria .
To assess the possible effects of relaxation or termination of the diet on intelligence , neuropsychological outcomes and mortality , growth , nutritional status , eating behaviour and quality of life . | Summary Background Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids ( LCPUFA ) has been related to visual and cognitive development in healthy children in several studies . Children with phenylketonuria ( PKU ) consume diets with very low contents of preformed LCPUFA . We studied prospect ively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life . Subjects and methods Infants with PKU were enrolled at diagnosis ( < 4 weeks of age ) and r and omized double blind to phenylalanine-free amino acid supplements without LCPUFA ( n=11 ) or with both arachidonic ( AA , 0.46 wt% ) and docosahexaenoic acids ( DHA , 0.27 wt% ) ( n=10 ) . At enrolment and again at 1 , 2 , 3 , 4 , 6 , 9 and 12 months , plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocol s. Results Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants . In contrast , supplemented infants had stable and higher LCPUFA levels than unsupplemented infants , reaching significant differences for AA values at 3 , 4 and 6 months , and for DHA values at 1 , 3 , 4 , 6 , 9 and 12 months . Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA . Conclusion Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life . Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes . LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants Cognitive and behavioral effects of temporarily challenging the CNS with elevated levels of phenylalanine in treated phenylketonuria ( PKU ) were investigated in a triple-blind , cross-over study . A high phenylalanine supplement was given over 3 months to sixteen 10- to 16-year-old early and continuously treated children with classical PKU . We used the WISC and Rivermead tests to measure cognitive function and the Rutter Scales to assess disordered behavior . Parents and children guessed at the condition imposed . The Group x Phase interaction for phenylalanine level was statistically significant , but this pattern was not mirrored in the psychological test data , and guessing was r and om . Results suggest that intellectual ability , memory , and conduct are not affected by medium-term hyperphenylalaninaemia in PKU after 10 or more years of treatment Mean of median phenylalanine intakes of 1- to 6-yr-old treated phenylketonuria patients who were growing normally were evaluated by age , sex , and treatment group assignment . Total daily means of median phenylalanine intakes of subjects in treatment group 1 were significantly different from those of subjects in treatment group 2 except at the median age of 69 months . Total daily phenylalanine intakes varied from 285 + /- 10 to 453 + /- 30 mg ( mean + /- SEM ) by subjects in treatment group 1 . Total daily phenylalanine intakes of subjects in treatment group 2 varied from 349 + /- 12 to 530 + /- 42 mg ( mean + /- SEM ) . Mean , median phenylalanine intakes by males ranged from 30 mg/kg of body weight by the younger to 23 mg/kg of body weight by the older subjects . Means of median phenylalanine intakes of females varied from 32 mg/kg of body weight by the younger to 21 mg/kg of body weight by the older subjects . No child had a median phenylalanine intake below 10 mg/kg of body weight OBJECTIVE To determine the effects of large neutral amino acid ( LNAA ) supplements on brain and plasma phenylalanine ( Phe ) levels and other metabolites in early treated subjects with classical phenylketonuria ( PKU ) , and to investigate the relationship between these metabolites and neuropsychological performance . METHODS This was a prospect i ve , double blind , cross over study consisting of four two-week phases with a 4 week washout period . Sixteen subjects ( 7 males ) , with classical PKU were recruited into the study and completed all 4 phases . Each phase consisted of either the LNAA supplement or placebo , and either the patient 's usual medical product or not . Subjects were instructed to follow their usual Phe restricted diet , maintain energy intake and complete a 3-day food record during each phase . At the end of each phase , brain Phe and other metabolites were measured by proton magnetic resonance spectroscopy ( MRS ) , and plasma amino acids quantified . A detailed neuropsychological assessment was performed on the same day as the MRS and plasma collection . RESULTS There was no correlation between plasma and brain Phe , but few of the plasma Phe readings were over 1200 micromol/L. Plasma Phe decreased with LNAA supplementation when patients were not taking their medical formula . LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and cognitive flexibility . Measures of attention were better on medical product , with or without LNAA supplements . CONCLUSIONS LNAA supplementation was associated with a trend to a lowering of plasma Phe levels . LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and flexibility . For individuals already complying with diet and PKU medical product , additional supplementation with LNAA is of limited value . LNAA supplementation may be of benefit to those unable to comply with PKU medical product by reducing plasma Phe , perhaps by competing with Phe at the level of transport across the gut Intelligence and achievement test scores were evaluated for 95 12-year-old children with phenylketonuria who had begun dietary therapy during the neonatal period . Dietary control of blood phenylalanine below 900 mumol/L was maintained beyond age 10 years in 23 children ; 72 others had blood phenylalanine persistently above that level at ages ranging from 18 months to 10 years . Test scores at age 12 years were negatively correlated with the age at initiation of diet and with blood phenylalanine levels from ages 4 to 10 years , and positively correlated with parent IQ scores and the age at loss of dietary control . Children who maintained phenylalanine levels below 900 mumol/L beyond age 10 years showed no deficits in test scores , except for arithmetic , the scores of which declined between ages 6 and 12 years in 90 % of the children in this study . These data strongly support a recommendation that dietary restriction of phenylalanine should be maintained through adolescence Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function . Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction , controversy exists regarding the effects of increased concentrations of phenylalanine in older patients . We have studied ten older , treated , phenylketonuric patients using a triple-blind , multiple trials , crossover design . Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes . Tests included a repeatable battery of neuropsychological tests , analysis of plasma amino acids , and measurement of urine amino acids , phenyl organic acids , dopamine , and serotonin . In all 10 patients plasma phenylalanine rose ( 900 - 4,000 microM ) . In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion . When blood phenylalanine was elevated , these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function . Urinary serotonin fell during phenylalanine loading in six patients . The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient , neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell . We interpret these data as follows : blood phenylalanine above 1.3 mM impairs performance on neuropsychological tests of higher integrative function , this effect is reversible , and one mechanism may involve impaired biogenic amine synthesis Aim : To evaluate the effects of phenylalanine (Phe)‐free essential amino acid ( AA ) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria ( PKU ) . Methods : Phe‐free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospect i ve double‐blinded crossover study . The adaptive behaviour of the patients was tested prior to the study and at 6 and 12 mo after the start , using a simplified version of the Vinel and Adaptive Behaviour Scale . For each sub‐domain , the patients were rated either “ 0 ” ( for poor performance ) or “ 1 ” ( for good performance ) . Neurological signs and symptoms and specific behavioural characteristics were recorded monthly by caretakers . Every 6 mo , neurological examination of the patients was performed , and the caretakers were interviewed . The statistical significance of the results was tested by means of the Fisher 's exact and Wilcoxon tests . Results : The most significant changes were an improved concentration and the development of a meaningful smile , which were observed in 44 % and 43 % of the patients on AA tablet treatment , respectively , but not patients on placebo . Other important but less significant changes included increased awareness of external stimuli ( 63 % ) and less self‐injury ( 43 % ) , and 40 % were smiling and laughing occasionally . The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment ( p=0.002 ) , and to 7.0 in patients when on placebo ( p=0.068 ) . The difference between active AA treatment and placebo was statistically significant ( p=0.027 ) Blood phenylalanine concentrations were experimentally increased for 3 months by means of a phenylalanine-complemented amino acid supplement in a group of 16 children aged 10 - 16 years with classical phenylketonuria who had been treated early and who had remained on the restricted diet . Average concentrations achieved during challenge were between 1000 and 1300 µmol/L. Psychological outcome was measured by a neuropsychological battery consisting of tests of verbal and spatial memory , attention and fine motor coordination . A triple-blind , repeated measures , r and omized , crossover design was adopted to control for practice and expectancy effects . Subjects were assessed at baseline and at the end of the first and second phenylalanine manipulation periods . Significant interactions ( ANOVA ) emerged as predicted for phenylalanine concentrations , but similar crossover effects were not found for any of the neuropsychological tests . The results suggested that medium-term hyperphenylalaninaemia in treated PKU is not harmful to psychological functioning in older children and adolescents who have been continuously treated up to and beyond age 10 years , though the susceptibility of executive functions needs to be further research ed . The findings add some weight to the idea that by late childhood the vulnerability of the nervous system to the neurotoxic influence of phenylalanine may be much reduced Nine adolescents with phenylketonuria ( PKU ) , who had been on unrestricted diets for 2 to 11 years , underwent serial neuropsychological testing over two consecutive 4- to 5-week periods during which each was maintained on a low-phe diet supplemented in a triple-blind fashion either with L-phe ( high phe ) or L-alanine ( low phe ) . Assignment to the initial condition was done r and omly , and the alternate condition was substituted at the end of the first 4- to 5-week period . In 6 of 7 subjects with PKU , baseline median choice reaction times ( RTs ) were slower than those of controls matched for age , sex , h and edness , and Full-Scale IQ ( WISC-R ) . A highly significant improvement occurred during the low-phe phases of the study . Results suggest that adolescents with PKU on unrestricted diets have a neuropsychological deficit that is out of proportion to their overall intellectual h and icap . Moreover , this deficit appears to be at least partly reversible by return to dietary phe restriction despite years of hyperphenylalaninemia ABSTRACT . In a group of 9 patients with classical phenylketonuria ( PKU ) aged 15–24 years we examined the effect of phenylalanine restricted diet on vigilance , as judged by the continuous visual reaction times , and neurotransmitter synthesis , as judged by cerebrospinal fluid ( CSF ) homovanillic acid ( HVA ) and 5‐hydroxyindole acetic acid ( 5‐HIAA ) levels . HVA and 5‐HIAA levels decreased significantly with increase in plasma phenylalanine concentration on free diet ( p<0.01 and p<0.0005 respectively ) . Vigilance improved on phenylalanine restricted diet in 6 of the 7 patients with abnormally long reaction times on free diet . Addition of tyrosine ( 160 mg/kg/24 h ) to the free diet result ed in an increased HVA/5‐HIAA ratio in CSF in the six patients examined . In 14 patients on free diet supplemented with tyrosine , an improvement in vigilance ( reaction times at the 90 percentile ) was seen in all 12 patients with values longer than the normal mean ( 264 msec ) ( p<0.001 ) . Tyrosine treatment may be a therapeutical alternative when phenylalanine restriction is impractical OBJECTIVE To test the efficacy of tyrosine supplementation , as an adjunct to dietary treatment , on neuropsychological test performance in individuals with phenylketonuria . DESIGN A r and omised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases . SETTING The Hospital for Sick Children , Toronto . PARTICIPANTS 21 individuals with phenylketonuria ( ages 6 to 28 years , mean 11.3 ) . INTERVENTION Participants were given 100 mg/kg body weight/d of l-tyrosine or l-alanine ( placebo ) . RESULTS At baseline , performance on several of the neuropsychological test measures was correlated with tyrosine levels . Dietary supplements of tyrosine increased plasma tyrosine concentrations ; however , no change in test performance was found across the tyrosine and placebo phases of the study . CONCLUSIONS Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria OBJECTIVES To characterize abnormalities of brain function in patients with phenylketonuria ( PKU ) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine ( Tyr ) supplementation has a beneficial effect . DESIGN Comparison with a control group ; double-blind , placebo-controlled study comprising six test times ; crossover treatment groups ; oral high-dose Tyr therapy ( 100 mg/kg body weight per day ) or placebo administration for 4 weeks . SUBJECTS Twenty-four early-treated patients with PKU aged 20.8 ( 16 to 25 ) years ; 24 control subjects . METHODS Plasma concentrations of phenylalanine and Tyr were monitored . Neuropsychologic tasks , visual evoked potentials , and spectral analysis of electroencephalographic activity were used to evaluate brain function . RESULTS When patients with PKU were compared with control subjects , deficits in certain aspects of brain function were confirmed ( i.e. , a decreased ability to sustain attention , prolonged latencies of visual evoked potential peaks N1 and P2 , and a reduced amount of fast-wave activity on the electroencephalogram ) . Baseline plasma phenylalanine and Tyr concentrations were in the typical range of adult patients with PKU . The plasma Tyr concentration increased approximately 200 % during Tyr supplementation , but no beneficial effects were observed . CONCLUSIONS High-dose Tyr supplementation can not be recommended as an " alternative " treatment for patients with PKU after relaxation or termination of strict dietary adherence BACKGROUND Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation . We aim ed to test the efficacy of sapropterin , a synthetic form of tetrahydrobiopterin ( BH4 ) , for reduction of blood phenylalanine concentration . METHODS We enrolled 89 patients with phenylketonuria in a Phase III , multicentre , r and omised , double-blind , placebo-controlled trial . We r and omly assigned 42 patients to receive oral doses of sapropterin ( 10 mg/kg ) and 47 patients to receive placebo , once daily for 6 weeks . The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks . Analysis was on an intention-to-treat basis . The study is registered with Clinical Trials.gov , number NCT00104247 . FINDINGS 88 of 89 enrolled patients received at least one dose of study drug , and 87 attended the week 6 visit . Mean age was 20 ( SD 9.7 ) years . At baseline , mean concentration of phenylalanine in blood was 843 ( 300 ) micromol/L in patients assigned to receive sapropterin , and 888 ( 323 ) micromol/L in controls . After 6 weeks of treatment , patients given sapropterin had a decrease in mean blood phenylalanine of 236 ( 257 ) micromol/L , compared with a 3 ( 240 ) micromol/L increase in the placebo group ( p<0.0001 ) . After 6 weeks , 18/41 ( 44 % ) patients ( 95 % CI 28 - 60 ) in the sapropterin group and 4/47 ( 9 % ) controls ( 95 % CI 2 - 20 ) had a reduction in blood phenylalanine concentration of 30 % or greater from baseline . Blood phenylalanine concentrations fell by about 200 micromol/L after 1 week in the sapropterin group and this reduction persisted for the remaining 5 weeks of the study ( p<0.0001 ) . 11/47 ( 23 % ) patients in the sapropterin group and 8/41 ( 20 % ) in the placebo group experienced adverse events that might have been drug-related ( p=0.80 ) . Upper respiratory tract infections were the most common disorder . INTERPRETATION In some patients with phenylketonuria who are responsive to BH4 , sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylalanine diet , and might even replace the diet in some instances Objective : The long-chain polyunsaturated fatty acids ( LC-PUFA ) status of children with PKU is often compromised . LC-PUFA , which are important fatty acids in the development of the CNS , can be synthesis ed endogenously from the parent essential fatty acids ( EFA ) provided dietary intakes are adequate . This study was design ed to assess the biochemical effect over a 20-week period of a phe-free protein substitute that has been supplemented with a balanced blend of n-3 and n-6 EFAs on LC-PUFA status of children with PKU . Design , setting and subjects : Fifty three community-living children aged 1–10 years diagnosed with PKU in the newborn period were recruited from seven tertiary centres in the UK and France and r and omised to a fat-free control formula or the EFA-supplemented test-treatment formula in an open , prospect i ve study . Forty four children completed the study ( 20 controls , 24 test-treatments ) . Fatty acid status was assessed at entry and 20-weeks follow-up . Three day dietary diaries were recorded at 20 weeks ' follow-up . The safety , efficacy and palatability of the test-treatment formula were also assessed . Results : The test-treatment group had significantly higher intakes of fat and EFA than the control group . There was a significant between group difference ( P=0.04 ) in increases in median docosahexaenoic acid ( DHA ) concentrations in erythrocyte phospholipids , which increased by 19 % in the test-treatment group and by 0.5 % in the control group over the study period . Growth and phe control were satisfactory in all subjects . Conclusions : Supplementing the diets of children with PKU with a balanced blend of n-6 and n-3 EFA improves DHA status without compromising AA status The Collaborative Study of children treated for phenylketonuria ( PKUCS ) was conducted to investigate prospect ively the effects of dietary restriction of phenylalanine on the growth and development of these children . Patients with classic phenylketonuria were identified by newborn screening and began treatment shortly thereafter . All were given the restricted diet until age 6 years , when half were r and omly assigned to continue and half to discontinue dietary therapy . By age 10 years , 35 % had deviated from r and omization . The effects of diagnostic , treatment , and psychosocial factors on cognitive test scores were evaluated through 12 years of age . After controlling for parent IQ , significant correlations were noted between various measures of control of blood phenylalanine and their scores on intelligence , reading , spelling and behavior tests , but not for arithmetic or language scores . Bender Gestalt test scores were related to phenylalanine level at the time of testing , but not to early treatment history . These findings strongly support the importance of early initiation of dietary treatment and continuation of therapy throughout childhood During 1967–1983 , the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria ( PKU ) . Subsequently , financial support was provided by the National Institute of Child Health and Human Development ( NICHD ) . The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then r and omized either to continue the diet or to discontinue dietary treatment altogether . One hundred and twenty-five of the 211 children were then followed until 10 years of age . In 1998 , NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical , nutritional , psychological , and socioeconomic status . Fourteen of the original clinics ( 1967–1983 ) participated in the Follow-up Study effort . Each clinic director was provided with a list of PKU subjects who had completed the original study ( 1967–1983 ) , and was asked to evaluate as many as possible using a uniform protocol and data collection forms . In a subset of cases , magnetic resonance imaging and spectroscopy ( MRI/MRS ) were performed to study brain Phe concentrations . The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers , who had an increased rate of eczema , asthma , mental disorders , headache , hyperactivity and hypoactivity . Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations . Abnormal MRI results were associated with higher brain Phe concentrations . Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability , but also in achievement test scores and increased rates of medical and behavioural problems The effects of short-term and long-term phenylalanine ( Phe ) levels on sustained attention have been investigated in phenylketonuria ( PKU ) patients . Two studies , one cross-sectional with 103 patients aged 8.5–9.0 years , the other with 15 adult patients following an interventional design with experimentally manipulated concurrent Phe levels are reported . The effects of concurrent Phe levels separated from long-term Phe control on sustained attention and calculation speed in simple addition tasks were investigated . Children with low concurrent Phe levels performed significantly better than children with high concurrent Phe levels when long-term dietary control was good but not when long-term control was poor . Adult PKU patients with high concurrent Phe levels showed significantly longer reaction times and lower speed in calculation than a healthy control group . Deficits were partly reversible by lowering the concurrent Phe level over a period of 4–5 weeks . The results demonstrated the impact of concurrent Phe level on neuropsychological functioning in childhood as well as in adulthood The age for discontinuing dietary treatment of phenylketonuria ( PKU ) has been a worldwide source of controversy for many years . It is the reason we report here the results of a prospect i ve , controlled study in which the diet was relaxed at 5 years of age in 31 so far well-treated children with classical PKU . The increase of phenylalanine ( Phe ) plasma levels to about 1500 µmol/1 ( 25 mg/dl ) after relaxing the diet was not associated with any significant decline of intellectual performance as measured by the Wechsler scores . Paired comparisons at 7–8 years and 11–13 years of age ( n=12 ) have shown WISC scores of 102.6±16.2 and 104.8±16 , respectively , which were not significantly different . Similarly , paired comparisons at 9–10 years and 14–16 years ( n=6 ) did not demonstrate a significant loss of IQ points ( 107.7±13 vs 104.8±18 ) . Of course , it is possible to argue that we should have observed an increase in IQ with increasing age in our patients and that the absence of deterioration can not be considered by itself as a good result . Nevertheless , it can not be excluded that the subtle but global intellectual impairments that have been documented in early-treated subjects are , to a very substantial degree , determined in the pre-school years , long before there is any question of stopping or relaxing the diet This study demonstrates the feasibility of a r and omized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria . The parents of 14 of 16 children gave informed consent , knowing their children would be r and omly assigned to either a diet-continuation or a diet-termination group . Compared with the continuation group , the mean serum phenylalanine of the termination group was 15.1 mg per dl higher ( P less than 0.005 ) one year , and 9.2 mg per dl higher ( P less than 0.025 ) two years after diet termination . Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group ( P less than 0.01 ) . There were no significant differences in mean head circumferences , height or performances on psychologic tests . At age six , mean I.Q. in the terminated group was 99.8 , in those continuing the diet 103.6 . Children in both groups showed some subtest scatter in memory and concentration . Thus , no harmful effects of diet termination were noted , but a longer period of observation in a larger number of subjects is needed The effect of concurrent phenylalanine levels ( Phe-level ) on sustained attention was tested in a group of 19 early treated adult PKU patients . Mean age was 20.5 years ; WAIS IQs were in the normal range ( M = 109.3 ) . Phe-levels were manipulated in a high-low-high design by re introduction of a strict phenylalanine-reduced diet for 4 to 5 weeks between test time 1 and 2 and returning to usual diet between test time 2 and 3 . A control group of 20 healthy subjects , mean age 20.7 years was tested twice . Results of a sustained attention task are presented . In adult PKU patients with high concurrent Phe-levels , sustained attention is significantly impaired and reaction times are prolonged . In the low Phe-level condition , performance improved significantly . Nevertheless , the PKU group did not reach the level of performance of the control group . Results are not influenced by IQ and suggest a sustained attention deficit in adult PKU patients that varies according to the concurrent Phe-level . The partial reversibility of the deficits provides support for the hypothesis that biochemical mechanisms rather than structural changes of the brain underlie the relationship between concurrent Phe-level and sustained attention This study evaluated the psychiatric characteristics and the behavioral effects of an acute load of phenylalanine on phenylketonuric children . The sample consisted of 13 normal-IQ children who were identified at birth as having phenylketonuria and were subsequently treated with a strict low phenylalanine diet . After baseline measurements , the subjects were loaded with placebo or phenylalanine following a double-blind design . Behavioral and metabolic variables were monitored at hourly intervals for five subsequent hours . The effects of acute loading were measured by changes in a st and ardized Continuous Performance Task ( CPT ) . Psychiatric symptoms were compiled through a structured psychiatric interview of the child and the parent . Results demonstrated that phenylalanine loading , compared to placebo , caused a nonsignificant decrement in performance on CPT testing . Psychiatric disorders were found in six of the 13 subjects with three currently meeting criteria for attention deficit disorder ( ADD ) . In addition , six other subjects were diagnosed in the past as having ADD using DSM-III criteria A collaborative study of diet discontinuation in children with PKU was initiated in 1973 . Children treated with the phenylalanine-restricted diet since early infancy were r and omly assigned to continue or discontinue dietary therapy at age 6 years after parental consent was obtained . The 115 children participating in this study range in age from 8 to 13 years . At 6 years of age , the IQ of continuers and discontinuers was 101 and 97 , respectively . At 8 years , WISC Full-Scale IQ scores adjusted for mean differences on the 6-year Stanford-Binet IQ were 101 for continuers and 98 for discontinuers ( P = 0.075 ) . School performance measured by the Wide Range Achievement Test showed significant differences on reading ( 3.9 vs 3.2 ) and spelling ( 3.3 vs 2.9 ) grade placement , although scores were above actual grade placement ( 2.7 vs 2.6 ) for both groups . Continuers and discontinuers were not different in arithmetic scores , with performance at grade placement of 2.7 and 2.6 respectively . Although these data are preliminary in nature , they suggest that subtle changes in cerebral function may occur in children with PKU in whom the phenylalanine diet has been discontinued The Collaborative Study of Children Treated for Phenylketonuria was initiated in 1967 . The data presented are based on findings in 132 children treated from near birth to 6 years of age . Two treatment groups were r and omly formed . The target for blood phenylalanine was 1.0 to 5.4 mg/100 ml for group 1 and 5.5 to 9.9 mg/100 ml for group 2 . Although mean blood phenylalanine levels for both groups initially fell within the prescribed ranges , a steady increase over time result ed in mean six year levels of 11.4 mg/100 ml and 13.0 mg/100 ml for the two groups , respectively . Because it was not possible to maintain the prescribed differences in blood phenylalanine levels between the two groups , they were combined for further analyses . The mean IQ of the total sample at age 6 years was 98 on the Stanford-Binet Intelligence Scale . Multiple regression analysis showed that , among selected treatment and psychosocial factors , the most important predictors of IQ for 6-year-old children were : ( 1 ) mothers ' intellectual ability ( as measured on the Wechsler Adult Intelligence Scale ) ; ( 2 ) age at which the subjects were first treated ; and ( 3 ) how well the subjects adhered to the phenylalanine-restricted diet . It was concluded that optimal early treatment will result in normal levels of intelligence at 6 years of age |
11,109 | 25,157,064 | INTERPRETATION Baseline cognitive impairment was associated with a significantly higher risk of future stroke , especially ischemic and fatal stroke | BACKGROUND Several studies have assessed the link between cognitive impairment and risk of future stroke , but results have been inconsistent .
We conducted a systematic review and meta- analysis of cohort studies to determine the association between cognitive impairment and risk of future stroke . | Background and Purpose — Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures . We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease ( AD ) risk . Methods — A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring ( age , > 55 years ; mean , 65.7±7.0 ) between 1999 and 2004 ; participants were also free of other neurological conditions that could affect cognition and > 90 % also had brain MRI examination . We related cognitive and MRI measures to risks of incident stroke and AD ⩽10 years of follow-up . As a secondary analysis , we explored these associations in The Framingham Heart Study original cohort ( mean age , 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination , respectively ) . Results — A total of 55 Offspring participants sustained strokes and 31 developed AD . Offspring who scored < 1.5 SD below predicted mean scores , for age and education , on an executive function test , had a higher risk of future stroke ( hazard ratio [ HR ] , 2.27 ; 95 % confidence interval [ CI ] , 1.06–4.85 ) and AD ( HR , 3.60 ; 95 % CI , 1.52–8.52 ) ; additional cognitive tests also predicted AD . Participants with low ( < 20 percentile ) total brain volume and high ( > 20 percentile ) white matter hyperintensity volume had a higher risk of stroke ( HR , 1.97 ; 95 % CI , 1.03–3.77 and HR , 2.74 ; 95 % CI , 1.51–5.00 , respectively ) but not AD . Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts ( HR , 4.41 ; 95 % CI , 2.00–9.72 and HR , 2.37 ; 95 % CI , 1.12–5.00 , respectively ) . A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers . Conclusions — Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction BACKGROUND Analyses of some r and omised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected . We aim ed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk . METHODS The Anglo-Sc and inavian Cardiac Outcomes Trial Blood Pressure Lowering Arm ( ASCOT-BPLA ) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council ( MRC ) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65 - 74 years . We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as st and ard deviation ( SD ) and as transformations uncorrelated with mean blood pressure . For ASCOT-BPLA , we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring ( ABPM ) . RESULTS In ASCOT-BPLA , group systolic blood pressure ( SBP ) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits ( p<0.0001 ) , mainly because of lower within-individual visit-to-visit variability . Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group ( all p<0.0001 ) . Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group . The lower risk of stroke in the amlodipine group ( hazard ratio 0.78 , 95 % CI 0.67 - 0.90 ) was partly attenuated by adjusting for mean SBP during follow-up ( 0.84 , 0.72 - 0.98 ) , but was abolished by also adjusting for within-individual SD of clinic SBP ( 0.99 , 0.85 - 1.16 ) . Findings were similar for coronary events . In the ABPM sub study , reduced variability in daytime SBP in the amlodipine group ( p<0.0001 ) partly accounted for the reduced risk of vascular events , but reduced visit-to-visit variability in clinic SBP had a greater effect . In the MRC trial , group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up ( all p<0.0001 ) . Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk . INTERPRETATION The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure . To prevent stroke most effectively , blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability ; ideally they should reduce both Background and Purpose — The association between stroke and subsequent dementia or Alzheimer disease is well established . What is less understood is the extent to which this association is dependent on prestroke cognitive functioning . The study estimated the occurrence in poststroke dementia as a function of prestroke cognitive status and incident stroke . Methods — Study data were derived from the English Longitudinal Study of Ageing , a 10-year long prospect i ve cohort study of older adults living in Engl and . Baseline data ( 2002/2003 ) were used to group participants into tertiles of cognitive , memory , and executive functioning before an incident stroke . Data from 4 follow-up surveys were used to identify new stroke and poststroke dementia events . Results — The analyses were based on 10 809 participants aged ≥50 years at baseline . High prestroke executive functioning was associated with lower relative risk ( RR ) of dementia ( RR , 0.24 ; 95 % confidence interval , 0.13–0.45 ; P<0.001 ) . Stroke was associated with increased RR of poststroke dementia ( RR , 2.63 ; 95 % confidence interval , 1.80–3.84 ; P<0.001 ) . The association of stroke with poststroke dementia was greater for participants with higher prestroke executive functioning ( interaction term RR , 4.4 ; 95 % confidence interval , 1.35–14.63 ; P=0.014 ) . For participants with higher executive functioning , the probability of dementia was 0.3 % without stroke and 3.1 % after stroke , compared with 1.9 % and 5.2 % for lower executive functioning . Conclusions — Stroke and prestroke cognition were independently associated with increased probability of poststroke dementia . Stroke results in disproportionate increase in the risk of dementia when premorbid cognitive functioning is high BACKGROUND Silent brain infa rcts are frequently seen on magnetic resonance imaging ( MRI ) in healthy elderly people and may be associated with dementia and cognitive decline . METHODS We studied the association between silent brain infa rcts and the risk of dementia and cognitive decline in 1015 participants of the prospect i ve , population -based Rotterdam Scan Study , who were 60 to 90 years of age and free of dementia and stroke at base line . Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period . We performed Cox proportional-hazards and multiple linear-regression analyses , adjusted for age , sex , and level of education and for the presence or absence of subcortical atrophy and white-matter lesions . RESULTS During 3697 person-years of follow-up ( mean per person , 3.6 years ) , dementia developed in 30 of the 1015 participants . The presence of silent brain infa rcts at base line more than doubled the risk of dementia ( hazard ratio , 2.26 ; 95 percent confidence interval , 1.09 to 4.70 ) . The presence of silent brain infa rcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function . Silent thalamic infa rcts were associated with a decline in memory performance , and nonthalamic infa rcts with a decline in psychomotor speed . When participants with silent brain infa rcts at base line were subdivided into those with and those without additional infa rcts at follow-up , the decline in cognitive function was restricted to those with additional silent infa rcts . CONCLUSIONS Elderly people with silent brain infa rcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions OBJECTIVES To investigate the effect of cognitive impairment on fatal and nonfatal incident stroke in older adults . DESIGN A large , national , prospect i ve , population -based study of a representative cohort of older Canadians followed over a 10-year period . SETTING Secondary analyses were conducted using data from the Canadian Study of Health and Aging , a population -based study of older adults followed prospect ively from 1991 to 2001 . PARTICIPANTS Nine thous and four hundred fifty-one adults aged 65 and older who had not previously been diagnosed with stroke at baseline ( in 1991 ) . MEASUREMENTS In addition to known risk factors , the independent contribution of cognitive function ( diagnosed in a clinical examination ) was examined as a risk for stroke in older adults . RESULTS Multinomial logistic regression analyses showed that cognitive impairment was associated with twice the odds of fatal incident stroke , controlling for well-established risk factors . CONCLUSION This study provides further evidence for the need to consider cognitive function in relation to stroke risk in older population OBJECTIVE Recent studies have suggested that vascular dementia in older persons is more common than previously hypothesized . A substantial proportion of dementia in old age may be an early manifestation of cerebrovascular disease ( CVD ) , that eventually becomes clinical ly evident as an acute cerebrovascular accident . This study was aim ed at assessing whether cognitive impairment and cognitive decline in older persons free of stroke are associated with higher risk of future stroke , independently of other risk factors . DESIGN Population -based prospect i ve study . PARTICIPANTS A total of 5024 subjects from the Established Population s for Epidemiologic Studies of the Elderly , who were alive and had no history of previous stroke at the sixth follow-up visit . Subjects who had reported a stroke in a previous interview or with a diagnosis of cerebrovascular disease in a hospitalization record during the previous 3 years were excluded . MEASUREMENTS Cognitive function was assessed by the Short Portable Mental Status Question naire ( SPMSQ ) . Occurrence of a stroke was prospect ively assessed by examining hospital discharge diagnoses and death certificates . RESULTS During 19,533 person-years of follow-up , 259 strokes were recorded ( 13.3/1000 person-years ) . Stroke incidence was lowest in those with normal SPMSQ score ( 12.1/1000 person-years ) , intermediate in those with moderate impairment ( 16.3/1000 person-years ) , and highest in those with severe impairment ( 30.9/1000 person-years ) . Adjusting for age , education , smoking , history of hypertension , blood pressure , heart attack , diabetes , and disability , the relative risks of stroke for moderate and severe cognitive impairment were 1.2 ( 0.9 - 1.6 ) and 2.2 ( 1.2 - 3.8 ) , respectively . The association between cognitive impairment and incident stroke was not mediated by hypertension or diabetes . Compared with subjects with stable or improved SPMSQ score in the previous 3 years , those who declined had higher risk of stroke . CONCLUSIONS The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play larger role in causing cognitive impairment then previously suspected . It remains to be demonstrated whether reducing modifiable risk factors for CVD decreases the burden of cognitive impairment in older persons without stroke Background and Purpose — Several studies indicate that stroke increases the risk of dementia . Most of these studies lacked the ability to take accurately assessed prestroke cognitive function into account . Whether the effects of stroke merely unravel an ongoing underlying dementing process or in fact cause the dementia has implication s for the prevention of dementia in persons with cerebrovascular disease . We explored in a prospect i ve cohort study whether stroke occurrence was related to a higher risk of subsequent dementia and whether this association was dependent on prestroke slope of cognitive function . Methods — Cox proportional hazard models were used to relate incident stroke as a time-varying exposure with the risk of dementia in 6724 participants of the Rotterdam Study without dementia or stroke at baseline ( 49 361 person years of follow-up ) . Subsequently Cox proportional hazard models were performed to assess whether this association was dependent on slope of prestroke cognitive performance and other risk factors for cognitive decline . Results — Independent of both level and the rate of change of prestroke cognitive performance and other risk factors for cognitive decline , incident stroke was associated with a more than doubled risk of subsequent dementia ( hazard ratio , 2.1 ; 95 % CI , 1.55 to 2.81 ) . Conclusions — Prestroke cognitive function is not a major determinant of the effect of stroke on the risk of poststroke dementia Objective : We aim ed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy ( CAA ) . Methods : We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B ( PiB ) . Mean distribution volume ratio ( DVR ) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at “ simulated ” hemorrhages , r and omly placed in the same subjects using a probability distribution map of CAA-hemorrhage location . Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds . Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained . Results : Nine of 11 subjects had at least one new microbleed on follow-up MRI ( median 4 , interquartile range [ IQR ] 1–9 ) and 2 had 5 new intracerebral hemorrhages . Mean DVR was greater at the sites of incident bleeds ( 1.34 , 95 % confidence interval [ CI ] 1.23–1.46 ) than simulated lesions ( 1.14 , 95 % CI 1.07–1.22 , p < 0.0001 ) in multivariable models . PiB retention decreased with increasing distance from sites of observed bleeds ( p < 0.0001 ) . Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates ( p = 0.003 ) . Conclusions : Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA Cerebral small vessel disease ( SVD ) , including white matter lesions ( WML ) and lacunar infa rcts , is related to objective cognitive impairment but also to subjective cognitive failures ( SCF ) . SCF have reported to be an early predictor of dementia . Cerebral microbleeds ( MB ) are another manifestation of SVD and have been related to cognitive impairment , but the role of MB in SCF has never been studied . We therefore investigated whether MB are related to SCF among non-demented elderly individuals with SVD , independent of coexisting WML and lacunar infa rcts . The RUN DMC study is a prospect i ve cohort study among 503 older persons with cerebral SVD between 50 and 85 years of age . All participants underwent FLAIR and T2 * scanning . SCF , subjective memory failures ( SMF ) , and subjective executive failures ( SEF ) were assessed . The relation between SCF and the presence , number and location of MB was assessed by linear regression analyses adjusted for age , sex , education , depressive symptoms , cognitive function , total brain volume , normalized hippocampal volume , territorial infa rcts , WML , and lacunar infa rcts . MB were present in 11 % . We found a relation between the presence , total number and lobar located MB , and SCF , SMF , and SEF and the reported progression of these failures , especially in participants with good objective cognitive function . In conclusion , MB are related to SCF independent of co-existing WML and lacunar infa rcts , especially in those with good objective cognitive performance . These results suggest that MB are associated with the earliest manifestations of cognitive impairment . MB may help us to underst and the role of the ever-exp and ing spectrum of SVD in cognitive impairment Previous reports suggest that brain white matter changes , a surrogate for small vessel disease , are related to cerebral amyloid angiopathy ( CAA ) . However , this relationship has not been explored in population -based studies or in the oldest old ( > 85 years of age ) . We studied the relationships between white matter hyperintensities ( WMH ) determined by post-mortem magnetic resonance imaging ( MRI ) and neuropathologically assessed CAA in demented and nondemented subjects enrolled in the prospect i ve community-based Finnish Vantaa 85 + Study . In this analysis , we evaluated scans and brain sample s from 123 subjects ( 86 % women ) with a mean age of 90.6 years . We found CAA to be present in 63 % of the 123 subjects , whereas WMH was present in 74 % , and dementia in 59 % . The presence of WMH of any severity did not relate to the presence or the degree of CAA severity , irrespective of the dementia status of the subjects . Furthermore , multivariate regression analysis showed a clear association between CAA and dementia but WMH was not related to dementia in this very old sample . We conclude that severe WMH may not be determined by CAA in this very elderly population Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age ( > 70 years ) . Design Prospect i ve cohort study . Setting PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) study , a collaboration between centres in Irel and , Scotl and , and the Netherl and s. Participants 5461 participants , mean age 75.3 years , who were at risk of cardiovascular disease . Blood pressure was measured every three months during an average of 3.2 years . Visit-to-visit variability in blood pressure was defined as the st and ard deviation of blood pressure measurements between visits . Main outcome measures Four domains of cognitive function , testing selective attention , processing speed , and immediate and delayed memory . In a magnetic resonance imaging sub study of 553 participants , structural brain volumes , cerebral microbleeds , infa rcts , and white matter hyperintensities were measured . Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests : attention ( mean difference high versus low thirds ) 3.08 seconds ( 95 % confidence interval 0.85 to 5.31 ) , processing speed −1.16 digits coded ( 95 % confidence interval −1.69 to −0.63 ) , immediate memory −0.27 pictures remembered ( 95 % confidence interval −0.41 to −0.13 ) , and delayed memory −0.30 pictures remembered ( 95 % confidence interval −0.49 to −0.11 ) . Furthermore , higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infa rcts , and higher variability in diastolic blood pressure was associated with cerebral microbleeds ( all P<0.05 ) . All associations were adjusted for average blood pressure and cardiovascular risk factors . Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age Abstract Objectives : To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over . Design : A 20 year follow up study of a cohort of r and omly selected elderly people living in the community who in 1973 - 4 had taken part in a nutritional survey funded by the Department of Health and Social Security . Setting : Eight areas in Britain ( five in Engl and , two in Scotl and , and one in Wales ) . Subjects : 921 men and women whose cognitive function was assessed by a geriatrician in 1973 - 4 and for whom data on health , socioeconomic circumstances , and diet had been recorded . Results : Cognitive impairment was associated with increased mortality , in particular death from ischaemic stroke . Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 ( 95 % confidence interval 1.4 to 5.5 ) , compared with those who gained the maximum score ( 10 ) , after adjustment for age , sex , blood pressure , serum cholesterol concentration , and vitamin C intake . These associations were independent of illness or social class . At the time of the nutritional survey , cognitive function was poorest in those with the lowest vitamin C status , whether measured by dietary intake or plasma ascorbic acid concentration . The relation between vitamin C status and cognitive function was independent of age , illness , social class , or other dietary variables . Conclusion : The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function . Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis . A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease . Key messages Key messages In this prospect i ve study of 921 elderly people cognitive impairment was a strong predictor of death from ischaemic stroke Low vitamin C intake and low plasma ascorbate concentrations were also important risk factors for death from stroke Cognitive performance was poorest in people with the lowest vitamin C status A high vitamin C intake may protect against both cognitive impairment and cerebrovascular Objective : To determine whether carotid endarterectomy is superior to best medical therapy in preserving cognition , and whether low Mini-Mental State Examination ( MMSE ) scores predict TIA , stroke , myocardial infa rct ion , or death . Methods : Subjects participating in the Asymptomatic Carotid Atherosclerosis Study were administered the MMSE at periodic intervals . Group means were calculated at r and omization , 1 and 3 months later , and every 6 months thereafter . The group means were compared by treatment and over time . A proportional hazard regression model incorporating postr and omization MMSE score as a predictor variable was used to estimate risk of death , stroke , or other outcome events . Results : There was no intergroup difference in mean MMSE score during 5 years of observation . For individual patients , the relationship between a low postr and omization score on the MMSE and increased risk of death was significant ( p ≤ 0.0001 ) . Patients who experienced stroke after r and omization also had a significant and persistent reduction in MMSE score ( p ≤ 0.0001 ) . Conclusions : Carotid endarterectomy had no impact on MMSE score in this study . Patients with low postr and omization MMSE scores had a greater likelihood of death . Stroke reduced MMSE scores and may portend cognitive impairment . The authors recommend the routine inclusion of cognitive testing in future clinical trials design ed to evaluate prophylaxis or acute therapy of stroke BACKGROUND Given the high prevalence of cognitive impairment in older Mexican Americans and limited longitudinal research examining cognitive function in this ethnic group , we conducted a study examining whether cognitive impairment is a risk factor for new onset of stroke among older Mexican Americans . METHODS We performed a prospect i ve cohort study of 2682 Mexican Americans aged 65 years and older living in the southwestern United States . For subjects with no prior history of stroke and who completed the Mini-Mental State Examination ( MMSE ) at baseline , stroke incidence was assessed after 2 , 5 , and 7 years of follow-up . RESULTS In Cox proportional regression models , MMSE score at baseline predicted risk of incident stroke over a 7-year follow-up period . For the unadjusted model , subjects with an MMSE score of 21 or higher were half as likely to report stroke at follow-up ( hazard ratio [ HR ] , 0.49 ; 95 % confidence interval [ CI ] , 0.35 - 0.69 ; p < .001 ) compared with those with a score of less than 21 . We found similar results after controlling for relevant risk factors for stroke including age , gender , smoking status , education , body mass index , diabetes , heart attack , systolic blood pressure , and depressive symptoms ( HR , 0.54 ; 95 % CI , 0.38 - 0.77 ; p = .001 ) . Additionally , each 1-point increase in MMSE score was associated with a 5 % reduction in risk ( HR , 0.95 ; 95 % CI , 0.92 - 0.99 ; p = .01 ) . CONCLUSIONS Increasing MMSE score is associated with a decreasing incidence of stroke in older Mexican Americans . This study highlights the need for a more aggressive focus on identifying and addressing cognitive decline in the Mexican American population |
11,110 | 29,214,975 | NHS and carer support costs were variable but , overall , were lower in the intervention arm than the TAU arm .
Our multicomponent health promotion intervention was acceptable and delivered at modest cost .
Our small study shows promise for improving clinical outcomes , including functioning and independence . | BACKGROUND Mild frailty or pre-frailty is common and yet is potentially reversible .
Preventing progression to worsening frailty may benefit individuals and lower health/social care costs .
However , we know little about effective approaches to preventing frailty progression .
OBJECTIVES ( 1 ) To develop an evidence - and theory-based home-based health promotion intervention for older people with mild frailty .
( 2 ) To assess feasibility , costs and acceptability of ( i ) the intervention and ( ii ) a full-scale clinical effectiveness and cost-effectiveness r and omised controlled trial ( RCT ) . | Objective To assess whether an intervention based on nurse home visits including alert buttons ( NV+AB ) is effective in reducing frailty compared to nurse home visits alone ( NV-only ) and usual care ( control group ) for older adults . Design Unblinded , r and omized , controlled trial . Setting Insured population covered by the Mexican Social Security Institute living in the city of Ensenada , Baja California , Mexico . Participants Patients were aged over 60 years with a frailty index score higher than 0.14 . Intervention After screening and informed consent , participants were allocated r and omly to the control , NV+AB , or NV-only groups . Measurements The primary outcome was the frailty score 9 months later . Quality of life , depression , comorbidities , health status , and health service utilization were also considered . Results The framing sample included 819 patients . Of those , 591 were not located because they did not have a l and line/telephone ( 341 patients ) , they had died ( 107 ) , they were ill ( 50 ) , or they were not currently living in the city ( 28 ) . A screening interview was applied to 228 participants , and 57 had a score ≤0.14 , 171 had ≥0.14 , and 16 refused to complete the baseline question naire . A home visit was scheduled for 155 patients . However , 22 did not complete the baseline question naire . The final 133 subjects were r and omized into the NV+AB ( n = 45 ) , NV-only ( n = 44 ) , and control ( n = 44 ) groups . There were no statistically significant differences in the baseline characteristics of the groups . The mean age overall was 76.3 years ( st and ard deviation 4.7 ) and 45 % were men . At the baseline , 61.65 % were classified as frail . At end of follow-up the adjusted prevalence of frailty in NV+AB group was 23.3 % versus 58.3 % in the control group . Conclusion : An intervention based on NV+AB seems to have a positive effect on frailty scores Abstract A new version of the EQ‐5D , the EQ‐5D‐5L , is available . The aim of this study is to produce a value set to support use of EQ‐5D‐5L data in decision‐making . The study design followed an international research protocol . R and omly selected members of the English general public completed 10 time trade‐off and 7 discrete choice experiment tasks in face‐to‐face interviews . A 20‐parameter hybrid model was used to combine time trade‐off and discrete choice experiment data to generate values for the 3,125 EQ‐5D‐5L health states . Valuation data are available for 996 respondents . Face validity of the data has been demonstrated , with more severe health states generally given lower values . Problems with pain/discomfort and anxiety/depression received the greatest weight . Compared to the existing EQ‐5D‐3L value set , there are considerably fewer “ worse than dead ” states ( 5.1 % , compared with over one third ) , and the minimum value is higher . Values range from −0.285 ( extreme problems on all dimensions ) to 0.950 ( for health states 11211 and 21111 ) . Results have important implication s for users of the EQ‐5D‐5L both in Engl and and internationally . Quality ‐adjusted life year gains from interventions seeking to improve very poor health may be smaller using this value set and may previously have been overestimated OBJECTIVES : To evaluate the effectiveness of a home visiting program on health-related measures in a population of older people with poor health status . DESIGN : R and omized , clinical trial . SETTING : Community-dwelling citizens in the Netherl and s. PARTICIPANTS : Three hundred thirty people aged 70 to 84 r and omly assigned to an intervention group ( n=160 ) or a control group ( n=170 ) . INTERVENTION : Eight home visits , lasting 1 hour or more , with telephone follow-up , over an 18-month period , conducted by experienced home nurses under supervision of a public health nurse ; key elements of the ( systematic ) visits were assessment of health problems and risks , advice , and referral to professional and community services . MEASUREMENTS : Self-rated health , functional status , quality of life , and changes in self-reported problems . RESULTS : No differences were found between the intervention and control group in these and other outcome measures at the end of the intervention Background Falls in older people are a major public health issue , but the underlying causes are complex . We sought to evaluate the effectiveness of preventive home visits as a multifactorial , individualized strategy to reduce falls in community-dwelling older people . Methods Data were derived from a prospect i ve r and omized controlled trial with follow-up examination after 18 months . Two hundred and thirty participants ( ≥80 years of age ) with functional impairment were r and omized to intervention and control groups . The intervention group received up to three preventive home visits including risk assessment , home counseling intervention , and a booster session . The control group received no preventive home visits . Structured interviews at baseline and follow-up provided information concerning falls in both study groups . R and om-effects Poisson regression evaluated the effect of preventive home visits on the number of falls controlling for covariates . Results R and om-effects Poisson regression showed a significant increase in the number of falls between baseline and follow-up in the control group ( incidence rate ratio 1.96 ) and a significant decrease in the intervention group ( incidence rate ratio 0.63 ) controlling for age , sex , family status , level of care , and impairment in activities of daily living . Conclusion Our results indicate that a preventive home visiting program can be effective in reducing falls in community-dwelling older people In this article we explore older people ’s perspectives on the benefits of preventive home visits ( PHVs ) , after long-term follow-up . PHVs are health services intended to promote older people ’s health and independence , prevent disease , and postpone functional decline . We applied an explorative and descriptive design and analyzed qualitative research interviews of 10 PHV users who had received multiple visits for at least 6 years . We sought manifest and latent content in our analysis . The participants reported benefits falling within four main categories : to feel safe , to manage everyday life , to live well , and to be somebody . Two latent themes emerged : living with an underlying , realistic concern about an uncertain future , and striving to maintain oneself as a person . The perceived benefits of PHVs differed significantly from the outcome measures commonly used in r and omized , controlled trials . PHV interventions should have a longitudinal approach and support each person ’s current needs and valued goals BACKGROUND Multimorbidity is associated with higher mortality , increased disability , a decline in functional status and a lower quality of life . The objective of the study is to explore patterns of multimorbidity in an elderly population . METHODS 328 community inhabitants aged 85 years were included . Socio-demographic variables and data from the global geriatric assessment were evaluated . Information on the presence of sixteen common chronic conditions was collected : hypertension , diabetes mellitus , dyslipidemia , ischemic cardiomyopathy , heart failure , stroke , chronic obstructive pulmonary disease , ( COPD ) , atrial fibrillation , peripheral arterial disease , Parkinson 's disease , cancer , dementia , anemia , chronic kidney disease ( CKD ) , visual impairment and deafness . Hierarchical cluster analysis was performed . RESULTS The rate of multimorbidity ( > 1 disease ) was 95.1 % . Men had a higher percentage of COPD and malignancy . Four main clusters were identified . The highest value of the bivariate correlation matrix was that between heart failure and visual impairment . These two diseases were included in a cluster with atrial fibrillation , CKD , heart failure , stroke , high blood pressure and diabetes mellitus . CONCLUSIONS The large majority of oldest old subjects had multimorbidity . The results confirm the non-r and om co-occurrence of certain diseases in this age group Background evidence on the effectiveness of interventions to prevent frailty is scarce . Objective to assess the effect of an intervention in preventing frailty progression in pre-frail older people . Study design a r and omised , open label , controlled trial with two parallel arms . Population community-dwelling pre-frail older people ( ≥70 years ) consulting in primary care . Intervention nutritional assessment ( and derivation to a Nutritional Unit for usual care in the event of nutritional risk ) and a physical activity programme including aerobic exercise and a set of mixed strengthening , balance and coordination exercises . Control group patients receiving the usual care . Main outcome measure prevalence of frailty ( Fried criteria ) at 12 months . Secondary outcomes measures functional capacity ( Barthel index ) , falls and nutritional status ( Short-Form Mini Nutritional Assessment ) on follow-up at 12 months . Results one hundred and seventy-two participants were recruited and r and omised ( mean age : 78.3 years ; mean number of Fried criteria : 1.45 ) . Thirty-nine participants ( 22.6 % ) were dropped out during the study . At follow-up , 4.9 % of the intervention group and 15.3 % of the control group had evolved to frailty , for a crude odds ratio ( OR ) of 0.29 ( 95 % confidence interval [ CI ] : 0.08 - 1.08 ; P = 0.052 ) and an adjusted ( by age , gender and number of co-morbidities ) OR of 0.19 ( 95 % CI : 0.04 - 0.95 ; P = 0.044 ) . Intervention group showed a higher outdoors walking hour per day ( 0.97 versus 0.73 ; P = 0.019 ) but no difference was observed in muscle strength , gait speed or other functional indicators . Conclusion an intervention focused on physical exercise and maintaining good nutritional status may be effective in preventing frailty in community-dwelling pre-frail older individuals . Clinical Trials.gov identifier NCT02138968 Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information Background An ageing population , a growing prevalence of chronic diseases and limited financial re sources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly . A wide variety of measures is generally available for the prevention of falls and fall-related injuries . The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors . However , the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear . Against this background , the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention . Research questions The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries . The target population are the elderly ( > 60 years ) , living in their own housing or in long term care facilities . Further research questions refer to the cost-effectiveness of fall prevention measures , and their ethical , social and legal implication s. Methods Systematic literature search es were performed in 31 data bases covering the publication period from January 2003 to January 2010 . While the effectiveness of interventions is solely assessed on the basis of r and omised controlled trials ( RCT ) , the assessment of the effectiveness of diagnostic procedures also considers prospect i ve accuracy studies . In order to clarify social , ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration , irrespective of their study design . Study selection and critical appraisal were conducted by two independent assessors . Due to clinical heterogeneity of the studies no meta-analyses were performed . Results Out of 12,000 references retrieved by literature search es , 184 meet the inclusion criteria . However , to a variable degree the validity of their results must be rated as compromised due to different biasing factors . In summary , it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinical ly relevant information . Positive effects of exercise interventions may be expected in relatively young and healthy seniors , while studies indicate opposite effects in the fragile elderly . For this specific vulnerable population the modification of the housing environment shows protective effects . A low number of studies , low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet : correction of vision disorders , modification of psychotropic medication , vitamin D supplementation , nutritional supplements , psychological interventions , education of nursing personnel , multiple and multifactorial programs as well as the application of hip protectors . For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature search es yield very few useful results . Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems . Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention . The willingness to take up preventive measures depends on a variety of personal factors , the quality of information , guidance and decision-making , the prevention program itself and social support . The analysis of papers regarding legal issues shows three main challenges : the uncertainty of which st and ard of care has to be expected with regard to fall prevention , the necessity to consider the specific conditions of every single case when measures for fall prevention are applied , and the difficulty to balance the rights to autonomous decision making and physical integrity . Discussion and conclusions The assessment of clinical effectiveness of interventions for fall prevention is complicated by inherent method ological problems ( esp . absence of blinding ) and meaningful clinical heterogeneity of available studies . Therefore meta-analyses are not appropriate , and single study results are difficult to interpret . Both problems also impair the informative value of economic analyses . With this background it has to be stated that current recommendations regarding fall prevention in the elderly are not fully supported by scientific evidence . In particular , for the generation of new recommendations the dependency of probable effects on specific characteristics of the target population s or care setting s should be taken into consideration . This also applies to the variable factors influencing the willingness of the target population to take up and pursue preventive measures . In the planning of future studies equal weight should be placed on method ological rigour ( freedom from biases ) and transferability of results into routine care . Economic analyses require input of German data , either in form of a “ piggy back study “ or in form of a modelling study that reflects the structures of the German health care system and is based on German epidemiological and cost data OBJECTIVE To investigate methods to determine the size of a pilot study to inform a power calculation for a r and omized controlled trial ( RCT ) using an interval/ratio outcome measure . STUDY DESIGN Calculations based on confidence intervals ( CIs ) for the sample st and ard deviation ( SD ) . RESULTS Based on CIs for the sample SD , methods are demonstrated whereby ( 1 ) the observed SD can be adjusted to secure the desired level of statistical power in the main study with a specified level of confidence ; ( 2 ) the sample for the main study , if calculated using the observed SD , can be adjusted , again to obtain the desired level of statistical power in the main study ; ( 3 ) the power of the main study can be calculated for the situation in which the SD in the pilot study proves to be an underestimate of the true SD ; and ( 4 ) an " efficient " pilot size can be determined to minimize the combined size of the pilot and main RCT . CONCLUSION Trialists should calculate the appropriate size of a pilot study , just as they should the size of the main RCT , taking into account the twin needs to demonstrate efficiency in terms of recruitment and to produce precise estimates of treatment effect Background Meeting the needs of the growing number of older people is a challenge for health and social care services . Home-based interventions aim ing to modify health-related behaviours of frail older people have the potential to improve functioning and well-being . Previous review s have focused on whether such interventions are effective , rather than what might make them effective . Recent advances in behavioural science make possible the identification of potential ‘ active ingredients ’ of effective interventions , such as component behaviour change techniques ( BCTs ) , and intended intervention functions ( IFs ; e.g. to educate , to impart skills ) . This paper reports a protocol for a systematic review that seeks to ( a ) identify health behaviour change interventions for older frail people , ( b ) describe the content of these interventions , and ( c ) explore links between intervention content and effectiveness . The protocol is reported in accordance with Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s ( PRISMA -P ) 2015 guidelines . Methods / design Studies will be identified through a systematic search of 15 electronic data bases , supplemented by citation tracking . Studies will be retained for review where they report r and omised controlled trials focusing on home-based health promotion delivered by a health professional for frail older people in community setting s , written in English , and either published from 1980 onwards , or , for registered trials only , unpublished but completed with results obtainable from authors . Interventions will be coded for their content ( BCTs , IFs ) and for evidence of effectiveness ( outcome data relating to behavioural and health outcomes ) . Analyses will describe characteristics of all interventions . Interventions for which effectiveness data are available will be categorised into those showing evidence of effectiveness versus those showing no such evidence . The potential for each intervention characteristic to contribute to change in behaviour or health outcomes will be estimated by calculating the percentage of all interventions featuring those characteristics that have shown effectiveness . Discussion Results will reveal the strategies that have been drawn on within home-based interventions to modify the health behaviours of frail older people , and highlight those more associated with positive changes in behaviour and health . Findings from this review will provide a useful basis for underst and ing , developing , and implementing behaviour change interventions in this field . Systematic review registration PROSPERO Objective To evaluate whether an interdisciplinary primary care approach for community dwelling frail older people is more effective than usual care in reducing disability and preventing ( further ) functional decline . Design Cluster r and omised controlled trial . Setting 12 general practice s in the south of the Netherl and s Participants 346 frail older people ( score ≥5 on Groningen Frailty Indicator ) were included ; 270 ( 78 % ) completed the study . Interventions General practice s were r and omised to the intervention or control group . Practice s in the control group delivered care as usual . Practice s in the intervention group implemented the “ Prevention of Care ” ( PoC ) approach , in which frail older people received a multidimensional assessment and interdisciplinary care based on a tailor made treatment plan and regular evaluation and follow-up . Main outcome measures The primary outcome was disability , assessed at 24 months by means of the Groningen Activity Restriction Scale . Secondary outcomes were depressive symptomatology , social support interactions , fear of falling , and social participation . Outcomes were measured at baseline and at 6 , 12 , and 24 months ’ follow-up . Results 193 older people in the intervention group ( six practice s ) received the PoC approach ; 153 older people in the control group ( six practice s ) received care as usual . Follow-up rates for patients were 91 % ( n=316 ) at six months , 86 % ( n=298 ) at 12 months , and 78 % ( n=270 ) at 24 months . Mixed model multilevel analyses showed no significant differences between the two groups with regard to disability ( primary outcome ) and secondary outcomes . Pre-planned subgroup analyses confirmed these results . Conclusions This study found no evidence for the effectiveness of the PoC approach . The study contributes to the emerging body of evidence that community based care in frail older people is a challenging task . More research in this field is needed . Trial registration Current Controlled Trials IS RCT N31954692 BACKGROUND Little is known about the natural course of frailty . We performed a prospect i ve study to determine the transition rates between frailty states and to evaluate the effect of the preceding frailty state on subsequent frailty transitions . METHODS We studied 754 community-living persons , aged 70 years or older , who were nondisabled in 4 essential activities of daily living . Frailty , assessed every 18 months for 54 months , was defined on the basis of weight loss , exhaustion , low physical activity , muscle weakness , and slow walking speed . Participants were classified as frail if they met 3 or more of these criteria , as prefrail if they met 1 or 2 of the criteria , and as nonfrail if they met none of the criteria . RESULTS Of the 754 participants , 434 ( 57.6 % ) had at least 1 transition between any 2 of the 3 frailty states during 54 months . The rates were 36.8 % , 21.5 % , and 9.2 % for 1 , 2 , and 3 transitions , respectively . During the 18-month intervals , transitions to states of greater frailty were more common ( rates up to 43.3 % ) than transitions to states of lesser frailty ( rates up to 23.0 % ) , and the probability of transitioning from being frail to nonfrail was very low ( rates , 0%-0.9 % ) , even during an extended period . The likelihood of transitioning between frailty states was highly dependent on one 's preceding frailty state . CONCLUSIONS Frailty among older persons is a dynamic process , characterized by frequent transitions between frailty states over time . Our findings suggest ample opportunity for the prevention and remediation of frailty 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 Background Although resistance exercise interventions have been shown to be beneficial in prefrail or frail older adults it remains unclear whether there are residual effects when the training is followed by a period of detraining . The aim of this study was to establish the sustainability of a muscle power or muscle strength training effect in prefrail older adults following training and detraining . Methods 69 prefrail community-dwelling older adults , aged 65–94 years were r and omly assigned into three groups : muscle strength training ( ST ) , muscle power training ( PT ) or controls . The exercise interventions were performed for 60 minutes , twice a week over 12 weeks . Physical function ( Short Physical Performance Battery = SPPB ) , muscle power ( sit-to-st and transfer = STS ) , self-reported function ( SF-LLFDI ) and appendicular lean mass ( aLM ) were measured at baseline and at 12 , 24 and 36 weeks after the start of the intervention . Results For the SPPB , significant intervention effects were found at 12 weeks in both exercise groups ( ST : p = 0.0047 ; PT : p = 0.0043 ) . There were no statistically significant effects at 24 and 36 weeks . In the ST group , the SPPB declined continuously after stop of exercising whereas the PT group and controls remained unchanged . No effects were found for muscle power , SF-LLFDI and aLM . Conclusions The results showed that both intervention types are equally effective at 12 weeks but did not result in statistically significant residual effects when the training is followed by a period of detraining . The unchanged SPPB score at 24 and 36 weeks in the PT group indicates that muscle power training might be more beneficial than muscle strength training . However , more research is needed on the residual effects of both interventions . Taken the drop-out rates ( PT : 33 % , ST : 21 % ) into account , muscle power training should also be used more carefully in prefrail older adults . Trial registration This trial has been registered with clinical trials.gov ( NCT00783159 OBJECTIVE To assess the efficacy of a home care program design ed to improve access to medical care for older adults with multiple chronic conditions who are at risk for hospitalization . STUDY DESIGN R and omized controlled trial in which participants were assigned to the home care intervention ( Choices for Healthy Aging [ CHA ] ) program or usual care . METHODS The intervention group consisted of 298 older adults at risk of hospitalization as determined by a risk stratification tool . Measures included satisfaction with medical care , medical service use , and costs of medical care . RESULTS The intervention group reported significantly greater satisfaction with care than usual care recipients ( t test = 2.476 ; P = .014 ) . CHA patients were less likely than usual care patients to be admitted to the hospital ( 25.6 % and 37.1 % , respectively ; P = .02 ) . There were no differences in terms of costs of care between the home care and usual care groups . CONCLUSIONS Provision of home care to older adults at high risk of hospitalization may improve satisfaction with care while reducing hospitalizations . Lack of difference in medical costs suggests that managed care organizations need to consider targeting rather than using risk stratification measures when design ing programs for high-risk groups The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the principles might also apply . The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct . We followed recommended good practice to develop the extension , including carrying out a Delphi survey , holding a consensus meeting and research team meetings , and piloting the checklist . The aims and objectives of pilot and feasibility r and omised studies differ from those of other r and omised trials . Consequently , although much of the information to be reported in these trials is similar to those in r and omised controlled trials ( RCTs ) assessing effectiveness and efficacy , there are some key differences in the type of information and in the appropriate interpretation of st and ard CONSORT reporting items . We have retained some of the original CONSORT statement items , but most have been adapted , some removed , and new items added . The new items cover how participants were identified and consent obtained ; if applicable , the prespecified criteria used to judge whether or how to proceed with a future definitive RCT ; if relevant , other important unintended consequences ; implication s for progression from pilot to future definitive RCT , including any proposed amendments ; and ethical approval or approval by a research review committee confirmed with a reference number . This article includes the 26 item checklist , a separate checklist for the abstract , a template for a CONSORT flowchart for these studies , and an explanation of the changes made and supporting examples . We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials . Editor ’s note : In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites Background With population ageing , research is needed into new low-cost , scalable methods of effective promotion of health and wellbeing for older people . We aim ed to assess feasibility , reach and costs of implementing a new tailored computer-aided health and social risk appraisal system in primary care . Methods Design : Feasibility study . Setting : Five General Practice s in London ( Ealing ) and Hertfordshire , United Kingdom ( UK ) Participants : R and om sample of patients aged 65 + years . Intervention : The Multi-dimensional Risk Appraisal for Older people ( MRA-O ) system includes : 1 ) Postal question naire including health , lifestyle , social and environmental domains ; 2 ) Software system generating a personalised feedback report with advice on health and wellbeing ; 3 ) Follow-up of people with new concerning or complex needs by GPs or practice nurses . Evaluation : Feasibility of implementation ; participant wellbeing , functional ability and quality of life ; social needs , health risks , potential lifestyle changes ; and costs of implementation . Results Response rates to initial postal invitations were low ( 526/1550 , 34 % ) . Of these , 454/526 ( 86 % ) completed MRA-O assessment s. Compared to local UK Census data on older people , participants were younger , more were owner-occupiers and fewer were from ethnic minority groups than expected . A range of problems was identified by participants , including pain in last week ( 269/438 , 61.4 % ) , low physical activity ( 173/453 , 38.2 % ) , sedentary lifestyle ( 174/447 , 38.3 % ) , falls ( 117/439 , 26.7 % ) , incontinence ( 111/441 25.2 % ) , impaired vision 116/451 ( 25.7 % ) , impaired hearing ( 145/431 , 33.6 % ) , depressed mood ( 71/451 , 15.7 % ) , impaired memory ( 44/444 9.9 % ) , social isolation ( 46/449 , 10.2 % ) and loneliness ( 31/442 , 7.0 % ) . Self-rated health was good/excellent in 312/437 ( 71.4 % ) , and quality of life and well-being were slightly above age-specific population norms . Implementation costs were low . Practice s review ed medical records of 143/454 ( 31.5 % ) of participants as a consequence of their responses , and actively followed up 110/454 ( 24.2 % ) of their patients . Conclusions A computer-aided risk appraisal system was feasible for General Practice s to implement , yields useful information about health and social problems , and identifies individual needs . Participation rates were however low , particularly for the oldest old , the poorest , and ethnic minority groups , and this type of intervention may increase inequalities in access . Widespread implementation of this approach would require work to address potential inequalities OBJECTIVE To examine the impact of a muscle resistance program ( MRP ) on muscular and functional performance and on interleukin 6 ( IL-6 ) and soluble tumor necrosis factor receptor-1 ( sTNFr1 ) plasma levels in prefrail community-dwelling women . DESIGN R and omized controlled trial crossover design with a postintervention and short-term follow-up . SETTING University hospital . PARTICIPANTS Prefrail community-dwelling women ( N=32 ; ≥65y ) . INTERVENTION The MRP was design ed based on the exercise at 75 % of each participant 's maximum load ( 10wk , 3 times/wk ) . MAIN OUTCOME MEASURES Plasma concentrations of IL-6 and sTNFr1 ( high-sensitivity enzyme-linked immunosorbent assay kits ) , muscle strength of the knee extensors ( isokinetic ) , and functional performance ( Timed Up & Go [ TUG ] test and 10-meter walk test [ 10MWT ] ) . RESULTS There were significant differences in functional and muscular performance between the pre-MRP , post-MRP , and 10-week follow-up period . After the MRP , both functional ( TUG , pre-MRP=11.1s vs post-MRP=10.4s , P=.00 ; 10MWT , pre-MRP=4.9s vs post-MRP , 4.4s , P=.00 ) and muscular performances ( pre-MRP=77.8 % and post-MRP=83.1 % , P=.02 ) improved . After cessation of the MRP ( follow-up period ) , sTNFr1 plasma levels increased by 21.4 % at 10-week follow-up ( post-MRP , 406.4pg/mL ; 10-week follow-up , 517.0pg/mL ; P=.03 ) . There were significant differences in sTNFr1 ( P=.01 ) . CONCLUSIONS The MRP was effective in improving functional and muscular performances , although alterations in plasma levels of IL-6 and sTNFr1 could not be identified after the MRP . Cessation of the MRP after 10 weeks result ed in increased plasma levels of sTNFr1 Background : Few studies of the association between prospect i ve falls and sensor-based measures of motor performance and physical activity ( PA ) have evaluated subgroups of frailty status separately . Objective : To evaluate wearable sensor-based measures of gait , balance , and PA that are predictive of future falls in community-dwelling older adults . Methods : The Arizona Frailty Cohort Study in Tucson , Arizona , followed community-dwelling adults aged 65 years and over ( without baseline cognitive deficit , severe movement disorders , or recent stroke ) for falls over 6 months . Baseline measures included Fried frailty criteria : in-home and sensor-based gait ( normal and fast walk ) , balance ( bipedal eyes open and eyes closed ) , and spontaneous daily PA over 48 h , measured using vali date d wearable technologies . Results : Of the 119 participants ( 36 % non-frail , 48 % pre-frail , and 16 % frail ) , 48 reported one or more fall ( 47 % of non-frail , 33 % of pre-frail , and 47 % of frail ) . Although balance deficit and PA were independent fall predictors in pre-frail and frail groups , they were not sensitive to predict prospect i ve falls in the non-frail group . Even though gait performance deteriorated as frailty increased , gait was not a predictor of prospect i ve falls when participants were stratified based on frailty status . In pre-frail and frail participants combined , center of mass sway [ odds ratio ( OR ) = 5.9 , 95 % confidence interval ( CI ) 2.6 - 13.7 ] , PA mean walking bout duration ( OR = 1.1 , 95 % CI 1.0 - 1.2 ) , PA mean st and ing bout duration ( OR = 0.94 , 95 % CI 0.91 - 0.99 ) , and a fall in previous 6 months ( OR = 7.3 , 95 % CI 1.5 - 36.4 ) were independent predictors of prospect i ve falls ( area under the curve : 0.882 ) . Conclusion : This study suggests that independent predictors of falls are dependent on frailty status . Among sensor-derived parameters , balance deficit , longer typical walking episodes , and shorter typical st and ing episodes were the most sensitive predictors of prospect i ve falls in the combined pre-frail and frail sample . Gait deficit was not a sensitive fall predictor in the context of frailty status 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 Pilot studies play an important role in health research , but they can be misused , mistreated and misrepresented . In this paper we focus on pilot studies that are used specifically to plan a r and omized controlled trial ( RCT ) . Citing examples from the literature , we provide a method ological framework in which to work , and discuss reasons why a pilot study might be undertaken . A well-conducted pilot study , giving a clear list of aims and objectives within a formal framework will encourage method ological rigour , ensure that the work is scientifically valid and publishable , and will lead to higher quality RCTs . It will also safeguard against pilot studies being conducted simply because of small numbers of available patients Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems . Amino acid deficiency , including L-carnitine , has been proposed to be associated with its pathophysiology . Nevertheless , the efficacy of L-carnitine supplementation on frailty status has not been documented . Thus , this study aim ed to determine the effect of 10-week L-carnitine supplement ( 1.5 g/day ) on frailty status and its biomarkers and also physical function , cognition , and nutritional status among prefrail older adults in Klang Valley , Malaysia . Methodology This study is a r and omized , double-blind , placebo-controlled clinical trial conducted among 50 prefrail subjects r and omized into two groups ( 26 in L-carnitine group and 24 in placebo group ) . Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit , selected frailty biomarkers ( interleukin-6 , tumor necrosis factor-alpha , and insulin-like growth factor-1 ) , physical function , cognitive function , nutritional status and biochemical profile . Results The results indicated that the mean scores of Frailty Index score and h and grip test were significantly improved in subjects supplemented with L-carnitine ( P<0.05 for both parameters ) as compared to no change in the placebo group . Based on Fried criteria , four subjects ( three from the L-carnitine group and one from the control group ) transited from prefrail status to robust after the intervention . Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults OBJECTIVES The purpose of this study was to examine whether a 12-week combined physical exercise training and nutritional intervention improves physical performance and enhances health-related quality of life ( HRQOL ) among prefrail elderly women living in the community . DESIGN This was a r and omized controlled trial in which participants were recruited and r and omly assigned to the exercise and nutrition group ( EN , n = 30 ) , exercise only group ( E , n = 28 ) , and control group ( C , n = 31 ) . SETTING Group training classes were held at a research center in Itabashi Ward , Tokyo , Japan . PARTICIPANTS Eighty-nine prefrail women aged 70 years or older . INTERVENTION The EN group participated in an exercise training and nutritional program ( cooking class ) once a week , and the E group participated in the exercise training program only . MEASUREMENTS Outcome measures that included physical performance ( h and grip strength , balance , walking speed ) and HRQOL ( Medical Outcomes Study 36-Item Short Form Health Survey ) were obtained at entry , the end of the 12-week intervention , and 6 months after completion of the intervention program . RESULTS At the end of the 12-week intervention , significant improvements in the physical component summary score and 3 ( role physical , bodily pain , role emotional ) of the 8 domains of the Medical Outcomes Study 36-Item Short Form Health Survey were observed in the EN group . The E group exhibited a significantly increased h and grip strength at postintervention . The positive effects , however , were not maintained at 6-month follow-up , but were reduced . CONCLUSIONS The combined physical exercise training and nutritional intervention program has beneficial effects on several domains of HRQOL and h and grip strength in prefrail elderly women living in the community . However , further studies are needed to examine approaches that facilitate maintenance of the improved outcomes by combined exercise training and nutritional intervention ABSTRACT BACKGROUND Patients at risk for generating high health care expenditures often receive fragmented , low- quality , inefficient health care . Guided Care is design ed to provide proactive , coordinated , comprehensive care for such patients . OBJECTIVE We hypothesized that Guided Care , compared to usual care , produces better functional health and quality of care , while reducing the use of expensive health services . DESIGN 32-month , single-blind , matched-pair , cluster-r and omized controlled trial of Guided Care , conducted in eight community-based primary care practice s. PATIENTS The “ Hierarchical Condition Category ” ( HCC ) predictive model was used to identify high-risk older patients who were insured by fee-for-service Medicare , a Medicare Advantage plan or Tricare . Patients with HCC scores in the highest quartile ( at risk for generating high health care expenditures during the coming year ) were eligible to participate . INTERVENTIONA registered nurse collaborated with two to five primary care physicians in providing eight services to participants : comprehensive assessment , evidence -based care planning , proactive monitoring , care coordination , transitional care , coaching for self-management , caregiver support , and access to community-based services . MAIN MEASURES Functional health was measured using the Short Form–36 . Quality of care and health services utilization were measured using the Patient Assessment of Chronic Illness Care and health insurance cl aims , respectively . KEY RESULTS Of the eligible patients , 904 ( 37.8 % ) gave written consent to participate ; of these , 477 ( 52.8 % ) completed the final interview , and 848 ( 93.8 % ) provided complete cl aims data . In intention-to-treat analyses , Guided Care did not significantly improve participants ’ functional health , but it was associated with significantly higher participant ratings of the quality of care ( difference = 0.27 , 95 % CI = 0.08–0.45 ) and 29 % lower use of home care ( 95 % CI = 3–48 % ) . CONCLUSIONS Guided Care improves high-risk older patients ’ ratings of the quality of their care , and it reduces their use of home care , but it does not appear to improve their functional health 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 Background : It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults . Objective : The purpose of the present study was to compare the effects of strength training ( ST ) versus power training ( PT ) on functional performance in prefrail older adults . This study was registered at clinical trials.gov as NCT00783159 . Methods : 69 community-dwelling older adults ( > 65 years ) who were prefrail according to the definition of Fried were included in a 12-week exercise program . The participants were r and omized into an ST group , a PT group and a control group . All participants were supplemented with vitamin D3 orally before entering the intervention period . The primary outcome was the global score on the Short Physical Performance Battery ( SPPB ) . Secondary outcomes were muscle power , appendicular lean mass ( aLM ) measured by dual energy X-ray absorptiometry and self-reported functional deficits ( Short Form of the Late-Life Function and Disability Instrument , SF-LLFDI ) . Results : Regarding changes in the SPPB score during the intervention , significant heterogeneity between the groups was observed ( p = 0.023 ) . In pair-wise comparisons , participants in both training groups significantly ( PT : p = 0.012 , ST : 0.009 ) increased their SPPB score ( PT : Δmean = 0.8 , ST : Δmean = 1.0 ) compared to the control group , with no statistical difference among training groups ( p = 0.301 ) . No statistical differences were found in changes in aLM ( p = 0.769 ) , muscle power ( p = 0.308 ) and SF-LLFDI ( p = 0.623 ) between the groups . Muscle power significantly increased ( p = 0.017 ) under vitamin D3 intake . Conclusions : In prefrail community-dwelling adults , PT is not superior to ST , although both training modes result ed in significant improvements in physical performance . With regard to dropout rates , ST appears to be advantageous compared to PT . The high prevalence of vitamin D3 deficiency and the slight improvement of physical performance under vitamin D3 supplementation among study participants underline the relevance of this approach in physical exercise interventions OBJECTIVE To compare the costs and cost-effectiveness of a multifactorial interdisciplinary intervention versus usual care for older people who are frail . DESIGN Cost-effectiveness study embedded within a r and omized controlled trial . SETTING Community-based intervention in Sydney , Australia . PARTICIPANTS A total of 241 community-dwelling people 70 years or older who met the Cardiovascular Health Study criteria for frailty . INTERVENTION A 12-month multifactorial , interdisciplinary intervention targeting identified frailty characteristics versus usual care . MEASUREMENTS Health and social service use , frailty , and health-related quality of life ( EQ-5D ) were measured over the 12-month intervention period . The difference between the mean cost per person for 12 months in the intervention and control groups ( incremental cost ) and the ratio between incremental cost and effectiveness were calculated . RESULTS A total of 216 participants ( 90 % ) completed the study . The prevalence of frailty was 14.7 % lower in the intervention group compared with the control group at 12 months ( 95 % CI 2.4%-27.0 % ; P = .02 ) . There was no significant between-group difference in EQ-5D utility scores . The cost for 1 extra person to transition out of frailty was $ A15,955 ( at 2011 prices ) . In the " very frail " subgroup ( participants met > 3 Cardiovascular Health Study frailty criteria ) , the intervention was both more effective and less costly than the control . A cost-effectiveness acceptability curve shows that the intervention would be cost-effective with 80 % certainty if decision makers were willing to pay $ A50,000 per extra person transitioning from frailty . In the very frail sub population , this reduced to $ 25,000 . CONCLUSION For frail older people residing in the community , a 12-month multifactorial intervention provided better value for money than usual care , particularly for the very frail , in whom it has a high probability of being cost saving , as well as effective . Trial registration : ACTRN12608000250336 OBJECTIVES To determine whether exercise training added to ongoing hormone replacement therapy ( HRT ) increases bone mineral density ( BMD ) in physically frail elderly women . DESIGN Prospect i ve controlled trial . SETTING University-based research center . PARTICIPANTS Twenty-eight women on HRT , aged 75 and older with physical frailty . INTERVENTIONS Participants were assigned to 9 months of supervised ( EXER ) or home ( HOME ) exercise . The EXER program started with physical therapy and gradually incorporated resistance and endurance training . The HOME program consisted of flexibility exercises . MEASUREMENTS Changes in BMD and body composition . RESULTS There were larger increases in lumbar spine BMD in response to EXER than with HOME ( 3.5 % vs 1.5 % , P = .048 ) , with a trend for larger increases in total body BMD ( 1.5 % vs 0.2 % , P = .058 ) . There were no significant between-group differences in hip BMD . The EXER group had decreases in weight ( -2.2 + /- 0.3 kg , P = .010 ) and fat mass ( -2.7 + /- 0.4 kg , P = .018 ) and increases in muscle strength ( 9 - 30 % , P < .05 ) . CONCLUSION In physically frail elderly women on HRT , relatively vigorous exercise training significantly increased lumbar spine BMD . The improved BMD and strength in response to exercise could reduce fracture risk in frail women already on HRT OBJECTIVES To examine the outcomes of the Elderly Persons in the Risk Zone study , which was design ed to evaluate whether it is possible to delay deterioration if a health-promoting intervention is made when an older adult ( ≥80 ) is at risk of becoming frail and whether a multiprofessional group intervention is more effective in delaying deterioration than a single preventive home visit with regard to frailty , self-rated health , and activities of daily living ( ADLs ) at 3-month follow-up . DESIGN R and omized , three-armed , single-blind , controlled trial performed between November 2007 and May 2011 . SETTING Two urban districts of Gothenburg , Sweden . PARTICIPANTS Four hundred fifty-nine community-living adults aged 80 and older not dependent on the municipal home help service . INTERVENTION A preventive home visit or four weekly multiprofessional senior group meetings with one follow-up home visit . MEASUREMENTS Change in frailty , self-rated health , and ADLs between baseline and 3-month follow-up . RESULTS Both interventions delayed deterioration of self-rated health ( odds ratio ( OR ) = 1.99 , 95 % confidence interval ( CI ) = 1.12 - 3.54 ) . Senior meetings were the most beneficial intervention for postponing dependence in ADLs ( OR = 1.95 , 95 % CI = 1.14 - 3.33 ) . No effect on frailty could be demonstrated . CONCLUSION Health-promoting interventions made when older adults are at risk of becoming frail can delay deterioration in self-rated health and ADLs in the short term . A multiprofessional group intervention such as the senior meetings described seems to have a greater effect on delaying deterioration in ADLs than a single preventive home visit . Further research is needed to examine the outcome in the long term and in different context Cette étude a déterminé les effets et les coûts d'une approche d'équipe multifactoriel et interdisciplinaire à la prévention des chutes . Essai contrôlé aléatoire de 109 adultes plus âgés qui sont à risque de chutes . Ce fut une stratégie de prévention multifactoriel fondée sur des données probantes de 6 mois , impliquant une équipe interdisciplinaire . Le résultat principal a été le nombre des chutes suivi pendant 6 mois . À 6 mois , il n'y a aucune différence dans le nombre moyen de chutes entre groupes . Des analyses des sous-groupes ont montrés que l'intervention réduit efficacement les chutes chez les hommes ( 75 - 84 ans ) qui ont peur de tomber ou une histoire négative de chutes . Le nombre de glissades et de trébuchés a été considérablement réduit , et la santé émotionnelle a montré une amélioration plus importante dans le fonctionnement lié à la santé émotionnelle dans le groupe d'intervention . La qualité de vie a été améliorée , glissades et trébuchés ont été réduits , comme l'étaient les chutes chez les hommes qui avaient peur de tomber ou une histoire de chutes négative . This study determined the effects and costs of a multifactorial , interdisciplinary team approach to falls prevention . R and omized controlled trial of 109 older adults who are at risk for falls . This was a six-month multifactorial and evidence -based prevention strategy involving an interdisciplinary team . The primary outcome was number of falls during the six-month follow-up . At six months , no difference in the mean number of falls between groups . Subgroup analyses showed that the intervention effectively reduced falls in men ( 75 - 84 years old ) with a fear of falling or negative fall history . Number of slips and trips was greatly reduced ; and emotional health had a greater improvement in role functioning related to emotional health in the intervention group . Quality of life was improved , slips and trips were reduced , as were falls among males ( 75 - 84 years old ) with a fear of falling or negative fall history OBJECTIVES Although deficits in skeletal muscle strength , gait , balance , and oxygen uptake are potentially reversible causes of frailty , the efficacy of exercise in reversing frailty in community-dwelling older adults has not been proven . The aim of this study was to determine the effects of intensive exercise training ( ET ) on measures of physical frailty in older community-dwelling men and women . DESIGN R and omized controlled trial . SETTING Medical school research center . PARTICIPANTS One hundred fifteen sedentary men and women ( mean age + /- st and ard deviation = 83 + /- 4 ) with mild to moderate physical frailty , as defined by two of the following three criteria : Modified Physical Performance Test ( modified PPT ) score between 18 and 32 , peak oxygen uptake ( VO2 peak ) between 10 and 18 mL/kg/min , and self-report of difficulty or assistance with one basic activity of daily living ( ADL ) , or two instrumental ADLs . INTERVENTION Participants were r and omly assigned to a control group that performed a 9-month low-intensity home exercise program ( control ) or an exercise-training program ( ET ) . The control intervention primarily consisted of flexibility exercises . ET began with 3 months of flexibility , light-resistance , and balance training . During the next 3 months , resistance training was added , and , during the next 3 months , endurance training was added . MEASUREMENTS Modified PPT score , VO2 peak , performance of ADLs as measured by the Older Americans Re sources and Services instrument , and the Functional Status Question naire ( FSQ ) . RESULTS ET result ed in significantly greater improvements than home exercise in three of the four primary outcome measures . Adjusted 95 % confidence bounds on the magnitude of improvement in the ET group compared with the control group were 1.0 to 5.2 points for the modified PPT score , 0.9 to 3.6 mL/kg/min for VO2 peak , and 1.6 to 4.9 points for the FSQ score . CONCLUSIONS Our results show that intensive ET can improve measures of physical function and pre clinical disability in older adults who have impairments in physical performance and oxygen uptake and are not taking hormone replacement therapy better than a low-intensity home exercise program Purpose : To examine the effectiveness of a novel intervention aim ed at decreasing indices related to frailty through systematic , Progressive Functional Rehabilitation ( PFR ) . Methods : Pre‐frail volunteers were recruited to participate in a 15 week exercise intervention or control group . Those who met study criteria and consented were r and omized into one of three groups : control , seated exercise , or Wii ® ‐fit . Test measures were completed before and after the 15 week intervention period on all participants . Measures included : Senior Fitness Test , Body Weight , Balance Efficacy Scale , CHAMPS , Late‐Life Function and Disability Index , MOS SF‐36 . Attendance was also recorded . Results : There were improvements on several of the measures included in the Senior Fitness Test including chair st and s , arm curls , step 2 , six minute walk , sit and reach , and the timed up and go . A few participants did lose weight . All of the differences reflected improved physical functional status in the seated exercise or Wii‐fit groups compared with the control group . Discussion : Increased physical activity was beneficial for all who participated . There were improvements in physical performance scores on several of the measures on the senior fitness test in both the seated exercise and Wii‐fit groups . Participants in the Wii‐fit group also showed improvement in their reported caloric expenditure and balance confidence . Conclusion : This pilot study suggests a rehabilitation effect that was similar to the effect of community based senior fitness classes . A home video game console system with weight vest could be an effective alternative for pre‐frail senior adults to group exercise classes BACKGROUND The diffusion of comprehensive geriatric assessment services has been rather limited in North America partly because of reimbursement and organizational constraints . OBJECTIVE To evaluate the impact of a comprehensive geriatric assessment intervention for frail older patients that is started before hospital discharge and is continued at home . METHODS Patients older than 65 years were selected who had either unstable medical problems , recent functional limitations , or potentially reversible geriatric clinical problems . Patients ( n = 354 ) were r and omly assigned to either the intervention group or a control group . Information on survival , readmissions , nursing home placement , medication use , and health status was collected at 30 and 60 days after hospital discharge . RESULTS No differences were observed between the two treatment groups in survival , hospital readmission , or nursing home placement by 60 days . After adjustment for baseline characteristics , no significant differences were observed between the two groups on measures of physical functioning , social functioning , role limitations , health perceptions , pain , mental health , energy and /or fatigue , health change , or overall well-being . CONCLUSIONS Although efficacy has been demonstrated for some forms of comprehensive geriatric assessment , the types of services that are easier to establish ( inpatient consultation services and ambulatory assessment ) have not been shown to improve outcomes . Our results indicate that outcomes are unaffected by a limited form of comprehensive geriatric assessment begun in the hospital and completed at home . Further efforts are needed to develop and to evaluate realistic approaches to comprehensive geriatric assessment Background : Self-management of complex medication regimens for chronic illness is challenging for many older adults . Objectives : The purpose of this study was to evaluate health status outcomes of frail older adults receiving a home-based support program that emphasized self-management of medications using both care coordination and technology . Design : This study used a r and omized controlled trial with three arms and longitudinal outcome measurement . Setting : Older adults having difficulty in self-managing medications ( n = 414 ) were recruited at discharge from three Medicare-certified home healthcare agencies in a Midwestern urban area . Methods : All participants received baseline pharmacy screens . The control group received no further intervention . A team of advanced practice nurses and registered nurses coordinated care for 12 months to two intervention groups who also received either an MD.2 medication-dispensing machine or a medplanner . Health status outcomes ( the Geriatric Depression Scale , Mini Mental Status Examination , Physical Performance Test , and SF-36 Physical Component Summary and Mental Component Summary ) were measured at baseline and at 3 , 6 , 9 , and 12 months . Results : After covariate and baseline health status adjustment , time × group interactions for the MD.2 and medplanner groups on health status outcomes were not significant . Time × group interactions were significant for the medplanner and control group comparisons . Discussion : Participants with care coordination had significantly better health status outcomes over time than those in the control group , but addition of the MD.2 machine to nurse care coordination did not result in better health status outcomes OBJECTIVES To assess whether serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations relate to transitions between the states of robustness , prefrailty , and frailty and to mortality in older adults . DESIGN The Invecchiare in Chianti ( InCHIANTI ) Study , a prospect i ve cohort study . SETTING Tuscany , Italy . PARTICIPANTS Adults aged 65 and older ( N = 1,155 ) . MEASUREMENTS Serum 25(OH)D concentrations measured at baseline ; frailty state ( robust , prefrail , frail ) assessed at baseline and 3 and 6 years after enrollment ; and vital status determined 3 and 6 years after enrollment . RESULTS The median ( interquartile range ) 25(OH)D concentration was 16.0 ng/mL ( 10.4 - 25.6 ng/mL ; multiply by 2.496 to convert to nmol/L ) . Prefrail participants with 25(OH)D levels less than 20 ng/mL were 8.9 % ( 95 % confidence interval ( CI ) = 2.5 - 15.2 % ) more likely to die , 3.0 % ( 95 % CI = -5.6 - 14.6 % ) more likely to become frail , and 7.7 % ( 95 % CI = -3.5 - 18.7 % ) less likely to become robust than prefrail participants with 25(OH)D levels of 20 ng/mL or more . In prefrail participants , each 5-ng/mL decrement of continuous 25(OH)D was associated with 1.46 times higher odds of dying ( 95 % CI = 1.18 - 2.07 ) and 1.13 higher odds of incident frailty ( 95 % CI = 0.90 - 1.39 ) than with recovery of robustness . Transitions from robustness or frailty were not associated with 25(OH)D levels . CONCLUSION Results provide evidence that prefrailty is an " at risk " state from which older adults with high 25(OH)D levels are more likely to recover than to decline , but high 25(OH)D levels were not associated with recovery from frailty . Thus , 25(OH)D levels should be investigated as a potential therapy to treat prefrailty and prevent further decline Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases , prompting calls for widespread treatment of individuals with low vitamin D levels . Most of New Zeal and 's population have vitamin D levels for at least part of the year that are considered insufficient ( 25-hydroxyvitamin D < 50 - 80 nmol/L ) . However , evidence for benefits of vitamin D supplementation in such population s is controversial and there is some evidence of harmful effects . Until adequately powered , r and omised , controlled trials of vitamin D supplementation demonstrate safe improvements in health , clinicians should not focus on detecting/treating individuals with vitamin D insufficiency , instead treating those at high risk of vitamin D deficiency ( 25-hydroxyvitamin D < 25 nmol/L ) , such as the frail elderly , and those with specific clinical indications . Treatment for such individuals does not require vitamin D measurements . Requests for vitamin D measurements in Auckl and have nearly quadrupled in the past decade , from 8500 in the year 2000 to 32,800 in 2010 , with substantial increases in cost . Vitamin D measurement is often inaccurate and imprecise , and the vast majority of tests performed currently do not reveal vitamin D deficiency . Therefore , a move away from routine vitamin D measurements seems sensible , though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia AIM This paper reports a study evaluating the comparative effects and costs of a proactive nursing health promotion intervention in addition to usual home care for older people compared with usual home care services alone . BACKGROUND An ageing population , budget constraints and technological advances in many countries have increased the pressure on home care re sources . The result is a shift in nursing services from health promotion to meet the more pressing need for postacute care . For frail older people with long-term needs , these changes combine to create a fragmented system of health service delivery , characterized by providing nursing on dem and rather than proactively . METHODS A two-armed , single-blind , r and omized controlled trial was carried out with older people > or = 75 years and eligible for personal support services through a home care programme in Ontario , Canada . Participants were r and omly allocated either to usual home care ( control ) or to a nursing ( experimental ) group . In addition to usual home care , the nursing group received a health assessment combined with regular home visits or telephone contacts , health education about management of illness , coordination of community services , and use of empowerment strategies to enhance independence . The data were collected in 2001 - 2002 . RESULTS Of the 288 older people who were r and omly allocated at baseline , 242 ( 84 % ) completed the study ( 120 nursing group ; 122 control group ) . Proactively providing older people with nursing health promotion , compared with providing nursing services on-dem and , result ed in better mental health functioning ( P = 0.009 ) , a reduction in depression ( P = 0.009 ) , and enhanced perceptions of social support ( P = 0.009 ) at no additional cost from a societal perspective . CONCLUSIONS Home based nursing health promotion , proactively provided to frail older people with chronic health needs , enhances quality of life while not increasing the overall costs of health care . The results underscore the need to re-invest in nursing services for health promotion for older clients receiving home care 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 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 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 BACKGROUND The aim of this study was to examine the effects on functional and psychosocial parameters and long-term care utilization of a preventive home visit program for ambulatory frail Japanese elders . METHODS Eligible participants ( n = 323 ) were r and omly assigned to intervention ( n = 161 ) or control group ( n = 162 ) . Nurses and care managers provided structured preventive home visits to the intervention group participants every 6 months over 2 years . Activities of daily living ( ADLs ) , instrumental activities of daily living ( IADLs ) , depression , and social support were collected via mail question naire at baseline and at 12- and 24-month follow-up points . The utilization of long-term care insurance was documented over the period . RESULTS Two-way analysis of covariance did not show significant outcome differences overall . In a pre-planned subgroup analysis for participants who had at least one ADL dependency at baseline , those in the intervention group ( N = 105 ) were significantly less likely to deteriorate over 2 years in their function and depression than those in the control group ( N = 100 ) : ADLs ( p = .0311 ) , IADLs ( p = .0114 ) , depression ( p = .0001 ) . The total long-term care costs over 2 years in the intervention group ( 36,001 credits ) were higher than in the control group ( 26,022 credits ) ( nonsignificant ) , and elders in the intervention group utilized significantly more community and institutional long-term care services than those in the control group over the period 7 months to 15 months after the intervention started . CONCLUSIONS The results suggest that a preventive home visit program might be ineffective on functional and psychosocial status among ambulatory frail elders overall , although it might significantly improve ADLs , IADLs and depression for those with ADL dependency |
11,111 | 29,053,651 | Obesity is characterized by a chronic sub clinical inflammation that could exacerbate other chronic inflammatory disorders like as periodontitis .
CONCLUSIONS The association between obesity and periodontitis was consistent with a compelling pattern of increased risk of periodontitis in overweight or obese individuals .
Although the underlying pathophysiological mechanism remains unclear , it has been pointed out that the development of insulin resistance as a consequence of a chronic inflammatory state and oxidative stress could be implicated in the association between obesity and periodontitis . | BACKGROUND Obesity is a very prevalent chronic disease worldwide and has been suggested to increase susceptibility of periodontitis .
The aim of this paper was to provide a systematic review of the association between obesity and periodontal disease , and to determine the possible mechanisms underlying in this relationship . | BACKGROUND AND OBJECTIVE This cross-sectional case-control study was conducted to provide a comparative evaluation of clinical periodontal measurements , together with serum levels of certain bioactive peptides and inflammatory cytokines , in relation to obesity . For this purpose , clinical periodontal measurements and the levels of serum leptin , adiponectin , interleukin-6 ( IL-6 ) , C-reactive protein and soluble intercellular adhesion molecule-1 of obese female individuals and their nonobese counterparts were compared . MATERIAL AND METHODS Sixty obese ( body mass index ( BMI ) > 30 ) and 31 nonobese ( BMI < 30 ) female subjects were recruited for the present study . Before any periodontal intervention , serum sample s were obtained and full-mouth clinical periodontal measurements were recorded at six sites per tooth . ELISA was used for the biochemical analysis . Data were tested statistically . RESULTS Clinical attachment level was significantly higher in the obese group compared with the nonobese control group ( p < 0.05 ) . Serum levels of leptin and IL-6 were significantly higher in the obese group ( p < 0.05 ) . BMI correlated with the serum levels of inflammatory molecules ( p < 0.05 ) , but not with clinical periodontal parameters , in the obese group . CONCLUSION In conclusion , obesity does not seem to have a prominent effect on clinical periodontal parameters but it does have many correlations with circulating inflammatory molecules . As suggested in the literature , increased levels of leptin and IL-6 in the obese group might be one explanation for a possible relationship between obesity and periodontal disease . A prospect i ve study is warranted to clarify , in greater detail , the effects of obesity on periodontal health AIM The purpose of this prospect i ve cohort study was to investigate whether body mass index ( BMI ) and oral health behaviour are related to changes in periodontal status in Japanese university students . MATERIAL S AND METHODS Students ( n = 224 ) who were interested in receiving oral health examinations before entering university and before graduation were included in the analysis . Subjects were investigated regarding the correlations of oral health behaviours and increases in BMI with the percentage of bleeding on probing ( % BOP ) and Community Periodontal Index ( CPI ) scores as indicators of changes in periodontal status . RESULTS The risk of increased % BOP was associated with the non-use of dental floss ( adjusted odds ratio [ OR ] : 3.11 ; 95 % confidence interval [ CI ] : 1.31 - 7.37 ; p < 0.05 ) , whereas the risk of increased CPI score was associated with increases in BMI ( OR : 1.95 ; 95 % CI : 1.05 - 3.65 ; p < 0.05 ) and simplified oral hygiene index score ( OR : 2.28 ; 95 % CI : 1.23 - 4.22 ; p < 0.01 ) . CONCLUSION Increases in BMI were associated with worsening of periodontal status , defined as increased CPI score in Japanese university students , whereas lack of inter-dental cleaning was associated with exacerbated gingival bleeding OBJECTIVE To investigate the effect of conventional periodontal therapy on serum C-reactive protein ( CRP ) level and periodontal status in obese and normal-weight chronic periodontitis patients . METHODS This is a controlled clinical trial conducted at the King Abdulaziz University Faculty of Dentistry , Jeddah , Kingdom of Saudi Arabia between December 2009 and March 2011 . A total of 40 women affected with moderate to severe chronic periodontitis were selected ( 20 obese [ test group ] and 20 normal-weight [ control ] ) . Smokers , pregnant women , and subjects with any systemic disease were excluded . Serum CRP level and periodontal parameters , including clinical attachment level , probing depth , bleeding on probing and plaque scores were assessed at baseline , and 2 months after non-surgical periodontal treatment . RESULTS Periodontal therapy was effective in reducing gingival inflammation , as well as serum CRP level in the total sample and within each group . The pre-treatment mean level of serum CRP was 0.78 ( + /-0.51 ) and post- treatment was 0.55 ( + /-0.41 ) mg/l in the total sample ( p=0.001 ) . A tendency was observed toward a better systemic response to treatment in normal-weight compared to obese women , however , it was not statistically significant ( the mean changes in CRP levels after therapy were 0.28 [ + /-0.43 ] and 0.19 [ + /-0.32 ] mg/l ) . CONCLUSION Periodontal treatment is effective in reducing systemic inflammation as measured by serum CRP level , and obesity does not have a major negative impact on response to periodontal therapy BACKGROUND Earlier studies have shown an association between obesity and periodontitis , which is mediated by cytokine production . The aim of this study is to assess the role of obesity as a modifying factor on periodontal clinical parameters and on circulating proinflammatory cytokine levels in subjects undergoing non-surgical periodontal treatment . METHODS Twenty-seven obese subjects and 25 normal-weight subjects were enrolled in this study . Subjects in both groups had generalized chronic periodontitis . The periodontal parameters measured before and 3 months after non-surgical periodontal therapy were : visible plaque index , bleeding gingival index , bleeding on probing , probing depth , and clinical attachment level . In addition , subjects underwent anthropometric measurements and serum analyses of fasting glucose , glycated hemoglobin , interleukin-1β , interleukin-6 , tumor necrosis factor-α , and interferon-γ . RESULTS Periodontal therapy significantly decreased visible plaque index , bleeding gingival index , bleeding on probing , probing depth of 4 to 6 mm , probing depth ≥7 mm , clinical attachment level of 4 to 6 mm , and clinical attachment level ≥7 mm in both groups ( P ≤0.05 ) . Circulating proinflammatory cytokines significantly decreased in obese and normal-weight subjects after periodontal treatment ( P ≤0.05 ) . However , interleukin-6 and tumor necrosis factor-α levels remained higher in obese subjects 3 months after treatment ( P ≤0.05 ) . CONCLUSION Obesity does not seem to play a negative role by interfering in the improvement of the periodontal clinical response or decreasing circulating proinflammatory cytokine levels after periodontal treatment |
11,112 | 27,503,701 | In summary , this meta- analysis supports that AH was associated with an increased chance of achieving clinical pregnancy and multiple pregnancy . | Emerging evidence suggests that assisted hatching ( AH ) techniques may improve clinical pregnancy rates , particularly in poor prognosis patients ; however , there still remains considerable uncertainty .
We conducted a meta- analysis to verify the effect of AH on pregnancy outcomes . | BACKGROUND Cryopreservation of embryos may lead to zona hardening that may compromise in vivo hatching and implantation following thawing and transfer . Assisted hatching ( AH ) has been advocated as a means of assisting the natural hatching process and enhancing implantation . METHODS The aim of this study was to assess in a prospect i ve r and omized manner the effect of laser-assisted hatching ( LAH ) on implantation as well as clinical and multiple pregnancy rates ( the primary outcome ) after the transfer of frozen-thawed embryos . All embryos were thawed the day before transfer , and LAH was performed the next day on embryos that cleaved . Control group consisted of embryos that were transferred without AH . RESULTS The performance of LAH significantly increased implantation ( 9.9 versus 20.1 % , P < 0.01 ) , clinical pregnancy ( 27.3 versus 40.9 , P < 0.05 ) and multiple pregnancy rates ( 16 versus 40.3 % , P < 0.07 ) . In the LAH group , significantly more excess embryos that were left in culture hatched in vitro . CONCLUSIONS LAH improves the outcome of frozen-thawed embryo transfer when performed before transfer on embryos that were allowed to cleave Background : Routine use of assisted hatching ( AH ) following ICSI is a controversial issue in the literature . There are rare studies regarding the effect of laser assisted hatching ( LAH ) on live birth rate . Objective : Our main goal was to evaluate the effect of LAH on delivery rate as well as congenital anomaly in patients undergoing their first ICSI cycle . Material s and Methods : A total of 182 patients subjected to ICSI were r and omly aliquot into two groups of experiment and control . In experiment group , the embryos were subjected to LAH to open a hole in ZP ( about 10 - 12 µm ) while in control group , the transferred embryos were intact with no AH . The patients were followed for clinical pregnancy and delivery rate as well as congenital anomaly . All the patients were infertile due to male factor infertility and LAH and embryo transfer were done on day 2 . Results : Laboratory and clinical characteristics of two groups of experiment and control were the same . There were insignificant differences between two groups of experiment and control for clinical pregnancy rate ( 20 % vs. 23.9 % , respectively , p=0.3 ) and live birth rate ( 11.11 % vs. 8.6 % , respectively , p=0.6 ) . Also no significant differences were observed between two groups of experiment and control for multiple pregnancy as well as congenital anomaly . Conclusion : Routine use of LAH in first ICSI cycle for male factor patients may have no beneficial effects on clinical pregnancy and live birth rate The objective of this study was to determine if assisted hatching improved the rates of implantation , clinical pregnancy and ongoing pregnancy for in-vitro fertilization ( IVF ) patients aged > or = 36 years . On the day of oocyte aspiration , consenting patients were r and omized according to whether all embryos underwent the hatching procedure ( hatched ; n = 41 ) or all embryos remained unhatched ( controls ; n = 48 ) . Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days . The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode 's medium against the zona pellucida to create an opening approximately 20 microm in diameter . No significant differences were noted in the mean age , number of oocytes aspirated and number of embryos transferred between the hatched and control groups . In addition , no significant differences were observed in the rates of implantation ( 11.1 versus 11.3 % ) , clinical pregnancy ( 39.0 versus 41.7 % ) and ongoing pregnancy ( 29.3 versus 35.4 % ) between the hatched and control groups respectively . These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied Abstract Purpose : The role of assisted hatching in good-prognosis IVF patients was evaluated in a prospect i ve , r and omized , controlled pilot study , which was followed by a retrospective observational series . Methods : After assisted hatching was proved successful in a mouse embryo study , 20 good-prognosis IVF patients were r and omly assigned to either assisted hatching ( 13 ) or no assisted hatching ( 7 ; the controls ) . Following this series , 27 good-prognosis IVF patients were retrospectively evaluated to determine the outcome with assisted hatching . Results : In the prospect i ve study , clinical pregnancies result ed from 3 ( 23 % ) of 13 patients in the hatching group , compared to 3 ( 43 % ) of 7 in the control group . Implantation rates were similar : 9.6 % in the hatching group and 10.7 % in the controls . In the retrospective series , the 11.1 % implantation rate with assisted hatching was significantly less than the 42.9 % implantation rate seen with traditional IVF . Conclusions : Implantation and pregnancy rates are high in young women undergoing traditional IVF . Assisted hatching is not beneficial in these patients 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 assess the effect of augmenting IVF with assisted hatching in the treatment of patients with repeated IVF failures . DESIGN Prospect i ve r and omized study . SETTING Division of Reproductive Endocrinology and Infertility of National Taiwan University Hospital . PATIENT(S ) From July 1993 to February 1996 , 49 patients with repeatedly failed IVF were treated with assisted hatching and were compared with 51 control subjects without assisted hatching . INTERVENTION(S ) Assisted hatching . MAIN OUTCOME MEASURE(S ) Pregnancy rate and implantation rate per embryo after IVF-ET or IVF-tubal ET ( TET ) were measured . RESULT ( S ) The pregnancy rate ( PR ) in the assisted hatching group was found to be 36.7 % compared with 19.6 % in the control group , but the difference was not significant . When only patients receiving IVF-ET were considered , it was observed that the PR was significantly higher in the assisted hatching group than the control group ( 42.4 % versus 16.1 % ) . With IVF-TET however , the PR was found to be similar in both assisted hatching and control groups ( 25.0 % and 25.0 % , respectively ) . The rate of embryonic implantation in the IVF-ET patients was 11.0 % , which was significantly higher than that of control embryos ( 3.7 % ) . CONCLUSION ( S ) These results implied that IVF-ET , combined with assisted hatching , may improve the PR and implantation rate in patients with repeated IVF failures , but the same was not true in the case of IVF-TET In two separate prospect ively r and omized trials , intracytoplasmic sperm injection ( ICSI ) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture ( n = 119 ) or assisted hatching by zona drilling ( n = 100 ) . In the first study , immediately following ICSI , all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium . Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells , ultimately there were no significant differences in either the viable pregnancy rate ( 31.6 % co-culture versus 29.0 % control ) or the embryonic implantation rate ( 11.4 % co-culture versus 13.6 % control ) . Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate ( 30.0 % assisted hatching versus 32.0 % control ) or the embryonic implantation rate ( 8.5 % assisted hatching versus 13.5 % control ) . However , in female patients aged > or = 35 years , assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate ( 35.5 % assisted hatching versus 11.1 % control ) and the embryonic implantation rate ( 10.3 % assisted hatching versus 3.1 % control ) . It seems that the overall improvement of ICSI cycle outcome can not be achieved by the general application of either co-culture or assisted hatching . Nevertheless , it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities BACKGROUND Assisted hatching ( AH ) in fresh embryo transfer ( ET ) cycles increases the implantation and pregnancy rates , especially in women with a poor prognosis , repeated implantation failures and in older women . Little information exists in the literature regarding the role of AH in frozen-thawed embryo transfer ( FET ) cycles . METHODS Embryos were cryopreserved at the cleavage stage . On the day of FET , 160 patients were r and omized according to a computer-generated r and omization list in sealed envelopes into the AH group and the control group . The patients and the clinicians were blinded to the group assigned . In the AH group , the outer half of the zona pellucida over a quarter of the diameter of zona was removed using a 1480 nm non-contact laser . RESULTS The two groups were comparable in terms of demographic characteristics , ovarian response of the stimulated cycle and quality of fresh and frozen-thawed embryos . No differences in implantation , pregnancy and multiple pregnancy rates were found between the two groups . There was a non-significant trend of a higher implantation rate in the AH group when the zona thickness was > or = 16 mm . CONCLUSION Laser AH did not improve the implantation rate of FET cycles and should not be performed routinely in all frozen-thawed embryos at the cleavage stage Abstract Purpose : The objective of this study was to determine if the zona thinning ( ZT ) technique improved the rates of implantation and clinical pregnancy for patients aged ≥38 years su bmi tted to an ICSI program . Methods : A total of 100 patients su bmi tted to ICSI and aged ≥38 years were divided in a prospect i ve and r and omized manner into two groups : Group I – patients su bmi tted to ZT ( n = 50 ) ; a laser diode with 1.48 μm wavelength ( Fertilaser ) was used for the ZT procedure with 1–2 irradiations of 10 ms applied to four different positions on the zona pellucida ( ZP ) of each embryo to thin 60–90 % of the ZP ( each point with a 15–20 μm length of ZT ) . Group II – patients with no ZT ( n = 50 ) . In both groups , embryo transfer was performed on the second or third day . Results : The age of Group I patients ( 39.8 ± 1.3 ) did not differ ( p = 0.67 ) from that of Group II patients ( 40 ± 1.9 ) . The number of oocytes retrieved at metaphase II from Group I ( 6.4 ± 4.2 ) and Group II ( 6.8 ± 5 ) was similar ( p = 0.94 ) . Normal fertilization rates and cleavage rates were similar ( p = 0.78 and p = 0.63 , respectively ) for Group I ( 71.5 ± 22 % and 96.7 ± 11 % ) and Group II ( 73.5 ± 19.7 % and 96 ± 11 % , respectively ) . The number of embryos transferred was similar ( p = 0.53 ) for the two groups ( Group I = 3.1 ± 1.3 ; Group II = 2.9 ± 1.1 ) . The thickness of the ZP of Group I embryos ( 16.9 ± 2.4 μm ) did not differ ( p = 0.97 ) from that of Group II embryos ( 16.9 ± 2.3 μm ) . The rates of embryo implantation and clinical pregnancy per embryo transfer were similar ( p = 0.67 , p = 0.61 ) for Group I ( 7 and 16 % , respectively ) and for Group II ( 8.2 and 22 % , respectively ) . Conclusions : These results suggest that ZT in the population aged ≥38 years may have no impact on ICSI success rates . However , this conclusion is limited to a situation in which length of the laser ZT was ≤20 μm and the laser was applied to four different positions Implantation failure after IVF is one of the factors associated with a reduced chance of pregnancy for some patients . Assisted hatching method ologies are design ed to facilitate the embryo 's escape from the zona pellucida , and this strategy has been suggested as a means of improving pregnancy rates in patients with previous implantation failure . The aim of this prospect i ve and r and omized study was to evaluate the efficacy of quarter-laser zona thinning assisted hatching ( qLZT-AH ) in improving the implantation of embryos in patients with previous implantation failure . A total of 150 patients with a history of previous implantation failure were treated with intracytoplasmic sperm injection , and allocated into two groups : group 1 , only one previous implantation failure , and group 2 , repeated implantation failures . The patients in each group were r and omized at the time of embryo transfer into a control group ( no qLZT-AH ) or experimental group where qLZT-AH was performed . For patients with repeated implantation failures , the implantation rate in those who received laser-thinned embryos was significantly higher ( P = 0.02 ) than in those whose embryos were not laser-thinned ( 10.9 and 2.6 % respectively ) . However , this difference was not observed in patients who presented with only one previous implantation failure . The data demonstrate that qLZT-AH is an effective strategy for improving the implantation of embryos in patients with repeated implantation failures Abstract Purpose : Preliminary data from some research centers indicate that assisted hatching might be of value to increase embryo implantation rate in the human , at least in selected cases . It is not clear , however , whether this technique would be of benefit for all patients undergoing an embryo transfer . We therefore performed a prospect i ve r and omized study to evaluate the effect of assisted hatching on the implantation rate in our in vitro fertilization (IVF)/intracytoplasmic sperm injection ( ICSI ) program . Methods : In total , 120 couples undergoing an embryo transfer were r and omized between two groups : in one group no assisted hatching was performed ( AH− ) , whereas in the other group the embryos selected for transfer were subjected to partial zona dissection ( PZD ) immediately prior to the transfer ( AH+ ) . Using a computer-generated minimization procedure , patients were allocated to one of the two groups according to four preselected criteria : the number of embryos transferred , the cumulative score of transferred embryos , the age of the patient , and the use of ICSI . Results : Pregnancy and implantation rates in the AH+ and AH− groups were , respectively , 42.1 versus 38.1 % and 17.9 versus 17.1 % . Conclusions : From our data we conclude that assisted hatching through partial zona dissection prior to embryo transfer does not improve pregnancy and embryo implantation rates in unselected patients undergoing IVF or ICSI BACKGROUND Assisted hatching can improve the implantation rate in cycles with poor outcome . The impact of assisted hatching in embryos from women with endometriosis is not known . Therefore , the hypothesis that the implantation potential of embryos obtained from women with endometriosis can be improved with assisted hatching was tested . METHODS In a prospect i ve r and omized study , transfer embryos obtained from 60 women with endometriosis were hatched using a laser system and compared to embryos obtained from patients with the same diagnosis which were left intact ( n = 30 ) . RESULTS The characteristics of cycles were similar between groups . The pregnancy ( 40 % zona intact , 28.3 % assisted hatching ) , and implantation rates ( 19.4 % zona intact , 17.8 % assisted hatching ) did not differ in endometriosis cycles regardless of assisted hatching . CONCLUSION Assisted hatching does not improve outcome in women with endometriosis undergoing assisted reproduction The aim of this study was to evaluate the effects of quarter zona-pellucida ( ZP ) opening by laser-assisted hatching ( QLAH ) on the clinical outcomes following transfer of vitrified-warmed blastocysts developed from low- grade cleavage-stage embryos in patients with all high- grade and fair- grade cleavage-stage embryos transferred without achieving pregnancy . Patients were r and omized into two groups : QLAH ( n=101 ) and control ( n=102 ) . The implantation and clinical pregnancy rates were significantly higher in the QLAH group compared with the control group ( P=0.021 and P=0.034 , respectively ) . The live birth rate of the QLAH group was also higher , although not significantly . When the clinical outcomes according to the day of blastocyst vitrification were compared between the groups , the implantation , clinical pregnancy and live birth rates of the QLAH group were significantly higher ( P<0.05 ) than those of the control group for day 6 blastocysts , but not for day 5 or day 5/day 6 blastocysts . These results suggest that QLAH improves the clinical outcomes of vitrified-warmed blastocysts , especially of day 6 vitrified blastocysts , developed from low- grade cleavage-stage embryos BACKGROUND Assisted hatching ( AH ) techniques , design ed for facilitating the embryo escape out of the zona pellucida ( ZP ) have been used in IVF centres since 1992 . The initial indications for AH were patient 's age , ZP thickness , high basal FSH and repeated IVF failures . Several retrospective and prospect i ve studies assessing AH in these indications have given disparate results . Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment ( IA ) in patients with either a poor prognosis of success , previous implantation failures or transfers of cryopreserved embryos . METHODS Four IVF centres allocated 426 patients , r and omized for AH and IA , into four groups of AH indications between 1997 and 1999 . AH was performed with a diode laser . ZP thickness , opening size and embryo score were recorded . Outcome measures were implantation and delivery rates . RESULTS Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH . Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH . CONCLUSIONS Among AH indications , absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion . Prescription of an immunosuppressive/antibiotic treatment is essential OBJECTIVE To compare the outcome of zona-intact versus zona-free blastocyst transfer . DESIGN Prospect i ve , r and omized study . SETTING Tertiary care private hospital IVF center . PATIENT(S ) A total of 240 patients undergoing blastocyst stage ET ( 119 zona intact and 121 zona free ) . INTERVENTION(S ) In vitro culture of embryos to the blastocyst stage was followed by r and om allocation to zona-intact or zona-free transfer . MAIN OUTCOME MEASURE(S ) Treatment cycle characteristics , implantation , and pregnancy rates . RESULT ( S ) Transfer of zona-free blastocysts was associated with a higher implantation rate . Subgroup analysis , however , indicated that better outcome was achieved only in the group that received poor- quality blastocysts . Patients undergoing blastocyst transfer for the first time did not seem to benefit from zona-free blastocyst transfer . CONCLUSION ( S ) Zona-free blastocyst transfer increases the success of blastocyst-stage transfer in patients with poor- quality blastocysts OBJECTIVE To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida ( ZP ) . DESIGN Prospect i ve , r and omized , double-blinded , crossover study . SETTING University-based infertility center . PATIENT(S ) One hundred twenty-one women less than 38 years of age , undergoing IVF at Washington University between April 2004 and February 2007 , with ZP thickness > or = 13 microm for any embryos . INTERVENTION(S ) Measurement of ZP thickness in embryos undergoing IVF ; r and omization of women with embryos with ZP thickness > or = 13 microm to no procedure or assisted hatching performed by acidic Tyrode 's solution . MAIN OUTCOME MEASURE(S ) Clinical intrauterine pregnancy rate , implantation rate , spontaneous pregnancy loss , and live birth rate . RESULT ( S ) Baseline characteristics and ZP thickness were not significantly different between the two study arms ( hatched and unhatched ) . No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy ( 47 % vs. 50 % respectively ) or live birth ( 46 % vs. 45 % respectively ) . Further , no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions , monozygotic twinning , dizygotic twinning , chromosomal abnormalities , or ectopic gestations . In addition , mean ZP thickness did not have a significant effect on pregnancy . CONCLUSION ( S ) In patients younger than 38 years with embryos with ZP thickness of > or = 13 microm , assisted hatching does not improve the rates of implantation , clinical pregnancy , or live birth , and thus does not appear to offer any benefit to patients in this age group undergoing IVF Assisted hatching by zona drilling using acidic Tyrode 's solution was performed during three r and omized trials in 330 in-vitro fertilization patients . The trials were design ed in order to study the overall effect of the procedure and whether characteristic patient [ i.e. maternal age and basal levels of follicle stimulating hormone ( FSH ) ] and embryonic features ( i.e. zona pellucida thickness ) are important for the decision to perform assisted hatching routinely . Couples ( n = 137 ; Trial 1 ) in whom the female partner had normal basal FSH levels were r and omized in a control group ( without micromanipulation ) and a zona drilling group ( all embryos micromanipulated ) . The incidence of implantation ( 67/239 ; 28 % ) of zona-drilled embryos compared favourably with that of control embryos ( 49/229 ; 21 % ) , but the difference was not significant . Retrospective analysis revealed that those embryos whose zonae were thicker than 15 microns were rescued . In order to test the validity of this finding , selective assisted hatching was performed on embryos with a poor prognosis in 163 other patients ( Trial 2 ) . The couples were r and omized into a control group and a group in which embryos were selectively zona-drilled , based on zona thickness and other embryonic features . The rate of embryonic implantation in the selectively zona-drilled group was 25 % ( 70/278 ) , significantly ( P less than 0.05 ) higher than that of control embryos ( 51/285 ; 18 % ) . Although it was demonstrated retrospectively and prospect ively that assisted hatching by zona drilling is effective in embryos with thick zonae ( greater than or equal to 15 microns ) , patients whose embryos have thin ( less than 13 microns ) zonae may be jeopardized by the procedure . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To evaluate the implantation rate achieved after chemical removal of the zona pellucida from day 5 human in vitro-derived embryos . DESIGN Prospect i ve , r and omized , controlled study . SETTING A tertiary care infertility clinic . PATIENT(S ) Two hundred fifty-seven patients undergoing IVF with transfer of morulas or blastocysts on day 5 after oocyte retrieval . All patients had had at least two previous implantation failures . INTERVENTION(S ) Chemical removal of zona pellucida by using acidic Tyrode 's solution vs. no removal ( controls ) . MAIN OUTCOME MEASURES Clinical pregnancy rate and implantation rate per transfer . RESULT ( S ) Embryos without zona pellucida implanted at nearly twice the rate of control embryos ( 15.7 % vs. 27.5 % ) . The pregnancy rate was also significantly higher in the zona pellucida-free group than the control group ( 31.0 % vs. 46.1 % ) . Removal of zona pellucida was most effective in embryos with delayed development , which reached the morula or early cavitating stage on day 5 of in vitro culture ( implantation rate , 12.1 % vs. 25.7 % ) . CONCLUSION ( S ) Chemical removal of zona pellucida from day 5 in vitro cultured human embryos is an effective and safe method of significantly improving the implantation rate , especially of embryos with delayed development Abstract Purpose : In this prospect i ve r and omized study the effectsof enzymatic treatment of zona pellucida of blastocysts onimplantation and pregnancy rates were evaluated in a groupof patients who had more than five embryos on day 3 . Methods : Forty-six patients with a mean age of 29.8 ± 4.5years and mean duration of infertility of 6.72 ± 0.63 yearshad blastocyst stage transfers , with a mean number of2.9 ± 0.1 embryos replaced per patient . Patients were r and omlydivided into two groups . The first group consisted of patients ( n = 22 ) who had zona intact blastocyst stagetransfers and the second group consisted of patients ( n = 24)who had zona manipulated ( enzymatic treatment ) blastocyststage transfers . Patient and cycle characteristics were similarin both groups . A commercial cell and serum-free sequentialculture system was used for all embryos . Results : Overall blastocyst formation rate was 50.3%.Transfer could be done in all patients . The positive β-humanchorionic gonadotropin rate in the zona intact group was50 % ( 11/22 ) and in the zona-manipulated group was 70.8%(17/24 ) . Clinical pregnancy , ongoing pregnancy , and implantation rates in zona intact and manipulated groupswere 45.5 % , 27.3 % , and 19 % , and 62.5 % , 45.8 % , and 24%respectively . Although implantation and pregnancy rates inthe zona-manipulated group were higher , there were nostatistically significant differences in terms of these variablesbetween two groups . No triplet pregnancy was obtained ineither group , and the twin pregnancy rate was 20 % (2/10)in the zona intact group and 13.3 % ( 2/15 ) in thezonamanipulated group . Conclusions : With further improvements in the embryoculture systems it will become possible in the near future toachieve high implantation rates even with single blastocysttransfers . Enzymatic treatment of the zona pellucida seemsthat it does not alter the pregnancy and implantation rates , but further studies with larger group of patients are neededto clarify the real effect of this zona manipulation onpregnancy outcome Abstract Purpose : Zona thinning ( ZT ) is a technique used to improve pregnancy rates among patients ≥38 years old and /or patients presenting previous implantation failure . The objective of the study was to determine whether ZT has a beneficial effect on patients younger than 37 years who are undergoing the first ICSI attempt . Methods : A total of 103 patients su bmi tted to ICSI for the first time and those aged ≤37 years were divided in a prospect i ve and r and omized manner into two groups : group I , patients su bmi tted to ZT ( n = 51 ) ( a laser diode with 1.48-μm wavelength ( Fertilaser ) was used for the procedure ) ; group II , patients with no ZT ( n = 52 ) . In both groups , embryo transfer was performed on the second day . Results : The age of group I patients ( 31.8 ± 3.6 ) did not differ ( P = 0.53 ) from that of group II patients ( 31.4 ± 3.6 ) . The number of metaphase II oocytes was similar(P = 0.76 ) for the two groups ( group I = 9.12 ± 5.27 ; group II = 8.67 ± 5.02 ) . The average number of embryos available per transfer of group I ( 6.14 ± 4.02 ) did not differ ( P = 0.69 ) from that of group II ( 5.75 ± 3.83 ) . The number of embryos transferred was similar ( P = 0.61 ) for the two groups ( group I = 2.76 ± 0.9 ; group II = 2.87 ± 0.79 ) . The thickness of the zona pellucida of group I embryos ( 16.6 ± 2.2 μm ) did not differ ( P = 0.08 ) from that of group II embryos ( 17.1 ± 1.7 μm ) . The rate of embryo implantation ( 20.8 % ) and the rate of clinical pregnancy per embryo transfer ( 40.3 % ) were higher for group II than for group I ( 17.7 % and 33.3 % , respectively ) , but the difference was not significant ( P = 0.55 and P = 0.54 ) . Conclusions : These results suggest that ZT in the population aged ≤37 years and with no previous failure of implantation may have no impact on intracytoplasmic sperm injection success rates OBJECTIVE To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients , defined as patients < or = 39 years with normal follicle-stimulating hormone ( FSH ) and E(2 ) levels , no more than one previous unsuccessful cycle of in vitro fertilization (IVF)-embryo transfer , and good embryo quality . DESIGN Prospect i ve r and omized controlled trial . SETTING Private assisted reproductive technology ( ART ) center . PATIENT(S ) One hundred ninety-nine good prognosis patients undergoing IVF-embryo transfer . INTERVENTION(S ) In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser . MAIN OUTCOME MEASURE(S ) Clinical intrauterine pregnancy , spontaneous pregnancy loss , and live birth . RESULT ( S ) Rates of clinical intrauterine pregnancy with fetal cardiac activity ( 53 % vs. 54 % per cycle ) , spontaneous pregnancy loss ( 13 % vs. 16 % per pregnancy ) , and live birth ( 47 % vs. 46 % per cycle ) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching . There were no significant differences between treatment and control groups in any measured clinical outcome parameters . CONCLUSION ( S ) Assisted hatching does not improve clinical outcomes among good prognosis patients Two hundred eighteen consenting patients entered a r and omized study of the application of chemical zona pellucida thinning on their day 3 embryos , prior to uterine transfer . Of those control patients ( n = 108 ) , whose embryos remained unmanipulated , 40 ( 37.0 % ) have ongoing/delivered pregnancies , while in the experimental group ( n = 110 ) , whose embryos had their zonae pellucidae chemically thinned , there are 49 patients ( 44.6 % ) who have ongoing/delivered pregnancies . Although this difference is not significant , clearly the application of this micromanipulative intervention has not been detrimental , and this bodes well for routine application of embryonic micromanipulation procedures in general . Certain patient subgroups were studied including older women , those with elevated basal follicle stimulating hormone levels , patients with embryos of differing zona thickness , and patients with embryos of differing uniformity of zona thickness . No significant influence of chemical removal of the outside of the zona on the implantation rate of embryos in any of these subgroups was observed other than a marginally significant ( P = 0.095 ) improvement of implantation of embryos with less than 4.0 µm variation in zona thickness when chemical zona thinning was applied . Failure of chemical zona thinning to enhance human embryo implantation significantly , compared to assisted hatching by complete zona drilling , strongly suggests that the bilayered human zona pellucida needs to be fully breached , unlike that of the mouse BACKGROUND Assisted hatching ( AH ) has been proposed as a means to increase the implantation rate in patients with poor prognosis for pregnancy . The procedure appears to be effective when used selectively . Several different methods for AH have been introduced over the years but comparative studies are lacking . The aim of the current study was to compare retrospectively the efficacy of AH performed with four different methods in patients undergoing IVF or ICSI . METHODS AH was performed prior to day 3 embryo transfer in 794 IVF/ICSI cycles . Indications for AH were females aged > 35 years and /or elevated follicular phase FSH levels , previous failed IVF/ICSI cycles , poor embryo quality , and thick zona pellucida ( > 15 microm ) . Assignment to one of the four methods of AH was according to the availability of the particular method during the study period . The study was not r and omized . RESULTS Partial zona dissection was used in 239 , acid Tyrode in 191 , diode laser in 219 and pronase thinning of the zona pellucida in 145 . Mean female age , mean number of previous failed IVF/ICSI cycles , number of oocytes retrieved , fertilization and cleavage rates , good quality embryos and zona thickness on day 3 did not differ between groups . Mean number of embryos transferred , implantation rate , clinical pregnancy rate , and abortion rates were likewise similar . CONCLUSIONS Selective AH using four different methods yields similar implantation and pregnancy rates OBJECTIVE To assess trends and outcomes of assisted hatching among assisted reproductive technology ( ART ) cycles . DESIGN Retrospective cohort analysis using National ART Surveillance System ( NASS ) data . SETTING U.S. fertility centers reporting to NASS . PATIENT(S ) Fresh autologous noncanceled ART cycles conducted from 2000 - 2010 . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Implantation , clinical pregnancy , live-birth , miscarriage , multiple gestation . RESULT ( S ) Assisted hatching use statistically significantly increased in absolute number ( from 25,724 to 35,518 cycles ) , percentages of day-3 ( from 50.7 % to 56.3 % ) and day-5 transfers ( from 15.9 % to 22.8 % ) , and percentage of transfers among women ≥38 years ( from 17.8 % to 21.8 % ) or women with ≥2 prior ART cycles and no live birth(s ) ( from 4.3 % to 7.4 % ) . Both day-3 and day-5 cycles involving assisted hatching were associated with lower odds of implantation ( adjusted odds ratios [ aOR ] 0.7 and 0.6 , respectively ) , clinical pregnancy ( aOR 0.8 and 0.7 , respectively ) , live birth ( aOR 0.8 and 0.7 , respectively ) , and increased odds of miscarriage ( aOR 1.4 and 1.4 , respectively ) , as compared with cycles without assisted hatching . Assisted hatching was associated with lower odds of multiple gestation in day-5 cycles ( aOR 0.8 ) . In cycles for women with a " poor prognosis , " the association of assisted hatching with pregnancy outcomes was not statistically significant . CONCLUSION ( S ) Assisted hatching use had an increasing trend but was not associated with improved pregnancy outcomes , even in poor-prognosis patients . Prospect i ve studies are needed to identify the patients who may benefit from assisted hatching PURPOSE To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles . DESIGN Prospect i ve r and omized study . SETTING IVF unit of an academic medical center . PATIENTS Women who underwent IVF after at least three failed IVF-ET attempts . INTERVENTIONS Patients were prospect ively r and omized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection . RESULTS The study ( assisted hatching ) and control groups included 104 and 103 patients , respectively . There were no significant between-group differences in patient age , cause of infertility , mean number of previous IVF trials , number of oocytes retrieved , fertilization rate , or number of embryos transferred . No difference in pregnancy rate was noted on comparison of the whole study group , to the whole control group ( 21 % and 27 % , respectively ) . However , when the results were re-analyzed by age groups , assisted hatching was found to be harmful in the youngest group ( < 34 years ) , significantly decreasing pregnancy rates ( 15 % vs 35 % , p < 0.05 ) . CONCLUSION Repeated implantation failure alone is not an indication for assisted hatching . Although assisted hatching appears to be effective in a selected group of older patients , in younger patients it may further hamper implantation and should be avoided The objective of this prospect i ve r and omized double-blind clinical trial was to evaluate whether laser zona pellucida thinning of human embryos improves clinical outcomes in women < or=37 years old undergoing IVF-ET treatment . The study did not reveal any significant beneficial effect of laser zona thinning on clinical pregnancy ( 16 out of 45 vs. 18 out of 39 ) and live birth rates ( 13 out of 45 vs. 16 out of 39 ) between the laser-treated and nontreated groups of patients , although there was a trend toward an increased incidence of dichorionic multiple pregnancies in the study group compared with the control group ( 7 out of 13 vs. 4 out of 16 ) OBJECTIVE To compare the clinical outcomes of patients whose transferred embryos underwent either laser-assisted hatching or hatching with acidified medium . DESIGN R and omized , prospect i ve , double-blinded study . SETTING University-based IVF center . PATIENT(S ) Clinical outcomes following IVF were compared in 159 patient cycles who r and omly had all transferred embryos undergo laser-assisted hatching ( Laser ; n = 57 ) or hatching with acidified medium ( Acid ; n = 54 ) . Patients whose embryos had zonae thickness < 13 mum were not hatched ( Thin ; n = 8) and patients with > or = 4 embryos at the 7- to 8-cell stage or higher on Day 3 were transferred on Day 5 ( Day 5 ; n = 40 ) . MAIN OUTCOME MEASURE(S ) Implantation rates , clinical pregnancy rates , ongoing pregnancy rates , multiple pregnancy rates . RESULT ( S ) No significant differences were noted in clinical , ongoing , or multiple pregnancy rates between the four groups . The implantation rate for Day 5 transfers was significantly greater than both the Laser and Acid treatment groups . CONCLUSION The use of a 1.48-micron infrared diode laser beam provides a safe and rapid method for performing assisted hatching and did not have a negative impact on patient care when compared to outcomes achieved using acidified medium Laser-assisted hatching is little documented in the literature regarding its efficacy in cryopreserved-thawed ( CT ) embryo transfer cycles . The aim of the present study was to evaluate in a r and omized manner the efficacy of thinning one quarter of the zona pellucida of CT embryos to a depth of 50 - 80 % of the original thickness , via laser treatment ( the qLZT-AH procedure ) , in improving implantation and pregnancy rates . Two population s were studied : population I , patients who had all their supernumerary embryos cryopreserved , regardless of their morphology , and population II , patients at risk of ovarian hyperstimulation syndrome who had all their embryos cryopreserved . Artificial and natural protocol s were used for the embryo transfers . A total of 350 laser-thinned CT embryos were compared with 352 intact zona embryos . No difference in implantation or pregnancy rate was found after using qLZT-AH in either population . These findings suggest that qLZT-AH should not be routinely performed in cryopreserved embryo programmes The aim of this study was to determine if assisted hatching ( AH ) could improve the rates of pregnancy and implantation for both fresh and frozen-thawed embryo transfer cycles . A total of 760 fresh embryo transfer cycles and 200 frozen-thawed embryo transfer cycles were r and omly assigned to either the treatment group ( AH ) or the control group ( no AH ) . Zona thinning by laser was performed just before embryo transfer . In fresh embryo transfer cycles , the AH group and control group results were comparable . There were no significant differences in the rates of positive human chorionic gonadotrophin ( HCG ; 47.5 versus 48.8 % ) , clinical pregnancy ( 42.4 versus 42.6 % ) , or implantation ( 26.3 versus 25.2 % ) between the two groups . However , in frozen-thawed embryo transfer cycles , the rates of positive HCG ( 32.0 versus 17.0 % ) , clinical pregnancy ( 25.0 versus 14.0 % ) and implantation ( 16.7 versus 7.3 % ) were significantly greater in the AH group than in the control group ( P < : 0.05 ) . The results of this investigation show that in the fresh embryo transfer cycles , laser-assisted hatching by zona thinning has no impact on the rates of positive HCG , clinical pregnancy and implantation , whereas in frozen-thawed cycles , assisted hatching by zona thinning significantly increases all three of these rates The aim of this study was to examine the safety and the efficiency of a ' non-contact ' UV laser to assist hatching through zona opening of human embryos . Between January and November 1995 we performed zona drilling for assisted hatching using a new laser system ( PALM UV Laser microbeam ) , operating in a ' non-contact ' mode to create a hole in the zona pellucida of human embryos . In a r and omized study , laser zona opening was applied on embryos from two groups of patients with repeated in-vitro fertilization ( IVF ) failures ( two to four attempts ) : group A was composed of 107 patients who received mixed embryos ( 216 laser-treated and 223 not treated ) and group B of 72 patients who received 218 laser-treated embryos only . Both groups were compared with a control group of 98 patients whose embryos were not laser treated ( n = 407 ) ( group C ) . The mean ages of all groups ( 38.1 , 38.2 and 37.8 years respectively ) and the number of IVF attempts ( two to four attempts ) were similar . The result ing clinical pregnancies were 39 ( 36.4 % ) in group A , 32 ( 44.4 % ) in group B and 19 ( 19.3 % ) in group C. The implantation rates/embryo were 9.3 % in A , 16 % in B and 5.1 % in the control group . In total , 17 normal babies have been delivered ( 10 in group A and seven in group B ) . These results show that laser zona drilling increased the pregnancy and implantation rates in all the treated patients . The increase was slight but significant in patients of group A ( P < 0.01 and P < 0.02 ) , it was even higher in the patients of group B ( P < 0.05 ) The aim of this study was to determine if laser zona thinning could improve the rates of pregnancy and implantation for vitrified-warmed embryo transfer at the cleavage stage . A total of 400 vitrified-warmed embryo transfer cycles were r and omly assigned to either the test group or the control group . The zona pellucida of vitrified-warmed embryos in the patients of the control group was untreated , whereas in the test group it was partially thinned by laser just before embryo transfer . In the test group , the clinical pregnancy and implantation rates were significantly lower as compared with that of the control group ( 28.5 versus 43.0 , P=0.002 , and 11.2 versus 16.7 , P=0.004 , respectively ) . Therefore the results of this investigation show that laser zona thinning may have an unexpected adverse effect on the rates of clinical pregnancy and implantation of vitrified-warmed embryos at the cleavage stage Observational studies have reported inconsistent results on the association between fruit and vegetable intake and the risk of pancreatic cancer . We carried out a meta- analysis of epidemiological studies to summarize available evidence . We search ed PubMed , Scopus , and ISI Web of Science data bases for relevant studies published until the end of January 2015 . Fixed-effects and r and om-effects models were used to estimate the summary relative risks ( RRs ) and 95 % confidence intervals ( CIs ) for the associations between fruit and vegetable intake and the risk of pancreatic cancer . A total of 15 case – control studies , eight prospect i ve studies , and one pooled analysis fulfilled the inclusion criteria . The summary RR for the highest versus the lowest intake was 0.73 ( 95 % CI=0.53–1.00 ) for fruit and vegetables , 0.73 ( 95 % CI=0.63–0.84 ) for fruit , and 0.76 ( 95 % CI=0.69–0.83 ) for vegetables , with significant heterogeneities ( I2=70.5 , 55.7 , and 43.0 % , respectively ) . Inverse associations were observed in the stratified analysis by study design , although the results of prospect i ve studies showed borderline significance , with corresponding RR=0.90 ( 95 % CI=0.77–1.05 ) for fruit and vegetable intake , 0.93 ( 95 % CI=0.83–1.03 ) for fruit intake , and 0.89 ( 95 % CI=0.80–1.00 ) for vegetable intake . Besides , significant inverse associations were observed in the majority of other subgroup analyses by study quality , geographic location , exposure assessment method , and adjustment for potential confounders . Findings from the present meta- analysis support that fruit and vegetable intake is associated inversely with the risk of pancreatic cancer . However , study design may play a key role in the observed magnitude of the aforementioned association . Future well- design ed prospect i ve studies are warranted to confirm these findings OBJECTIVE To determine whether a new assisted hatching ( AH ) method increases the implantation and clinical pregnancy rates of frozen-thawed day-3 ( D3 ) embryos . DESIGN Prospect i ve study . SETTING A university hospital in vitro fertilization ( IVF ) program . PATIENT(S ) Patients who had their first IVF/intracytoplasmic sperm injection ( ICSI ) cycles between June 1 , 2006 , and December 31 , 2008 , with fresh IVF-embryo transfer failures or without fresh embryo transfer . INTERVENTION(S ) The couples were r and omized into thawed embryo transfer after AH versus no AH . In the AH group , the zona pellucida ( ZP ) of D3 frozen-thawed embryos was exp and ed by injected hydrostatic pressure after thawing . In the control group , embryos were pierced by ICSI needles without exp and ing the ZP . MAIN OUTCOME MEASURE(S ) Clinical pregnancy and implantation rates . RESULT ( S ) The morphologic features of the blastomeres were carefully monitored and recorded . In the AH group , 244 embryos were thawed , and 178 ( 73.0 % ) survived ; in the control group , 259 embryos were thawed , and 190 ( 73.4 % ) survived . Despite the transfer of a similar number of embryos , the AH group result ed in statistically significantly higher implantation and clinical pregnancy rates compared with the no AH group . CONCLUSION ( S ) Mechanically exp and ing the ZP of frozen-thawed D3 embryos with injected hydrostatic pressure after thawing increases the implantation rate compared with control embryos |
11,113 | 24,712,557 | Conclusions Increases in F&V intakes were positively associated with the number of participant intervention contacts .
Dietary interventions delivered during the retirement transition are therefore effective , sustainable in the longer term and likely to be of public health significance | Background Retirement from work involves significant lifestyle changes and may represent an opportunity to promote healthier eating patterns in later life .
However , the effectiveness of dietary interventions during this period has not been evaluated . | Background Tailored nutrition interventions have been shown to be more effective than non-tailored material s in changing dietary behaviours , particularly fat intake and fruit and vegetable intake . But further research examining efficacy of tailored nutrition education in comparison to other nutrition education methods and across a wider range of dietary behaviours is needed . The Stages to Healthy Eating Patterns Study ( STEPs ) was an intervention study , in middle-aged adults with cardiovascular risk factors , to examine the effectiveness of printed , tailored , iterative dietary feedback delivered by mail in improving short-term dietary behaviour in the areas of saturated fat , fruit , vegetable and grain and cereal intake . Methods STEPs was a 3-month r and omised controlled trial with a pre and post-test design . There were three experimental conditions : 1 ) tailored , iterative , printed dietary feedback ( TF ) with three instalments mail-delivered over a 3-month period that were re-tailored to most recent assessment of dietary intake , intention to change and assessment of self-adequacy of dietary intake . Tailoring for dietary intake was performed on data from a vali date d 63-item combination FFQ design ed for the purpose 2 ) small group nutrition education sessions ( GE ) : consisting of two 90-minute dietitian-led small group nutrition education sessions and 3 ) and a wait-listed control ( C ) group who completed the dietary measures and socio-demographic question naires at baseline and 3-months later . Dietary outcome measures in the areas of saturated fat intake ( g ) , and the intake of fruit ( serves ) , vegetables ( serves ) , grain and cereals as total and wholegrain ( serves ) were collected using 7-day estimated dietary records . Descriptive statistics , paired t-tests and general linear models adjusted for baseline dietary intake , age and gender were used to examine the effectiveness of different nutrition interventions . Results The TF group reported a significantly greater increase in fruit intake ( 0.3 serves/d P = 0.031 ) in comparison to GE and the C group . All three intervention groups showed a reduction in total saturated fat intake . GE also had a within-group increase in mean vegetable intake after 3 months , but this increase was not different from changes in the other groups . Conclusions In this study , printed , tailored , iterative dietary feedback was more effective than small group nutrition education in improving the short-term fruit intake behaviour , and as effective in improving saturated fat intake of middle-aged adults with cardiovascular risk factors . This showed that a low-level dietary intervention could achieve modest dietary behaviour changes that are of public health significance Objective To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages . Design Prospect i ve cohort study . Setting The Nurses ’ Health Study , United States . Participants 17 065 women who survived until at least the age of 70 , provided information on occurrence of chronic disease , cognitive function , physical function , and mental health at older ages , and were free from major chronic diseases at mid-life ( mean age was 50 at baseline in 1976 ) . Main outcome measures Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive , physical , or mental limitations . Results Of the women who survived until at least age 70 , 1686 ( 9.9 % ) met our criteria for healthy survival . Increased body mass index ( BMI ) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival , after adjustment for various lifestyle and dietary variables ( P<0.001 for trend ) . Compared with lean women ( BMI 18.5 - 22.9 ) , obese women ( BMI ≥30 ) had 79 % lower odds of healthy survival ( odds ratio 0.21 , 95 % confidence interval 0.15 to 0.29 ) . In addition , the more weight gained from age 18 until mid-life , the less likely was healthy survival after the age of 70 . The lowest odds of healthy survival were among women who were overweight ( BMI ≥25 ) at age 18 and gained ≥10 kg weight ( 0.18 , 0.09 to 0.36 ) , relative to women who were lean ( BMI 18.5 - 22.9 ) and maintained a stable weight . Conclusions These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages , and emphasise the importance of maintaining a healthy weight from early adulthood Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression . R and omized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies . The aim of this study was to compare in a r and omized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention . Methods This was a multicenter , r and omized , primary prevention field trial of cardiovascular disease ( Prevención con Dieta Mediterránea ( PREDIMED Study ) ) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease ( 51 % of them had type 2 diabetes ; DM2 ) attending primary care centers affiliated with 11 Spanish teaching hospitals . Primary analyses were performed on an intention-to-treat basis . Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression . Results We identified 224 new cases of depression during follow-up . There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts ( multivariate hazard ratio ( HR ) 0.78 ; 95 % confidence interval ( CI ) 0.55 to 1.10 ) compared with participants assigned to the control group , although this was not significant . However , when the analysis was restricted to participants with DM2 , the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance ( multivariate HR = 0.59 ; 95 % CI 0.36 to 0.98 ) . Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2.Trial registration This trial has been registered in the Current Controlled Trials with the number IS RCT N Background The increased prevalence of overweight and obesity warrants preventive actions , particularly among people in transitional stages associated with lifestyle changes , such as occupational retirement . The purpose is to investigate the effect of a one year low-intensity computer-tailored energy balance programme among recent retirees on waist circumference , body weight and body composition , blood pressure , physical activity and dietary intake . Methods A r and omised controlled trial was conducted among recent retirees ( N = 413 ; mean age 59.5 years ) . Outcome measures were assessed using anthropometry , bio-impedance , blood pressure measurement and question naires . Results Waist circumference , body weight and blood pressure decreased significantly in men of the intervention and control group , but no significant between-group-differences were observed at 12 or at 24-months follow-up . A significant effect of the programme was only observed on waist circumference ( -1.56 cm ( 95%CI : -2.91 to -0.21 ) ) at 12 month follow up among men with low education ( n = 85 ) . Physical activity and dietary behaviours improved in both the intervention and control group during the intervention period . Although , these behaviours changed more favourably in the intervention group , these between-group-differences were not statistically significant . Conclusions The multifaceted computer-tailored programme for recent retirees did not appear to be effective . Apparently the transition to occupational retirement and /or participation in the study had a greater impact than the intervention programme . Trial registration Clinical Trials NCT00122213 OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk Background : Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers , data on overall cancer risk are sparse . Methods : We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospect i ve Investigation Into Cancer and nutrition , a multi-centre prospect i ve cohort study including 142 605 men and 335 873 . Adherence to Mediterranean diet was examined using a score ( range : 0–9 ) considering the combined intake of fruits and nuts , vegetables , legumes , cereals , lipids , fish , dairy products , meat products , and alcohol . Association with cancer incidence was assessed through Cox regression modelling , controlling for potential confounders . Results : In all , 9669 incident cancers in men and 21 062 in women were identified . A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet ( hazard ratio=0.96 , 95 % CI 0.95–0.98 ) for a two-point increment of the Mediterranean diet score . The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco ( P (heterogeneity)=0.008 ) . In all , 4.7 % of cancers among men and 2.4 % in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern . Conclusion : Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted Background Computer tailoring and motivational interviewing show promise in promoting lifestyle change , despite few head-to-head comparative studies . Purpose Vitalum is a r and omized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults . Methods Participants ( n = 1,629 ) were recruited via 23 general practice s and r and omly received either four tailored print letters , four motivational telephone calls , two of each type of intervention , or no information . The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption . Results All three intervention groups ( i.e. , the tailored letters , the motivational calls , and the combined version ) were equally and significantly more effective than the control group in increasing physical activity ( hours/day ) , intake of fruit ( servings/day ) , and consumption of vegetables ( grams/day ) from baseline to the intermediate measurement ( week 25 ) , follow-up 1 ( week 47 ) and 2 ( week 73 ) . Effect sizes ( Cohen ’s d ) ranged from 0.15 to 0.18 . Participants rated the interventions positively ; interviews were more positively evaluated than letters . Conclusions Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors BACKGROUND The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber ( 4.30 g/MJ ) , high-fruit- and -vegetable ( 0.84 servings/MJ ) , low-fat ( 20 % of energy from fat ) diet on the recurrence of adenomatous polyps in the large bowel . OBJECTIVE Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention 's effect on the intake of other food groups and nutrients . DESIGN Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were r and omly assigned to either the intervention ( n = 1037 ) or the control ( n = 1042 ) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change : food-frequency question naires ( in 100 % of the sample ) , 4-d food records ( in a 20 % r and om cohort ) , and 24-h dietary recalls ( in a 10 % r and om sample ) . RESULTS Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments ; the control participants ' intakes remained essentially the same throughout the trial . The absolute differences between the intervention and control groups over the 4-y period were 9.7 % of energy from fat ( 95 % CI : 9.0 % , 10.3 % ) , 1.65 g dietary fiber/MJ ( 95 % CI : 1.53 , 1.74 ) , and 0.27 servings of fruit and vegetables/MJ ( 95 % CI : 0.25 , 0.29 ) . Intervention participants also reported significant changes in the intake of other nutrients and food groups . The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group . CONCLUSION Motivated , free-living individuals , given appropriate support , can make and sustain major dietary changes over a 4-y period Objective To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality . Design Prospect i ve cohort study . Setting Greek segment of the European Prospect i ve Investigation into Cancer and nutrition ( EPIC ) . Participants 23 349 men and women , not previously diagnosed with cancer , coronary heart disease , or diabetes , with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment . Main outcome measure All cause mortality . Results After a mean follow-up of 8.5 years , 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0 - 4 and 423 among 10 655 participants with scores of 5 or more . Controlling for potential confounders , higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality ( adjusted mortality ratio per two unit increase in score 0.864 , 95 % confidence interval 0.802 to 0.932 ) . The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5 % , low consumption of meat and meat products 16.6 % , high vegetable consumption 16.2 % , high fruit and nut consumption 11.2 % , high monounsaturated to saturated lipid ratio 10.6 % , and high legume consumption 9.7 % . The contributions of high cereal consumption and low dairy consumption were minimal , whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio . Conclusion The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol , low consumption of meat and meat products , and high consumption of vegetables , fruits and nuts , olive oil , and legumes . Minimal contributions were found for cereals and dairy products , possibly because they are heterogeneous categories of foods with differential health effects , and for fish and seafood , the intake of which is low in this population Abstract : Breast cancer incidence and mortality rates are markedly lower in the south than in the north of Europe . This has been ascribed to differences in lifestyle and , notably , dietary habits across European countries . However , little information exists on the influence of different dietary regimens on estrogens and , hence , on breast cancer risk . Here we report results of our MeDiet Project , a r and omized , dietary intervention study aim ed to assess the effect of a Mediterranean diet on the profiles of endogenous estrogens in healthy postmenopausal women . Out of the 230 women who initially volunteered to participate in the study , 115 were found to be eligible and were enrolled . Women were then r and omly assigned into an intervention ( n = 58 ) and a control ( n = 57 ) group . Women in the intervention group adhered to a traditional , restricted Mediterranean diet for 6 mo , whereas women in the control group continued to follow their regular diet . Women in the intervention group changed their dietary regimen substantially , and this eventually led to a shift from a prevalent intake of animal fat and proteins to a prevalent intake of vegetable fat and proteins . Regarding urinary estrogens , no significant difference was observed between the intervention and control groups at baseline . After 6 mo , however , control women did not show any major change but women in the intervention group exhibited a significant decrease ( over 40 % ) of total estrogen levels ( P < 0.02 ) . The largest part of this modification was based on a marked decrease of specific estrogen metabolites , including hydroxy and keto-derivatives of estradiol or estrone . To our knowledge , this is the first report to show that a traditional Mediterranean diet significantly reduces endogenous estrogen . This may eventually lead to identify selected dietary components that more effectively decrease estrogens levels and , hence , provide a basis to develop dietary preventive measures for breast cancer OBJECTIVES This study assessed the effects of the Black Churches United for Better Health project on increasing fruit and vegetable consumption among rural African American church members in North Carolina . METHODS Ten counties comprising 50 churches were pair matched and r and omly assigned to either intervention or delayed intervention ( no program until after the follow-up survey ) conditions . A multicomponent intervention was conducted over approximately 20 months . A total of 2519 adults ( 77.3 % response rate ) completed both the baseline and 2-year follow-up interviews . RESULTS The 2 study groups consumed similar amounts of fruits and vegetables at baseline . AT the 2-year follow-up , the intervention group consumed 0.85 ( SE = 0.12 ) servings more than the delayed intervention group ( P < .0001 ) . The largest increases were observed among people 66 years or older ( 1 serving ) , those with education beyond high school ( 0.92 servings ) , those widowed or divorced ( 0.96 servings ) , and those attending church frequently ( 1.3 servings ) . The last improvement occurred among those aged 18 to 37 years and those who were single . CONCLUSIONS The project was a successful model for achieving dietary change among rural African Americans BACKGROUND Current cancer prevention recommendations include reducing consumption of fat and increasing consumption of fruits and vegetables . METHODS Healthy women health maintenance organization members ( n = 616 ) ages 40 - 70 were r and omly assigned to either a nutrition intervention or a control intervention unrelated to diet . Intervention included two 45-min counseling sessions plus two brief follow-up telephone contacts . Counseling sessions included a 20-min , interactive , computer-based intervention using a touch-screen format . Intervention goals were reducing dietary fat and increasing fruit and vegetable consumption . Outcome measures included a food frequency question naire and the Fat and Fiber Behavior Question naire ( FFBQ ) . Total serum cholesterol was also measured at baseline and 12 months . RESULTS Twelve-month follow-up data showed improvements on all dietary outcome variables . Compared to the control , intervention participants reported significantly less fat consumption ( 3.75 points less for percentage of energy from fat ) , significantly greater consumption of fruit and vegetables combined ( 0.93 more servings per day ) , and a significant reduction in a behavioral measure of fat consumption ( 0.20 point change in the FFBQ ) . Group differences in total serum cholesterol , while in the desired direction , were not significant . CONCLUSIONS In appropriate circumstances , moderate-intensity dietary interventions can show significant effects for periods of at least 1 year Purpose . This study examined how to improve dietary habits of individuals from the general public . Design . The Eating for a Healthy Life project was a r and omized trial . Setting . The study was conducted among members of religious organizations ( ROs ) . Subjects . Participants were a sample of RO members . Intervention . The intervention was a multilevel package , based on our previous experience , design ed to lower fat and increase fruit and vegetable consumption . Measures . The Eating Behaviors Question naire was administered preintervention and postintervention , together with 24-hour food recalls in a r and omly selected subset . Analysis . Linear mixed models were used to evaluate the study 's intervention , incorporating the design effects of blocking , intraclass correlation within RO , and correlation between the preintervention and postintervention points . Results . Participants ( n = 2175 ) reported significantly healthier dietary behaviors in intervention ROs at the 12-month follow-up period , compared to participants in the comparison ROs , for a fat scale change of .08 summary scale points and an adjusted intervention effect of .06 overall . Conclusion . Dietary intervention through ROs is a positive and successful method of changing dietary habits OBJECTIVE To study changes in lifestyle in relation to changes in body weight and waist circumference associated with occupational retirement in men . DESIGN A prospect i ve cohort study with 5 years of follow-up . At baseline and at follow-up , question naires were completed and body weight and waist circumference were measured . SETTING The Doetinchem Cohort Study , consisting of inhabitants of Doetinchem , a town in a rural area of The Netherl and s. SUBJECTS In total 288 healthy men aged 50 - 65 years at baseline , who either remained employed or retired over follow-up . RESULTS The effect of retirement on changes in weight and waist circumference was dependent on type of former occupation . Increase in body weight and waist circumference was higher among men who retired from active jobs ( 0.42 kg year(-1 ) and 0.77 cm year(-1 ) , respectively ) than among men who retired from sedentary jobs ( 0.08 kg year(-1 ) and 0.23 cm year(-1 ) , respectively ) . Weight gain and increase in waist circumference were associated with a decrease in fruit consumption and fibre density of the diet , with an increase in frequency of eating breakfast , and with a decrease in several physical activities , such as household activities , bicycling , walking and doing odd jobs . CONCLUSION Retirement was associated with an increase in weight and waist circumference among those with former active jobs , but not among those with former sedentary jobs . Retirement may bring opportunities for healthy changes in diet and physical activity , which could be used in health promotion programmes BACKGROUND High dietary intakes of fruit and vegetables are associated with reduced risks of cancer and cardiovascular disease . Short-term intensive dietary interventions in selected population s increase fruit and vegetable intake , raise plasma antioxidant concentrations , and lower blood pressure , but long-term effects of interventions in the general population are not certain . We assessed the effect of an intervention to increase fruit and vegetable consumption on plasma concentrations of antioxidant vitamins , daily fruit and vegetable intake , and blood pressure . METHODS We undertook a 6-month , r and omised , controlled trial of a brief negotiation method to encourage an increase in consumption of fruit and vegetables to at least five daily portions . We included 690 healthy participants aged 25 - 64 years recruited from a primary -care health centre . FINDINGS Plasma concentrations of alpha-carotene , beta-carotene , lutein , beta-cryptoxanthin , and ascorbic acid increased by more in the intervention group than in controls ( significance of between-group differences ranged from p=0.032 to 0.0002 ) . Groups did not differ for changes in lycopene , retinol , alpha-tocopherol , gamma-tocopherol , or total cholesterol concentrations . Self-reported fruit and vegetable intake increased by a mean 1.4 ( SD 1.7 ) portions in the intervention group and by 0.1 ( 1.3 ) portion in the control group ( between-group difference=1.4 , 95 % CI 1.2 - 1.6 ; p<0.0001 ) . Systolic blood pressure fell more in the intervention group than in controls ( difference=4.0 mm Hg , 2.0 - 6.0 ; p<0.0001 ) , as did diastolic blood pressure ( 1.5 mm Hg , 0.2 - 2.7 ; p=0.02 ) . INTERPRETATION The effects of the intervention on fruit and vegetable consumption , plasma antioxidants , and blood pressure would be expected to reduce cardiovascular disease in the general population OBJECTIVE This study examines the extent to which a plant-based dietary intervention that discourages consumption of dairy products and meat influences bone-relevant nutrients . METHODS A r and omized controlled study design was used to evaluate the Coronary Health Improvement Project . The Project is a heart disease prevention intervention administered in an intensive 40-hour educational course delivered over a 4-week period . Participants were evaluated at baseline , 6 weeks , and 6 months . RESULTS After 6 weeks , participants in the intervention group compared with the control group experienced significant increases in magnesium and daily intake of fruit , vegetables , and grains but significant decreases in dairy servings per day and calcium and vitamin D from food . After 6 months , those in the intervention group showed significant increases in daily intake of fruit , vegetables , and grains and significant decreases in dairy servings per day , daily meat consumption , and protein , phosphorous , calcium , total calcium , and vitamin D from food . Serum calcium levels are the primary determinant of parathyroid hormone ( PTH ) release , and within 6 weeks , the intervention group 's PTH levels were elevated from baseline and significantly different from the control group 's PTH levels . At 6 months , urinary type I collagen N-telopeptide ( NTx ) levels were significantly greater in the intervention group compared with the control group . CONCLUSIONS The Coronary Health Improvement Project increases the intake of important food items but decreases calcium and vitamin D consumption . There is also some evidence of an increase in NTx biomarkers , consistent with increased bone resorption This r and omized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse background s. During 1992 - 1994 , 2,208 women aged 50 - 79 years , 28 % of whom were black and 16 % Hispanic , enrolled at clinics in Atlanta , Georgia , Birmingham , Alabama , and Miami , Florida . Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20 % of energy and to make other diet modifications . At 6 months postr and omization , the intervention group reduced fat intake from 39.7 % of energy at baseline to 26.4 % , a reduction of 13.3 % of energy , compared with 2.3 % among controls . Saturated fatty acid and cholesterol intakes were reduced , but intakes of fruits and vegetables , but not grain products , increased . Similar effects were observed at 12 and 18 months . Black and non-Hispanic white women had similar levels of reduction in fat , but the decrease in Hispanic women was less . Changes did not vary significantly by education . While bias in self-reported intakes may have result ed in somewhat overestimated changes in fat intake , the reported reduction was similar to the approximately 10 % of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study population s and in many subgroups OBJECTIVE To investigate the impact of intensive group education on the Mediterranean diet on dietary intake and serum total cholesterol after 16 and 52 weeks , compared to a posted leaflet with the Dutch nutritional guidelines , in the context of primary prevention of cardiovascular disease ( CVD ) . DESIGN Controlled comparison study of an intervention group given intensive group education about the Mediterranean diet and a control group of hypercholesterolaemic persons given usual care by general practitioners ( GPs ) . SETTING A socioeconomically deprived area in the Netherl and s with an elevated coronary heart disease ( CHD ) mortality ratio . SUBJECTS Two hundred and sixty-six hypercholesterolaemic persons with at least two other CVD risk factors . RESULTS After 52 weeks , the intervention group decreased total and saturated fat intake more than the control group ( net differences were 1.8 en% ( 95%CI 0.2 - 3.4 ) and 1.1 en% ( 95%CI 0 . 4 - 1.9 ) , respectively ) . According to the Mediterranean diet guidelines the intake of fish , fruit , poultry and bread increased in the intervention group , more than in the control group . Within the intervention group , intake of fish ( + 100 % ) , poultry ( + 28 % ) and bread ( + 6 % ) was significantly increased after 1 year ( P < 0.05 ) . The intensive programme on dietary education did not significantly lower serum cholesterol level more ( -3 % ) than the posted leaflet ( -2 % ) ( net difference 0.06 mmol l-1 , 95%CI -0.10 to 0.22 ) . Initially , the body mass index ( BMI ) decreased more in the intervention group , but after 1 year the intervention and control group gained weight equally ( + 1 % ) . CONCLUSIONS Despite beneficial changes in dietary habits in the intervention group compared with the control group , after 1 year BMI increased and total fat and saturated fat intake were still too high AIMS A higher intake of fruits and vegetables has been associated with a lower risk of ischaemic heart disease ( IHD ) , but there is some uncertainty about the interpretation of this association . The objective was to assess the relation between fruit and vegetable intake and risk of mortality from IHD in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Heart study . METHODS AND RESULTS After an average of 8.4 years of follow-up , there were 1636 deaths from IHD among 313 074 men and women without previous myocardial infa rct ion or stroke from eight European countries . Participants consuming at least eight portions ( 80 g each ) of fruits and vegetables a day had a 22 % lower risk of fatal IHD [ relative risk ( RR ) = 0.78 , 95 % confidence interval ( CI ) : 0.65 - 0.95 ] compared with those consuming fewer than three portions a day . After calibration of fruit and vegetable intake to account for differences in dietary assessment between the participating centres , a one portion ( 80 g ) increment in fruit and vegetable intake was associated with a 4 % lower risk of fatal IHD ( RR = 0.96 , 95 % CI : 0.92 - 1.00 , P for trend = 0.033 ) . CONCLUSION Results from this large observational study suggest that a higher intake of fruits and vegetables is associated with a reduced risk of IHD mortality . Whether this association is causal and , if so , the biological mechanism(s ) by which fruits and vegetables operate to lower IHD risks remains unclear Background : Unhealthy diet and lack of physical activity increase rural midlife and older women 's risk of chronic diseases and premature death , and they are behind urban residents in meeting Healthy People 2010 objectives . Objectives : The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women . Methods : In a r and omized-by-site , community-based , controlled , clinical trial , Wellness for Women , 225 women aged 50 to 69 years were recruited in two similar rural areas . Over 12 months , women received by mail either 18 generic newsletters or 18 newsletters computer tailored on Health Promotion Model behavior-specific cognitions ( benefits , barriers , self-efficacy , and interpersonal support ) , activity , and eating . Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating . Data were analyzed by repeated- measures analysis of variance and chi-square tests ( & agr ; < .05 ) . Results : Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased percentage of calories from fat , whereas only the tailored group increased moderate or greater intensity activity and decreased percentage of calories from saturated fat from baseline to 6 months . Both groups increased stretching and strengthening exercise , whereas only the tailored group increased moderate or greater intensity activity and fruit and vegetable servings and decreased percentage of calories from fat from baseline to 12 months . Both groups had several changes in biomarkers over the study . A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for moderate or greater intensity activity , fruit and vegetable servings , and percentage of calories from fat at 12 months . Discussion : Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months . Tailored newsletters were more efficacious in facilitating change over 12 months Background / Objectives : To compare the effects of two dietary approaches on changes in dietary intakes and body weight : ( 1 ) an approach emphasizing nonrestrictive messages directed toward the inclusion of fruits and vegetables ( HIFV ) and ( 2 ) another approach using restrictive messages to limit high-fat foods (LOFAT).Subjects/ Methods : A total of 68 overweight – obese postmenopausal women were r and omly assigned to one of the two dietary approaches . The 6-month dietary intervention included three group sessions and ten individual sessions with a dietitian . Dietary food intake and anthropometric variables were measured at baseline , at 3 months and at 6 months . Results : Energy density decreased in both groups after the intervention compared with baseline ( HIFV , −0.3±0.2 kcal/g ; LOFAT , −0.3±0.3 kcal/g ; P<0.0001 ) . Although body weight decreased significantly in both groups after the intervention compared with baseline ( HIFV , −1.6±2.9 kg ; LOFAT , −3.5±2.9 kg ; P<0.0001 ) , women in the LOFAT group lost significantly more body weight than women in the HIFV group ( P=0.01 ) . In the HIFV group , the decrease in energy density was found to be an independent predictor of body weight loss . Conclusions : The LOFAT approach induces more weight loss than does the HIFV approach in our sample of overweight – obese postmenopausal women BACKGROUND Results are reported from a large r and omized trial design ed to increase fruit and vegetable consumption among callers to the National Cancer Institute 's Cancer Information Service ( CIS ) ( n = 1,717 ) . METHODS CIS callers assigned to the intervention group ( n = 861 ) received a brief proactive educational intervention over the telephone at the end of usual service , with two follow-up mailouts . Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants . Participants were interviewed by telephone at 4 weeks ( n = 1,307 ) , 4 months ( n = 1,180 ) , and 12 months for follow-up ( n = 1,016 ) . RESULTS Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up ( P < 0.001 ) , 0.63 servings per day at 4 months follow-up ( P < 0.001 ) , and 0.43 servings per day at 12 months follow-up ( P < 0.001 ) . Using a 7-item food frequency measure , an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up ( P < 0.001 ) , compared with 0.39 servings per day at 4 months follow-up ( P = 0.002 ) and 0.44 servings per day at 12 months follow-up ( P = 0.002 ) . A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day ( P = 0.015 ) . The vast majority of callers ( 90 % ) endorsed the strategy of providing 5 A Day information proactively within the CIS . CONCLUSIONS This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term follow-up . Additional research is recommended to test this or a similar intervention in diverse population Objective Previous observational studies reported beneficial effects of the Mediterranean diet ( MedDiet ) on cognitive function , but results were inconsistent . We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet . Methods We assessed 522 participants at high vascular risk ( 44.6 % men , age 74.6 ± 5.7 years at cognitive evaluation ) enrolled in a multicentre , r and omised , primary prevention trial ( PREDIMED ) , after a nutritional intervention comparing two MedDiets ( supplemented with either extra-virgin olive oil ( EVOO ) or mixed nuts ) versus a low-fat control diet . Global cognitive performance was examined by Mini-Mental State Examination ( MMSE ) and Clock Drawing Test ( CDT ) after 6.5 years of nutritional intervention . Research ers who assessed the outcome were blinded to group assignment . We used general linear models to control for potential confounding . Results After adjustment for sex , age , education , Apolipoprotein E genotype , family history of cognitive impairment/dementia , smoking , physical activity , body mass index , hypertension , dyslipidaemia , diabetes , alcohol and total energy intake , participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control ( adjusted differences : + 0.62 95 % CI + 0.18 to + 1.05 , p=0.005 for MMSE , and + 0.51 95 % CI + 0.20 to + 0.82 , p=0.001 for CDT ) . The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control ( adjusted differences : + 0.57 ( 95 % CI + 0.11 to + 1.03 ) , p=0.015 for MMSE and + 0.33 ( 95 % CI + 0.003 to + 0.67 ) , p=0.048 for CDT ) . These results did not differ after controlling for incident depression . Conclusions An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet . IS RCT BACKGROUND Fruit and vegetable ( FV ) intake in black men are far below national recommendations . METHODS Urban , primarily immigrant , black men ( n=490 ) from the New York City metropolitan area participating in the Cancer Awareness and Prevention ( CAP ) Trial ( 2005 - 2007 ) were r and omly assigned to one of two intervention groups : 1 ) FV Education ( FVE ) or 2 ) Prostate Education ( PE ) . Both interventions entailed a mailed brochure plus two tailored telephone education ( TTE ) calls . Outcomes , measured at baseline and at eight months , included knowledge of FV recommendations , perceived benefits , stage of readiness to adopt recommendations and self-reported FV consumption . RESULTS At follow-up , the FVE group consumed an average of 1.2 more FV servings per day than the PE group ( P<0.001 ; adjusted for baseline ) . The FVE group also demonstrated increases in knowledge about recommended FV amounts ( P<0.01 ) and appropriate serving sizes ( P<0.05 ) , and in the percent of participants moving from a lower to a higher stage of readiness to adopt FV recommendations ( P<0.05 ) . The FVE group did not demonstrate increases in knowledge related to the importance of eating a colorful variety or in the ability to name potential health benefits . CONCLUSIONS TTE can be a practical and moderately effective intervention for raising awareness of FV recommendations and for promoting FV consumption in urban and primarily immigrant black men OBJECTIVE To assess the effectiveness of an intervention aim ed to increase adherence to a Mediterranean diet . DESIGN A 12-month assessment of a r and omized primary prevention trial . SUBJECTS/ SETTING S One thous and five hundred fifty-one asymptomatic persons aged 55 to 80 years , with diabetes or > or =3 cardiovascular risk factors . INTERVENTION Participants were r and omly assigned to a control group or two Mediterranean diet groups . Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals , and group educational sessions on a quarterly basis . One Mediterranean diet group received free virgin olive oil ( 1 L/week ) , the other received free mixed nuts ( 30 g/day ) . Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines . MAIN OUTCOME MEASURES Changes in food and nutrient intake after 12 months . STATISTICAL ANALYSES Paired t tests ( for within-group changes ) and analysis of variance ( for between-group changes ) were conducted . RESULTS Participants allocated to both Mediterranean diets increased their intake of virgin olive oil , nuts , vegetables , legumes , and fruits ( P<0.05 for all within- and between-group differences ) . Participants in all three groups decreased their intake of meat and pastries , cakes , and sweets ( P<0.05 for all ) . Fiber , monounsaturated fatty acid , and polyunsaturated fatty acid intake increased in the Mediterranean diet groups ( P<0.005 for all ) . Favorable , although nonsignificant , changes in intake of other nutrients occurred only in the Mediterranean diet groups . CONCLUSIONS A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individual 's overall food pattern . The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial BACKGROUND Ascorbic acid ( vitamin C ) might be protective for several chronic diseases . However , findings from prospect i ve studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent . We aim ed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes , cardiovascular disease , ischaemic heart disease , and cancer . METHODS We prospect ively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes , and to cardiovascular disease , ischaemic heart disease , and cancer in 19 496 men and women aged 45 - 79 years . We recruited individuals by post using age-sex registers of general practice s. Participants completed a health and lifestyle question naire and were examined at a clinic visit . They were followed-up for causes of death for about 4 years . Individuals were divided into sex-specific quintiles of plasma ascorbic acid . We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality . FINDINGS Plasma ascorbic acid concentration was inversely related to mortality from all-causes , and from cardiovascular disease , and ischaemic heart disease in men and women . Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile ( p<0.0001 ) . The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations . 20 micromol/L rise in plasma ascorbic acid concentration , equivalent to about 50 g per day increase in fruit and vegetable intake , was associated with about a 20 % reduction in risk of all-cause mortality ( p<0.0001 ) , independent of age , systolic blood pressure , blood cholesterol , cigarette smoking habit , diabetes , and supplement use . Ascorbic acid was inversely related to cancer mortality in men but not women . INTERPRETATION Small increases in fruit and vegetable intake of about one serving daily has encouraging prospect s for possible prevention of disease Objective To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels . Design Open r and omised , controlled trial . Setting Free-living healthy subjects in two rural villages in north-eastern Japan . Participants Five hundred and fifty healthy volunteers aged 40–69 years . Interventions Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene , and of fruit and vegetables . Main outcome measures Blood pressure , dietary intake and urinary excretion of sodium , dietary carotene and vitamin C , and fruit and vegetable intake data were collected at 1 year after the start of the intervention . Results During the first year , changes differed significantly between the intervention and control groups for dietary ( P = 0.002 ) and urinary excretion ( P < 0.001 ) of sodium and dietary vitamin C and carotene ( P = 0.003 ) . Systolic blood pressure decreased from 127.9 to 125.2 mmHg ( 2.7 mmHg decrease ; 95 % confidence interval , −4.6 to −0.8 ) in the intervention group , whereas it increased from 128.0 to 128.5 mmHg ( 0.5 increase ; −1.3 to 2.3 ) in the control group . This change was statistically significant ( P = 0.007 ) . In contrast , the change in diastolic blood pressure did not significantly differ between the groups . In hypertensive subjects , a significant difference in systolic blood pressure reduction was seen between the groups ( P = 0.032 ) . Conclusion Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes , which result ed in a significant decrease in systolic blood pressure OBJECTIVES We evaluated a community-based , translational lifestyle program to reduce diabetes risk in lower-socioeconomic status ( SES ) and ethnic minority adults . METHODS Through an academic-public health department partnership , community-dwelling adults at risk for diabetes were r and omly assigned to individualized lifestyle counseling delivered primarily via telephone by health department counselors or a wait-list control group . Primary outcomes ( 6 and 12 months ) were fasting glucose level , triglycerides , high- and low-density lipoprotein cholesterol , weight , waist circumference , and systolic blood pressure . Secondary outcomes included diet , physical activity , and health-related quality of life . RESULTS Of the 230 participants , study retention was 92 % . The 6-month group differences for weight and triglycerides were significant . The intervention group lost 2 pounds more than did the control group ( P=.03 ) and had decreased triglyceride levels ( difference in change , 23 mg/dL ; P=.02 ) . At 6 months , the intervention group consumed 7.7 fewer grams per day of fat ( P=.05 ) and more fruits and vegetables ( P=.02 ) than did control participants . CONCLUSIONS Despite challenges design ing effective translational interventions for lower-SES and minority communities , this program modestly improved some diabetes risk factors . Thus , individualized , telephone-based models may be a promising alternative to group-based interventions BACKGROUND The Next Step Trial tested interventions encouraging prevention and early detection practice s in automotive-industry employees at increased colorectal cancer risk . This article describes results of the nutrition intervention promoting low-fat , high-fiber eating patterns . METHODS Twenty-eight worksites ( 5,042 employees at baseline ) were r and omized to a 2-year nutrition intervention including classes , mailed self-help material s , and personalized dietary feedback . Control worksites received no intervention . Nutrition outcomes were assessed by mailed food frequency question naires ( FFQs ) Primary nutrition outcomes included percentage energy from fat and fiber density ( g/1,000 kcal ) at 1 year postr and omization . Secondary outcomes included servings of fruits/vegetables and dietary measures at 2 years postr and omization . Analyses were adjusted for within worksite correlations and baseline covariates . Fifty-eight percent of employees returned FFQs . RESULTS At 1 year , there were modest but statistically significant intervention effects for fat ( -0.9 % en ) , fiber ( + 0.5 g/1,000 kcal ) , and fruits/vegetables ( + 0.2 servings/day ) ( all P < 0.007 ) . At 2 years , due to significant positive changes in control worksites , intervention effects were smaller , significant for fiber only . Intervention effects were larger in younger ( < 50 years ) , active employees and class attendees . CONCLUSION The nutrition intervention produced significant but modest effects on dietary fat and fiber and fruits/vegetables in these high-risk employees . Age and dose effects suggest younger employees may be more responsive to this intervention The role of nutrition in preventing peripheral artery disease ( PAD ) remains elusive.1 Mediterranean diets reduce the risk of myocardial infa rct ion and stroke.2,3 They also may reduce the risk of PAD , but this hypothesis has never been tested in a r and omized trial . We assessed the association of Mediterranean diets with the occurrence of symptomatic PAD in an exploratory , nonprespecified analysis of a r and omized trial BACKGROUND Faith-based interventions hold promise for promoting health in ethnic minority population s. To date , however , few of these interventions have used a community-based participatory research ( CBPR ) approach , have targeted both physical activity and healthy eating , and have focused on structural changes in the church . PURPOSE To report the results of a group r and omized CBPR intervention targeting physical activity and healthy eating in African-American churches . DESIGN Group RCT . Data were collected from 2007 to 2011 . Statistical analyses were conducted in 2012 . SETTING / PARTICIPANTS Seventy-four African Method ist Episcopal ( AME ) churches in South Carolina and 1257 members within them participated in the study . INTERVENTION Churches were r and omized to an immediate ( intervention ) or delayed ( control ) 15-month intervention that targeted organizational and environmental changes consistent with the structural ecologic model . A CBPR approach guided intervention development . Intervention churches attended a full-day committee training and a full-day cook training . They also received a stipend and 15 months of mailings and technical assistance calls to support intervention implementation . MAIN OUTCOME MEASURES Primary outcomes were self-reported moderate- to vigorous-intensity physical activity ( MVPA ) , self-reported fruit and vegetable consumption , and measured blood pressure . Secondary outcomes were self-reported fat- and fiber-related behaviors . Measurements were taken at baseline and 15 months . Intent-to-treat repeated measures ANOVA tested group X time interactions , controlling for church clustering , wave , and size , and participant age , gender , and education . Post hoc ANCOVAs were conducted with measurement completers . RESULTS There was a significant effect favoring the intervention group in self-reported leisure-time MVPA ( d=0.18 , p=0.02 ) , but no effect for other outcomes . ANCOVA analyses showed an intervention effect for self-reported leisure-time MVPA ( d=0.17 , p=0.03 ) and self-reported fruit and vegetable consumption ( d=0.17 , p=0.03 ) . Trainings were evaluated very positively ( training evaluation item means of 4.2 - 4.8 on a 5-point scale ) . CONCLUSIONS This faith-based structural intervention using a CBPR framework showed small but significant increases in self-reported leisure-time MVPA . This program has potential for broad-based dissemination and reach . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00379925 Abstract Objective To assess the effect of brief interventions during the “ watchful waiting ” period for hypertension . Design Factorial trial . Setting General practice . Methods 296 patients with blood pressure > 160/90 mm Hg were r and omised to eight groups defined by three factors : an information booklet ; low sodium , high potassium salt ; prompt sheets for high fruit , vegetable , fibre ; and low fat . Main outcome measures Blood pressure ( primary outcome ) ; secondary outcomes of diet , weight , and dietary biomarkers ( urinary sodium : potassium ( Na : K ) ratio ; carotenoid concentrations ) . Results Blood pressure was not affected by the booklet ( mean difference ( diastolic blood pressure ) at one month 0.2 , 95 % confidence interval 1.6 to 2.0 ) , salt ( 0.13 ; 1.7 to 2.0 ) , or prompts ( 0.52 ; 1.3 to 2.4 ) . The salt decreased Na : K ratio ( difference 0.32 ; 0.08 to 0.56 , P = 0.01 ) , and the prompts helped control weight ( difference 0.39 ( 0.85 to 0.05 ) kg at one month , P = 0.085 ; 1.2 ( 0.1 to 2.25 ) kg at six months , P = 0.03 ) . Among those with lower fruit and vegetable consumption ( < 300 g per day ) , prompts increased fruit and vegetable consumption and also carotenoid concentrations ( difference 143 ( 16 to 269 ) mmol/l , P < 0.03 ) but did not decrease blood pressure . Conclusion During watchful waiting , over and above the effect of brief advice and monitoring , an information booklet , lifestyle prompts , and low sodium salt do not reduce blood pressure . Secondary analysis suggests that brief interventions —particularly lifestyle prompts — can make useful changes in diet and help control weight , which previous research indicates are likely to reduce the long term risk of stroke |
11,114 | 20,019,321 | Interventions aim ed at increasing breastfeeding , medication adherence , women 's health screening , and participation in general activities did not produce significant changes | null | null |
11,115 | 27,563,376 | Even from an early stage , imbalance in redox status is evident and as the kidney function worsens it becomes more profound .
Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers , protein carbonylation , and impairing erythrocyte antioxidant defense .
However , other dialysis modalities do not so far appear to confer advantages .
Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD | Patients with chronic kidney disease ( CKD ) experience imbalance between oxygen reactive species ( ROS ) production and antioxidant defenses leading to cell and tissue damage .
However , it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound .
The aim of this systematic review was to provide an up date on recent advances in our underst and ing of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance . | BACKGROUND Neutrophil oxygen radical production is increased in end-stage renal disease ( ESRD ) patients and it is further enhanced during dialysis with low-flux cellulosic membranes . This increased oxygen radical production may contribute to the protein and lipid oxidation observed in ESRD patients . We tested the hypothesis that high-flux hemodialysis does not increase oxygen radical production and that it is not associated with protein oxidation . METHODS Neutrophil oxygen radical production was measured during dialysis with high-flux dialyzers containing polysulfone and cellulose triacetate membranes . Free sulfhydryl and carbonyl groups and advanced oxidation protein products were measured to assess plasma protein oxidation . RESULTS Pre-dialysis , neutrophil oxygen radical production was significantly greater than normal and increased significantly as blood passed through the dialyzer in the first 30 minutes of dialysis . Post-dialysis , however , neutrophil oxygen radical production had decreased and was not different from normal . Pre-dialysis , significant plasma protein oxidation was evident from reduced free sulfhydryl groups , increased carbonyl groups , and increased advanced oxidation protein products . Post-dialysis , plasma protein free sulfhydryl groups had increased to normal levels , while plasma protein carbonyl groups increased slightly , and advanced oxidation protein products remained unchanged . CONCLUSIONS The results of this study show that neutrophil oxygen radical production normalizes during high-flux dialysis , despite a transient increase early in dialysis . This decrease in oxygen radical production is associated with an improvement in some , but not all , measures of protein oxidation Red blood cells and plasma reduced and oxidized glutathione levels , glutathione peroxidase ( GSH-Px ) activity , thiobarbituric acid reactants ( TBAR ) of both chronic ambulatory peritoneal dialysis ( CAPD ) patients and a matched control group were investigated in this study . Oxidized and reduced pyridinic nucleotides in red blood cells ( RBC ) , in which NADPH is a direct expression of hexose monophosphate shunt function , were also studied . The results obtained indicate that RBC and plasma are exposed to oxidative stress in CAPD . This condition is characterized by a decreased GSH/GSSG ratio , particularly evident in RBC as a consequence of the GSSG accumulation . Lipid peroxidation is increased , as indicated by raised TBAR levels , and reduced pyridinic nucleotides are decreased . Increased GSH-Px levels and unmodified or slightly increased GSH content were observed in the RBC but not in plasma , which showed decreased GSH and unmodified peroxidase activity . Peroxidase correlated positively with TBAR levels in the RBC lysates . In a subgroup of patients treated with erythropoietin ( vs. untreated patients and controls ) no differences were observed in the glutathione-related parameters studied . These data suggest that a mechanism for adaptation to oxidative conditions may be present in CAPD and its effects on RBC integrity are discussed in comparison with the hemodialysis conditions previously studied Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy ( MHD ) , and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness . No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress . We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients . In total , 353 patients were enrolled in a prospect i ve , placebo-controlled , double-blind clinical trial and r and omly assigned to receive a combination of mixed tocopherols ( 666 IU/d ) plus α-lipoic acid ( ALA ; 600 mg/d ) or matching placebos for 6 months ( NCT00237718 ) ; 238 patients completed the study . High-sensitivity C-reactive protein ( hsCRP ) and IL-6 concentration were measured as biomarkers of systemic inflammation , and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress . The groups did not significantly differ at baseline . At 3 and 6 months , the treatment had no significant effect on plasma hsCRP , IL-6 , F2 isoprostane , or isofuran concentrations and did not improve the erythropoietic response . No major adverse events were related to the study drug , and both groups had similar mortality and hospitalization rates during the study . In conclusion , the administration of mixed tocopherols and ALA was generally safe and well tolerated , but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response BACKGROUND Erythrocytes represent an important component of the antioxidant capacity of blood , comprising , in particular , intracellular enzymes , including platelet-activating factor acetylhydrolase ( PAF-AH ) and glutathione peroxidase ( Gpx ) . We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease ( CKD ) , and further investigated whether erythropoietin ( EPO ) administration in these patients has any influence on the enzyme activities . METHODS Thirty-six patients ( 19 men and 17 women ) with CKD ( stages 1 to 5 ) participated in the study . Thirteen of them presented with CKD stage 1 to 2 ( group I ) , whereas 23 patients presented with CKD stage 3 to 5 and r and omized into two groups ( i.e. , groups II and III ) . Patients of group II ( N= 11 ) were administered EPO subcutaneously , 50 units per kg once per week . In group III ( N= 12 ) , EPO was initiated only when the hemoglobin ( Hb ) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months . Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls . The PAF-AH and Gpx activities were determined in isolated washed erythrocytes . RESULTS The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls , the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied population s , both enzyme activities were negatively correlated with the creatinine clearance values . Importantly , the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO ( group III ) , a phenomenon not observed in patients receiving EPO ( group II ) , or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III . CONCLUSION Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients . Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency , thus preserving the erythrocyte defense mechanisms against oxidative stress BACKGROUND Lipid peroxidation may be important in the pathogenesis of atherosclerosis , particularly in its earliest stages . Evidence predominantly from in vitro studies suggests that antioxidant vitamins can prevent lipid peroxidation and that vitamin C and vitamin E have synergistic effects . However , in vivo evidence in support of these hypotheses is sparse . OBJECTIVE The objective was to determine the effects of vitamin C and vitamin E , alone or in combination , on in vivo lipid peroxidation . DESIGN We conducted a placebo-controlled , 2 x 2 factorial trial of vitamin C ( 500 mg ascorbate/d ) and vitamin E ( 400 IU RRR-alpha-tocopheryl acetate/d ) supplementation in 184 nonsmokers . The mean duration of supplementation was 2 mo . The outcome measures were changes from baseline in urinary 8-iso-prostagl and in F(2alpha ) , urinary malondialdehyde + 4-hydroxyalkenals , and serum oxygen-radical absorbance capacity . RESULTS The within-group mean changes ( and 95 % CIs ) in urinary 8-iso-prostagl and in F(2alpha ) ( pg/mg creatinine ) were 9.0 ( -125.1 , 143.1 ) , -150.0 ( -275.4 , -24.6 ) , -141.3 ( -230.5 , -52.1 ) , and -112.5 ( -234.8 , 9.8 ) in the placebo , vitamin C alone , vitamin E alone , and vitamins C + E groups , respectively . No synergistic effect of these 2 vitamins on urinary 8-iso-prostagl and in F(2alpha ) was observed ( P = 0.12 ) . Neither vitamin had an effect on urinary malondialdehyde + 4-hydroxyalkenals . Vitamin C , but not vitamin E , increased serum oxygen-radical absorbance capacity ( P = 0.01 ) . CONCLUSIONS Supplementation with vitamin C or vitamin E alone reduced lipid peroxidation to a similar extent . Supplementation with a combination of vitamins C and E conferred no benefit beyond that of either vitamin alone It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants ( particularly for the reduction of the risk of heart disease ) . The aim of this study was , first , to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and , second , to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis . Forty-one patients with end-stage renal disease were enrolled and r and omized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis . We measured lipid profile and the susceptibility of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) to oxidation using copper ions at the moment of inclusion and after 1 year . All lipoperoxidation parameters were included . Hemodialysis by itself improved the lipid profile , lowering total cholesterol ( 176.4 + /- 48.4 to 154.2 + /- 28.8 mg/dL , P < .01 ) , LDL cholesterol ( 94.1 + /- 39.6 to 76.1 + /- 26.6 mg/dL LDL , P < .03 ) , and phospholipids levels ( 196.5 + /- 36.7 to 182.9 + /- 36.1 mg/dL , P < .05 ) in all patients on maintenance hemodialysis . The HDL cholesterol was also decreased ( 49.4 + /- 19.8 to 43.4 + /- 24.1 mg/dL HDL , P < .03 ) . No significant differences were detected between patients receiving vitamin C and those receiving placebo . Thiobarbituric acid reactive substances ( TBARS ) and lipoperoxides increased in patients after a year of hemodialysis , but the difference was lower in those administered vitamin C for a year-TBARS LDL ( in nanograms per gram LDL ) : 0.25 + /- 0.20 to 0.38 + /- 0.2 in vitamin C-treated subjects and 0.28 + /- 0.17 to 0.46 + /- 0.21 in those treated with placebo ( P < .007 ) ; TBARS HDL ( in nanograms per gram HDL ) : 0.22 + /- 0.12 to 0.34 + /- 0.30 in patients receiving vitamin C and 0.20 + /- 0.18 to 0.28 + /- 0.19 in those receiving placebo ( P = .071 ) . Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia . Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients , and despite the small number of patients , the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters . This area remains controversial and under active investigation . Further research is necessary before a firm conclusion can be reached In the last few years haemodiafiltration with on-line regeneration of ultrafiltrate ( HFR ) has been shown to have a positive impact on inflammation and oxidative stress biomarkers , but its effect on antioxidant levels and on oxidative damage to biomolecules in the long-term is still unknown . This is a r and omised clinical study over 12 months involving 40 patients on haemodialysis , comparing the effect of HFR ( n = 25 ) dialysis with haemodialysis with polysulfone ( HD-PS , n = 15 ) on oxidative stress . Total antioxidant capacity , enzymatic antioxidant [ superoxide dismutase ( SOD ) , catalase and glutathione peroxidase ] , non-enzymatic ( GSH ) and biomarkers of oxidative stress ( TBARs , carbonyl groups and 8-OH-dG ) were evaluated . The antioxidant activity decreased in the lymphocytes of patients dialysed with HFR , with a significant decrease in the enzyme SOD . In the oxidative stress biomarkers , an increase was seen in the levels of 8-OH-dG in patients on HD-PS dialysis but not in those treated with HFR . Throughout the year the changes in antioxidant levels and biomarkers of oxidative damage in patients dialysed with HFR were generally more modest and fluctuated less than those dialysed with HD-PS . Our study indicates that , in general , long-term dialysis with HFR does not modified antioxidant parameters or increases the oxidative damage to biomolecules . The HFR showed to be a biocompatible technique for long-term dialysis In hemodialysis patients , oxidative stress results from an imbalance between the production of reactive oxygen species and antioxidant defense mechanisms . Recently , a new dialysis multi‐‐layer membrane has been developed , by modifying the inner surface of regenerated cellulose to support a vitamin E coating . The aim of our study was to investigate the effects of hemodialysis treatment with vitamin E‐‐modified membrane on anemia and erythropoietin requirement in a group of chronic uremic patients . Ten uremic , non diabetic , patients on st and ard bicarbonate dialysis were treated with vitamin E‐‐bonded dialysis membrane for 12 months . Hematological parameters , erythropoietin requirement , serum vitamin E and serum malonyldialdehyde ( ( MDA ) ) were evaluated before starting the study and monthly . No significant changes in hemoglobin level , RBC count , hematocrit and EPO requirement were observed . Basal vitamin E levels were in the normal range ( ( 13.0±2.88 mg//L vs. 14.79±3.12 mg//L ; NS ) ) . On the contrary , basal MDA levels were higher than those observed in the control group ( ( 1.87±0.36 vs. 1.13±0.18 mmol//mL ; p < 0.01 ) ) and a significant decrease of MDA levels was found after 1 month of Excebrane ® treatment ( ( 1.39±0.25 nmol//mL ; p < 0.02 ) ) . In conclusion , the role of the “ oxidative hemolysis ” in the pathogenesis of anemia in CHD patients is still not clearly defined , but it could be of minor clinical relevance . Although the effectiveness of vitamin E‐‐coated membranes as a scavenger of ROS allows a better control of intradialytic oxidative stress , it does n't seem to contribute to clinical management of anemia in these patients Background : End-stage renal disease is a state of enhanced oxidative stress ( OS ) and hemodialysis ( HD ) and renal anemia further augment this disbalance . Anemia correction with erythropoietin ( EPO ) may improve oxidative status . However , there is no evidence of time dependent effects of EPO therapy on redox status of HD patients . Objective : The aim of this study was to evaluate whether the duration of EPO treatment may affect OS parameters in uremic patients . Patients and methods : 104 HD patients and 29 healthy volunteers were included . Patients were divided into 3 groups according to the duration of EPO treatment . Forth group consisted of HD patients without EPO treatment . Plasma and erythrocyte malondialdehyde ( MDA , MDArbc ) , reactive carbonyl groups ( RCG ) , plasma sulfhydryl ( -SH ) groups and total antioxidative capacity ( TAC ) levels were evaluated . Results : HD patients both with and without EPO treatment , showed a significant increase in all oxidative parameters without significance between EPO treated and -untreated group . The decrease in MDA and MDArbc levels coincided with the duration of EPO treatment . A negative correlation was observed between the duration of EPO treatment and serum MDA ( r=˗0.309 , p=0.003 ) . Increasing periods of EPO treatment were associated with decrease in RCG , without significance between EPO groups . Increase in TAC accompanied increasing duration s of EPO treatment , with EPO treatment for more than 24 months causing the most striking changes ( p<0.05 ) . There were no significant differences in ˗SH levels between EPO subgroups . Conclusion : Our results suggest that long term administration of EPO attenuated the lipid peroxidation process and restored the levels of antioxidants 1 Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase‐1 ( PON1 ) activity and an increased degree of oxidative stress compared with normal subjects . The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin ( EPO ) β and iron on levels of antibodies against oxidized low‐density lipoproteins ( ox‐LDL ) , as well as on serum PON1 activity and concentration , in predialysis patients with chronic renal disease . 2 Forty‐nine patients with chronic renal failure and haemoglobin ( Hb ) < 11 g/dL were treated over a period of 6 months with EPOβ ( 80–120 U/kg per week , s.c . ) and variable doses of iron . Selected biochemical variables were determined before and after treatment . 3 Treatment with EPOβ and iron was associated with a significant increase in mean ( ±SD ) blood Hb concentration compared with pretreatment values ( 12.8 ± 1.5 vs 9.9 ± 0.6 g/dL , respectively ; P < 0.001 ) . The average dose of EPOβ was 6160 ± 3000 U/week . After 6 months of treatment , compared with pretreatment values , the median levels ( 95 % confidence intervals ) of antibodies against ox‐LDL were decreased ( 17.5 ( 10.6–24.4 ) vs 24.8 ( 11.5–38.1 ) U/mL , respectively ; P < 0.001 ) , serum PON1 activity was slightly but significantly increased ( 123.6 ( 76.1–343.6 ) vs 101.0 ( 50.0–332.5 ) U/L , respectively ; P = 0.016 ) and the concentration of PON1 was significantly decreased ( 37.3 ( 11.8–76.2 ) vs 46.7 ( 24.6–98.0 ) mg/L , respectively ; P < 0.001 ) . There were no significant changes in total cholesterol , triglycerides or cholesterol fraction concentrations before and after treatment . 4 We suggest that EPOβ and iron treatment of anaemia promotes significant changes in serum PON1 activity and concentration and has a beneficial effect on oxidative stress in predialysis patients with chronic renal disease Background / Aim : Oxidative stress is known to be enhanced in hemodialysis patients , and one of its useful markers is plasma copper/zinc superoxide dismutase ( Cu/Zn-SOD ) . The increase in plasma Cu/Zn-SOD can be inhibited by orally administered lipid-soluble vitamin E. We examined the antioxidative effects of water-soluble vitamin C administered orally on Cu/Zn-SOD levels in hemodialysis patients . Methods : Vitamin C was orally administered to 16 maintenance hemodialysis patients before each dialysis session . Doses were increased from 200 to 1,000 mg over 3 months . The levels of plasma vitamin C and Cu/Zn-SOD and its mRNA expression in leukocytes were determined 1 , 2 , and 3 months after the start of vitamin C administration . Furthermore , the levels of oxidized and reduced forms of plasma vitamin C were determined before the start of vitamin C administration and before and after dialysis at 1,000-mg vitamin C doses . Results : Following oral administration , the plasma levels of vitamin C and its oxidized form were increased . However , significant changes in plasma Cu/Zn-SOD or its mRNA expression in leukocytes were not observed . Conclusion : In maintenance hemodialysis patients , vitamin C administration result ed in a significant increase in the postdialysis level of the oxidized form of vitamin C , which suggested an increase in antioxidant effect . However , water-soluble vitamin C did not significantly suppress Cu/Zn-SOD expression enhancement OBJECTIVE To evaluate the intake and status of antioxidants in chronic kidney disease ( CKD ) patients . DESIGN R and omized control trial . SETTING Hospital outpatient department . SUBJECTS One hundred eighty-five subjects ( 145 predialysis CKD patients and 40 apparently healthy controls ) were enrolled for this study . The patients were divided into moderate and severe renal failure groups based on their creatinine and glomerular filtration rates . INTERVENTION All patients completed a food frequency question naire , 24-hour dietary recall form , and anthropometric measurements and underwent biochemical and antioxidant lab tests . MAIN OUTCOME MEASURES Dietary intake , anthropometry , biochemical measures of blood and antioxidant enzymes as well as oxidative stress . RESULTS Overall , the diet was significantly lower in antioxidant-rich food intake in all the CKD patients as compared with controls . The oxidative stress measured in blood was found to be in consonance with the intake from diet . CONCLUSION Micronutrients play a major role in the antioxidant status of the patients and must be monitored , as deficiency of these might elevate the oxidative stress of the body , especially in the chronic diseases BACKGROUND Patients with end-stage renal failure , whether on conservative or haemodialysis therapy , have a high incidence of DNA damage . It is not known if improved control of the uraemic state by daily haemodialysis ( DHD ) reduces DNA lesions . METHODS DNA damage in peripheral blood lymphocytes ( PBLs ) was evaluated in a cross-sectional study of 13 patients on DHD ( 2 - 3 h , 6 times/week ) , 12 patients on st and ard haemodialysis ( SHD ) therapy ( 4 - 5 h , 3 times/week ) and 12 healthy age-matched volunteer controls . The biomarker of DNA damage used was micronucleus frequency . The assessed plasma parameters of microinflammation and oxidative stress were C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , neopterin , advanced oxidation protein products ( AOPP ) , and homocysteine . We also measured plasma concentrations of the circulating advanced glycation end products ( AGEs ) MGI ( methylglyoxal-derived imidazolinone ) , CML ( carboxymethyllysine ) , imidazolone A ( 3-deoxyglucosone-derived imidazolinone ) and AGE-associated fluorescence . RESULTS Compared to SHD , DHD was associated with significantly lower DNA damage , approaching the normal range . Micronuclei ( MN ) frequency averaged 29.1 MN+/-5.9/1000 binucleated ( BN ) cells in the SHD group , which is significantly elevated ( P<0.01 ) , 14.8 MN+/-4.0/1000 BN cells in the DHD group , and 13.2 MN+/-3.04/1000 BN cells in the controls . CRP and AOPP were in the normal range ( and similar between the dialysis groups ) . In contrast , IL-6 and neopterin were significantly elevated , with lower values associated with DHD as compared with SHD . The increased levels of AGEs tended to be lower in the DHD group , reaching significance for CML and imidazolone A. CONCLUSIONS Overall , it was found that genomic damage in PBLs is lower in patients on DHD than in those on SHD . Lower plasma concentrations of uraemic toxins , including circulating AGEs , may account for the differences . To confirm these data , prospect i ve clinical trials need to be performed BACKGROUND Atherosclerosis , a major problem in patients on chronic hemodialysis , has been characterized as an inflammatory disease . C-reactive protein ( CRP ) , the prototypical acute phase protein in humans , is a predictor of cardiovascular mortality in the general population . We hypothesize that several of the classic , as well as nontraditional , cardiovascular risk factors may respond to acute phase reactions . An activated acute phase response may influence or predict cardiovascular risk . METHODS In 280 stable hemodialysis patients , serum lipids , apolipoproteins ( apo ) A-I and B , lipoprotein(a ) [ Lp(a ) ] , fibrinogen , and serum albumin ( Salb ) were determined in relation to CRP and serum amyloid A ( SAA ) , two sensitive markers of an acute phase response . Mortality was monitored prospect ively over a two year period . RESULTS Serum CRP and SAA were found to be elevated ( more than 8 and more than 10 mg/liter , respectively ) in 46 % and 47 % of the patients in the absence of clinical ly apparent infection . Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a ) , higher plasma fibrinogen , and lower serum levels of high-density lipoprotein cholesterol , apo A-I , and Salb than patients with normal CRP or SAA . The rise in Lp(a ) concentration was restricted to patients exhibiting high molecular weight apo(a ) isoforms . During follow-up , 72 patients ( 25.7 % ) had died , mostly due to cardiovascular events ( 58 % ) . Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP ( 31 % vs. 16 % , P < 0.0001 , and 23 % vs. 5 % , P < 0.0001 , respectively ) or SAA ( 29 % vs. 19 % , P = 0.004 , and 20 vs. 10 % , P = 0.008 , respectively ) and were also higher in patients with Salb of lower than 40 g/liter ( 44 % vs. 14 % , P < 0.0001 , and 34 % vs. 6 % , P < 0.0001 , respectively ) . Univariate Cox regression analysis demonstrated that age , diabetes , pre-existing cardiovascular disease , body mass index , CRP , SAA , Salb , fibrinogen , apo A-I , and Lp(a ) were significantly associated with the risk of all-cause and cardiovascular mortality . During multivariate regression analysis , SAA , fibrinogen , apo A-I , and Lp(a ) lost their predictive values , but age and CRP remained powerful independent predictors of both overall death and cardiovascular death . CONCLUSION These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response , which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death . The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified . A successful treatment of the inflammatory condition may improve long-term survival in these patients Patients studied here suffered from chronic colitis characterized by vague lower abdominal pain , bleeding per rectum with diarrhoea and palpable tender descending and sigmoid colon . The inflammatory process in colitis is associated with increased formation of leukotrienes causing chemotaxis , chemokinesis , synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes . The key enzyme for leukotriene bio synthesis is 5-lipoxygenase . Boswellic acids were found to be non-redox , non-competitive specific inhibitors of the enzyme 5-lipoxygenase . We studied the gum resin of Boswellia serrata for the treatment of this disease . Thirty patients , 17 males and 13 females in the age range of 18 to 48 years with chronic colitis were included in this study . Twenty patients were given a preparation of the gum resin of Boswellia serrata ( 900 mg daily divided in three doses for 6 weeks ) and ten patients were given sulfasalazine ( 3 gm daily divided in three doses for 6 weeks ) and served as controls . Out of 20 patients treated with Boswellia gum resin 18 patients showed an improvement in one or more of the parameters : including stool properties , histopathology as well as scanning electron microscopy , besides haemoglobin , serum iron , calcium , phosphorus , proteins , total leukocytes and eosinophils . In the control group 6 out of 10 patients showed similar results with the same parameters . Out of 20 patients treated with Boswellia gum resin 14 went into remission while in case of sulfasalazine remission rate was 4 out of 10 . In conclusion , this study shows that a gum resin preparation from Boswellia serrata could be effective in the treatment of chronic colitis with minimal side effects End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentrations of certain essential and non-essential trace metals and high oxidative stress . We evaluated the effects of zinc ( Zn ) supplementation on plasma aluminum ( Al ) and selenium ( Se ) concentrations and oxidative stress in chronic dialysis patients . Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentrations ( HA group , Al > 50 μg/L ; and MA group , Al > 30 to ≤ 50 μg/L ) . All patients received daily oral Zn supplements for two months . Age- and gender-matched healthy individuals did not receive Zn supplement . Clinical variables were assessed before , at one month , and after the supplementation period . Compared with healthy subjects , patients had significantly lower baseline plasma Se concentrations and higher oxidative stress status . After two-month Zn treatment , these patients had higher plasma Zn and Se concentrations , reduced plasma Al concentrations and oxidative stress . Furthermore , increased plasma Zn concentrations were related to the concentrations of Al , Se , oxidative product malondialdehyde ( MDA ) , and antioxidant enzyme superoxide dismutase activities . In conclusion , Zn supplementation ameliorates abnormally high plasma Al concentrations and oxidative stress and improves Se status in long-term dialysis patients BACKGROUND This study focused on the effect of vitamin C on the 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) level of cellular DNA , as well as 8-oxoguanine-DNA glycosylase 1 ( hOGG1 ) and human MutT homologue ( hMTH1 ) gene expression in peripheral blood lymphocytes of chronic hemodialysis patients . METHODS Sixty chronic hemodialysis patients ( 35 men and 25 women ) were recruited to participate in a r and omized , placebo-controlled study . Treatment order is block-r and omized with intravenous sodium ascorbate ( vitamin C , 300 mg ) or placebo ( 0.9 % saline ) , administered postdialysis three times a week . We evaluated 8-OHdG level , intracellular reactive oxygen species ( ROS ) production , and gene expression of hOGG1 and hMTH1 in peripheral blood lymphocytes by using high-performance liquid chromatography ( HPLC ) electrochemical detection method , flow cytometric analysis , and reverse transcription-polymerase chain reaction ( RT-PCR ) , respectively . RESULTS A total of 51 patients completed the study ( 26 in placebo group and 25 in vitamin C group ) . Mean 8-OHdG levels significantly decreased in total subjects following 8 weeks of vitamin C supplementation ( 22.9 vs. 18.8/10(6 ) dG , P < 0.01 ) . The decrease in 8-OHdG levels after vitamin C supplementation was also noted in the patients with ferritin < 500 or > or = 500 microg/L and transferrin saturation ( TSAT ) < 50 or > or = 50 % ( P < 0.05 ) . But 8-OHdG levels had no significant changes in total patients or in the four subgroups of patients treated with placebo as compared to their baselines . Intracellular ROS production by lymphocytes from the four subgroups of patients , either spontaneous ( P < 0.05 ) or phorbol-12-myristate-13-acetate (PMA)-stimulated ( P < 0.001 ) , was significantly reduced after 8 weeks vitamin C supplementation . Steady-state hOGG1 mRNA levels were significantly up-regulated at 24 hours after vitamin C administration ( P < 0.05 ) , but hMTH1 mRNA levels were not . The changes in the spontaneous and PMA-stimulated ROS production , and an up-regulation of hOGG1 mRNA expression were not observed in patients treated with placebo as compared to their baselines . CONCLUSION Vitamin C supplementation in chronic hemodialysis patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS production , as well as up-regulate hOGG1 gene expression for repair . There is no compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte DNA base oxidation , even in the status of increased iron stores This clinical trial aim ed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation , and oxidative stress among type II diabetic patients . Forty patients with type II diabetes mellitus aged 35–68 years were assigned to two groups in this r and omized , double-blind , controlled clinical trial . Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7 , while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks . Fasting blood sample s , anthropometric measurements , and 24-h dietary recalls were collected at the baseline and at the end of the study , respectively . Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region ( P < 0.01 and P < 0.0001 , respectively ) compared with the baseline values , while plasma concentration of 8-hydroxy-2′-deoxyguanosine ( 8-OHdG ) decreased significantly compared with soy milk ( P < 0.05 ) . In addition , a significant increase in superoxide dismutase ( SOD ) activity was observed in probiotic soy milk group compared with baseline value ( P < 0.01 ) . There were no significant changes from baseline in the promoter methylation of MSH2 within either group ( P > 0.05 ) . The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients , indicating that probiotic soy milk is a promising agent for diabetes management BACKGROUND Patients with end-stage renal failure undergoing haemodialysis ( HD ) are exposed to oxidative stress . Increased levels of malondialdehyde ( MDA ) were demonstrated in plasma of uraemic patients , indicating accelerated lipid peroxidation ( LPO ) as a consequence of multiple pathogenetic factors . The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients . METHODS MDA and 4-hydroxynonenal ( HNE ) were measured in three groups of patients undergoing HD : group I comprised eight patients with a blood haemoglobin ( Hb ) < 10 g/dl ( mean Hb = 8.1+/-1.3 g/dl ) , and group II were eight patients with a Hb > 10 g/dl ( mean Hb=12.4+/-1.9g/dl ) ; none of these 16 patients had been treated with human recombinant erythropoietin ( rHuEpo ) . Group III comprised 27 patients with a mean Hb of 10.5+/-1.6 g/dl after long-term rHuEpo treatment . RESULTS Mean plasma concentrations of both MDA and HNE were significantly higher ( P<0.0001 ) in all 43 HD patients than in 20 healthy controls ( MDA 2.85+/-0.25 vs 0.37+/-0.03 microM , HNE 0.32+/-0.03 vs 0.10+/-0.01 microM ) . Comparing the three groups , it was shown that HD patients with a Hb < 10 g/dl had significantly higher plasma levels of LPO products ( MDA 3.81+/-0.86 microM , HNE 0.45+/-0.07 microM ) than HD patients with a Hb > 10g/dl ( MDA 2.77+/-0.58 UM , HNE 0.25+/-0.05 microM ) , and than HD patients treated with rHuEpo ( MDA 2.50+/-0.12 microM , HNE 0.29+/-0.03 microM ) . Furthermore , an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen ( r=0.62 , P<0.0001 ) . CONCLUSION Radical generation in HD patients might be caused in part by renal anemia itself . Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration BACKGROUND There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients . Limited data , however , are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients . METHODS We ran a prospect i ve , r and omized , open-label trial to assess the effects of oral vitamin C supplementation ( 250 mg three times per week ) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis ( HD ) patients . RESULTS Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls , C-reactive protein and albumin , or erythrocyte concentrations of reduced and oxidized glutathione . CONCLUSION Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients . Whether a higher oral dose or the intravenous route can modify these markers remains to be determined Increased peroxidation of lipids in red blood cells ( RBC ) in patients with advanced chronic renal failure ( CRF ) reflects increased generation of reactive oxygen species ( ROS ) , which may contribute to the metabolic damage induced by CRF and to its progression . We have evaluated parameters indicative of lipoperoxidation ( LPO ) of RBC at baseline in patients with CRF compared to controls , and the effects of a very low protein diet supplemented with amino and keto acids and vitamins A , C , E ( VLPD ) over a 6-month period . The presence of peroxidation damage in CRF patients before the administration VLPD was demonstrated by elevated levels of free malondialdehyde ( MDA ) ( p < .0003 ) and decreased levels of polyunsaturated fatty acids ( PUFA ) , particularly C20:4 ( p < .001 ) , C22:4 ( p < .0001 ) and C22:5 ( p < .0001 ) when compared to controls . Similarly , RBC vitamin E content was significantly decreased ( p < .0001 ) while enzymatic activities were unalterated . VLPD reduced erythrocyte LPO as suggested by ( a ) decreased levels of free and total RBC MDA ( p < .003 and p < .03 , respectively ) , ( b ) increased levels of PUFA , particularly C22:4 and C22:5 ( p < .003 and p < .03 , respectively ) , and ( c ) increased levels of vitamins A and E ( p < .001 and p < .04 , respectively ) as compared to prediet results . Antioxidant enzyme activities were not modified . These results suggest that VLPD has a protective role against LPO of erythrocytes in patients with CRF Chronic renal failure ( CRF ) is associated with oxidative stress , the precise mechanism of which is yet to be eluci date d. The present study was undertaken to investigate in renal insufficiency the expression of catalase and glutathione peroxidase , which play a critical role in antioxidant defense system by catalyzing detoxification of hydrogen peroxide ( H2O2 ) and organic hydroperoxides . Rats were r and omly assigned to the CRF ( 5/6 nephrectomized ) and sham-operated control groups and observed for 6 weeks . Renal and thoracic aortic catalase and glutathione peroxidase protein abundance was measured by Western blotting . The enzyme activities in the renal and aortic extracts , hepatic glutathione levels , blood pressure and urinary nitric oxide metabolites ( NO(x ) ) excretion were also measured . Blood pressure and urinary nitric oxide metabolite ( NO(x ) ) excretion were also measured . The CRF group showed a significant down-regulation of both immunodetectable catalase and glutathione peroxidase proteins in the remnant kidney . Catalase activity was also significantly decreased in the remnant kidney whereas glutathione peroxidase activity was not significantly affected . Furthermore , the protein abundance of catalase was unchanged whereas the enzyme activity was significantly decreased in the thoracic aorta of CRF animals compared to the sham-operated controls . By contrast , both the protein abundance and the enzyme activity of glutathione peroxidase were not significantly affected in the aorta of CRF animals compared to the sham-operated controls . This was coupled with marked arterial hypertension , significant reduction of hepatic glutathione levels and urinary NO(x ) excretion pointing to increased inactivation and sequestration of NO by superoxide . These events point to the role of impaired antioxidant defense system in the pathogenesis of oxidative stress in CRF BACKGROUND Intravenous iron administration ( IVIR ) is effective for correcting anemia in hemodialysis ( HD ) patients . However , it may also enhance the generation of hydroxyl radicals . Recently , plasma proteins have been demonstrated to be extremely susceptible to oxidative stress . Therefore , we investigated the effect of IVIR on the oxidative status of albumin , a major plasma protein , in HD patients . METHODS Eleven hemodialysis ( HD ) patients were treated with 40 mg of saccharated ferric oxide intravenously after every dialysis session for four weeks , and 11 age-/gender-matched HD patients were treated with vehicle . We performed high performance liquid chromatography ( HPLC ) analysis of serum albumin and determined the levels of reduced and oxidized albumin . Carbonyl formation of plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine antibody in patients with or without IVIR . RESULTS IVIR result ed in an increase in both disulfide form ( f(HNA-1 ) ) and oxidized form ( f(HNA-2 ) ) of albumin in HD patients ( 36.0 + /- 6.03 vs. 41.7 + /- 6.27 ; 5.46 + /- 1.50 vs. 8.7 + /- 2.22 , respectively , P < 0.05 ) . The findings here also show that IVIR substantially increased plasma protein carbonyl content by oxidizing albumin . In addition , we found a strong correlation between plasma carbonyl content and the levels of oxidized albumin ( f(HNA-1 ) and f(HNA-2 ) ) in HD patients ( R= 0.674 and R= 0.724 , respectively , P < 0.01 ) . CONCLUSION The results of this study indicate that the HPLC analysis of serum albumin represents a potentially useful method for the quantitative and qualitative evaluation of oxidative stress in HD patients , and strongly suggest the possibility that oxidative stress , generated by IVIR , enhances the oxidation of albumin in those patients Patients with chronic renal failure , particularly those undergoing regular dialysis treatment ( RDT ) are c and i date s for free radical damage . It is difficult to quantitate free radicals because of their short half-lives and reactive nature . Therefore , indirect methods measuring products of lipid peroxidation and protein oxidation are preferred . The present study displays a profile of lipid peroxidation and protein oxidation parameters , which are more sensitive and specific than the widely used method measuring thiobarbituric acid reactive substances ( TBARS ) , adapted to the plasma and erythrocyte sample s of RDT patients . We have observed increased levels of plasma and erythrocyte lipid peroxidation and also demonstrated increased protein oxidation in erythrocyte membranes of RDT patients The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades . However , r and omized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect . Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined . We defined the dose-dependent effects of vitamin E ( RRR-alpha-tocopherol ) to suppress plasma concentrations of F2-isoprostanes , a biomarker of free radical-mediated lipid peroxidation , in participants with polygenic hypercholesterolemia and enhanced oxidative stress , a population at risk for cardiovascular events . A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks . A dose-ranging study was then performed in participants supplemented with 0 , 100 , 200 , 400 , 800 , 1600 , or 3200 IU/day of vitamin E for 16 weeks . In the time-course study , maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation . In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU ( 35+/-2 % , p<0.035 ) and 3200 IU ( 49+/-10 % , p<0.005 ) . This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease BACKGROUND Patients suffering from chronic renal failure ( CRF ) are exposed to increased oxidative stress generated by uremic toxins , factors connected with hemodialysis , chronic inflammatory state , lack of vitamins A , E and selenium , advanced age , and parenteral iron administration . Their antioxidative system is inefficient . In erythrocytes , hexosemonophosphate ( HMP ) cycle does not assure an adequate amount of reductive equivalents ( NADPH ) necessary to restore reduced glutathione ( GSH ) , an important free radical scavenger . Hemodialysis treatment also causes a large loss of glucose , which is the basic substrate for that metabolic pathway . The object of the research was to establish the influence of glucose present in dialysate on antioxidant defense system in red blood cells . METHODS A group of 51 patients undergoing regular hemodialysis using glucose ( 26 subjects , GL+ HD ) or non-glucose fluid ( 25 subjects , GL- HD ) was studied . The GSH concentration , glucose-6-phosphate dehydrogenase ( G-6-P DH ) and glutathione reductase ( GSSG-R ) activities were determined . Glucose concentration before and after the hemodialysis session was also measured . RESULTS The activity of G-6-P DH was significantly higher in GL+ HD both before ( p = 0.000 ) and after ( p = 0.0002 ) the dialysis treatment compared to GL- HD , respectively , and to the healthy subjects ( p = 0.000 ) . The hemodialysis session caused a decrease in the activity of the enzyme in GL+ HD from 4.91 + /- 1.53 to 4.42 + /- 1.40 U/g Hb ( p = 0.004 ) as well as in GL- HD from 3.97 + /- 1.00 to 3.59 + /- 0.87 U/g Hb ( p = 0.007 ) . The GSSG-R showed an increase in activity in CRF patients before HD ( in GL+ HD to 2.57 + /- 0.76 and in GL- HD to 2.82 + /- 0.98 U/gHb ) . After dialysis , lower values were observed , particularly in GL+ HD ( 2.05 + /- 0.59 U/g Hb , p = 0.004 ) . GSH concentrations in the examined group were higher ( in GL+ HD 0.0205 + /- 0.008 and in GL- HD 0.0196 + /- 0.008 mmol/g Hb ) than in controlled subjects ( 0.0142 + /- 0.002 mmol/g Hb ) and decreased during dialysis treatment ( considerably only in GL- HD to 0.0183 + /- 0.007 mmol/g Hb , p = 0.056 ) . Glucose concentrations in GL+ HD were significantly higher compared to GL- HD ( p < 0.002 ) . CONCLUSIONS Glucose presence in dialyzing fluid improves the HMP cycle activity as well as glutathione system reactions and determines a better antioxidant status of erythrocytes . It limits hemolysis and improves the hematological parameters in CRF Abstract Chronic kidney disease ( CKD ) is characterized by a continuous reduction in kidney function , increased inflammation , and reduced antioxidant capacity . The objective of this study was to assess the effects of a herbal supplement on systemic inflammation and antioxidant status in non-dialysis CKD patients . Sixteen patients with CKD ( 56.0±16.0 yrs , 171.4±11.9 cm , 99.3±20.2 kg ) were r and omly chosen to receive a herbal supplement composed of Curcuma longa and Boswellia serrata , or placebo . Plasma levels of interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , glutathione peroxidase ( GPx ) , and serum C-reactive protein ( CRP ) were measured at baseline and 8 weeks . Baseline data demonstrated elevated inflammation and low antioxidant levels . A significant time effect ( p=0.03 ) and time x compliance interaction effect ( p=0.04 ) were observed for IL-6 . No significant differences were observed for any other variables . This study demonstrates that mild and moderate CKD is associated with chronic inflammation and low antioxidant activity . Systemic inflammation and impaired antioxidant status may be greater in CKD population s with multiple comorbidities . Curcumin and Boswellia serrata are safe and tolerable and helped to improve the levels of an inflammatory cytokine Renal failure is accompanied by oxidative stress , which is caused by enhanced production of reactive oxygen species ( ROS ) and an impaired antioxidant defense . We studied 73 hemodialysis ( HD ) patients ( 39 males and 34 females ) aged 24 - 75 years ; the patients were r and omized into two subgroups according to the type of hemodialysis membrane ( 35 patients were dialyzed on cellulose and 38 patients on polysulfone F7/F9 membrane dialyzers ) and we assessed their antioxidant and lipid peroxidation status levels . The total antioxidant status ( TAS ) levels including whole blood levels of malondialdehyde ( MDA ) and glutathione ( GSH ) ; glutathione peroxidase ( GSH-Px ) , superoxide dismutase ( SOD ) , and catalase ( CAT ) activities were measured , before and after hemodialysis . The MDA levels significantly increased 52.0 % and 16.9 % post dialysis among the cellulose and the polysulfone dialyzer users , respectively , ( P<0.05 ) . The TAS levels significantly decreased , 22.0 and 16.5 % in the cellulose and polysulfone dialyzer users , respectively , ( P<0.05 ) . The erythrocyte SOD activity decreased 25.1 and 19.1 % in the cellulose and the polysulfone dialyzer users , respectively , ( P<0.05 ) . The GSH concentrations , post dialysis , decreased 49.9 and 6.8 % in the cellulose and polysulfone dialyzer users , respectively , ( P<0.05 ) . In contrast , the erythrocyte activity of CAT , post dialysis , increased 15.0 and 37.3 % in the polysulfone and the cellulose dialyzer users , respectively , ( P<0.05 ) . We conclude that the type of the dialysis membrane affects the oxidative status after HD with possible consequences on patient morbidity and mortality Oxidative stress has been implicated in a range of disease states , including end-stage renal failure treated with hemodialysis . Hemodialysis with vitamin E-modified membranes reduces lipid peroxidation , but the effect on erythrocyte integrity has not been determined . This study compared antioxidant defense parameters and the resistance of erythrocytes to free radical-mediated hemolysis in patients dialysed with cellulose acetate membranes at baseline and with a vitamin E-modified membrane ( Excebrane Clirans ; Terumo Corporation ) for 13 wk . Resistance of erythrocytes to free radical attack was assessed in vitro using the peroxyl hemolysis test . The time to 50 % hemolysis ( T50 % ) increased significantly during the first 6 wk of Excebrane use ( p < 0.05 ) , but this parameter returned to baseline by 13 wk . Glutathione concentration and erythrocyte superoxide dismutase activity were unchanged during the study , but glutathione peroxidase activity increased from low levels at baseline and became significantly higher at 6 and 13 wk ( p < 0.001 ) . Total erythrocyte polyunsaturated fatty acid content and C18:2 level increased ( p < 0.001 ) and saturated fatty acids ( total , C16:0 , C18:0 , C22:0 and C24:0 ) decreased ( p < 0.03 ) . Total monounsaturated fatty acid content was unchanged . The increased resistance of erythrocytes to hemolysis , the increased glutathione peroxidase activity , and the increased degree of unsaturation of fatty acids in the erythrocyte membrane are compatible with a reduction of oxidative stress during hemodialysis with vitamin E-modified membranes Although the use of vitamin E supplements has been associated with a reduction in coronary events , assumed to be due to lowered lipid peroxidation , there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo . Here , we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes , a widely used marker of lipid peroxidation in vivo . As a study cohort , a subset of the “ Antioxidant Supplementation in Atherosclerosis Prevention ” ( ASAP ) study was used . ASAP is a double-masked placebo-controlled r and omized clinical trial to study the long-term effect of vitamin C ( 500 mg of slow release ascorbate daily ) , vitamin E ( 200 mg of d-α-tocopheryl acetate daily ) , both vitamins ( CellaVie ® ) , or placebo on lipid peroxidation , atherosclerotic progression , blood pressure and myocardial infa rct ion ( n = 520 at baseline ) . Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months . The plasma F2-isoprostane concentration was lowered by 17.3 % ( 95 % CI 3.9–30.8 % ) in the vitamin E group ( p = 0.006 for the change , as compared with the placebo group ) . On the contrary , vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group . There was also no interaction in the effect between these vitamins . In conclusion , long-term oral supplementation of clinical ly healthy , but hypercholesterolemic men , who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo , but a relatively high dose of vitamin C does not . This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis Background / Aims : Fast intravenous ( i.v . ) iron administration during hemodialysis ( HD ) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers , which are also induced by the hemodialysis procedure itself . The aim of this study was to investigate if slow i.v . iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session . Methods : Twenty dialysis patients 30–92 years of age that were iron replete and had values for hemoglobin , transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions . In the first session patients did not receive any iron treatment , whereas during the second and the third session patients received slow ( 60 min ) i.v . infusions of 100 mg of iron sucrose and 100 mg of iron dextran , respectively . Blood sample s were drawn before the hemodialysis session , 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions , for the measurement of markers of oxidant stress ( oxidized LDL and ischemia-modified albumin ) and inflammation ( high-sensitivity C-reactive protein , interleukin-6 and tumor necrosis factor-α ) . Results : Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied . In contrast , ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration . High-sensitivity CRP , IL-6 and TNF-α were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern . Conclusion : We did not find an increase in the markers of oxidation/inflammation studied , after slow i.v . iron administration during hemodialysis session Oxidized albumin is a reliable marker of oxidative stress in hemodialysis ( HD ) patients . However , oxidized albumin in vivo and its possible clinical significance has been rarely investigated . In the present study , the qualitative modification of albumin in HD patients ( n = 20 ) was examined and their results were compared with healthy age-matched controls ( n = 10 ) . The increase in plasma protein carbonyl levels in HD patients was largely due to an increase in oxidized albumin . Human serum albumin ( HSA ) of HD patients , HSA of HD patients ( HD-HSA ) and normal subjects ( Normal-HSA ) were purified on a blue Sepharose CL-6B column . Spectroscopic analysis confirmed that the HD-HSA sample s contained higher levels of carbonyls than Normal-HSA . An HPLC analysis also suggested that the state of the purified HSA used throughout the experiments accurately reflects the redox state of albumin in blood . HD-HSA was found to have a decreased the antioxidant activity , and was able to trigger the oxidative burst of human neutrophils , compared to Normal-HSA . HD-HSA was conformationally altered , with its hydrophobic regions more exposed and to have a negative charge . In binding experiments , HD-HSA showed impaired Site II-lig and binding capabilities . Collectively , the oxidation of plasma proteins , especially HSA , might enhance oxidative stress in HD patients BACKGROUND Oxidative stress has been implicated in the development of endothelial damage in hemodialysis ( HD ) . We have assessed the effects of N-acetylcysteine ( NAC ) , a compound with antioxidant effects , on malondialdehyde ( MDA ) , a marker of oxidative stress on lipid peroxidation . METHODS A clinical trial was conducted in which 24 chronic HD patients were divided into 2 groups according to gender , age , time on HD and cause of renal failure . The NAC group ( n = 12 ) received 600 mg of NAC twice a day for 30 days . The remaining patients constituted the control group ( n = 12 ) . MDA levels were measured pre- and post-dialysis at the beginning of the study ( baseline ) and on day 30 ( 30 days ) . RESULTS Baseline pre- and post-dialysis MDA levels were not different between both groups and were above normal values . A significant decrease was found in the NAC group when either pre- or post-dialysis MDA levels were compared to the corresponding control group levels on day 30 ( pre-dialysis NAC vs control group 3.01 + /- 0.6 vs 4.5 + /- 0.73 micromol/l , p < 0.0001 , post-dialysis NAC vs control group 2.76 + /- 0.5 vs 4.39 + /- 0.7 micromol/l , p < 0.0001 ) . Only in the NAC group were pre-dialysis MDA 30-day levels different from pre-dialysis baseline levels ( 3.01 + /- 0.6 vs 5.07 + /- 1.6 micromol/l , p < 0.002 ) . Post-dialysis MDA 30-day concentrations were significantly lower than post-dialysis MDA baseline levels ( 2.76 + /- 0.5 vs 4.32 + /- 0.7 micromol/l , p < 0.002 ) and pre-dialysis MDA 30-day measurements ( 2.76 + /- 0.5 vs 3.01 + /- 0.6 micromol/l , p < 0.011 ) . CONCLUSIONS MDA levels are elevated in chronic HD patients and are not significantly reduced by HD . NAC significantly reduces malondialdehyde levels in chronic HD patients Chronic hemodialysis ( HD ) patients increase erythrocyte susceptibility to hemolysis and impair cell survival . We explored whether electrolyte-reduced water ( ERW ) could palliate HD-evoked erythrocyte impairment and anemia . Forty-three patients undergoing chronic HD were enrolled and received ERW administration for 6 month . We evaluated oxidative stress in blood and plasma , erythrocyte methemoglobin (metHb)/ferricyanide reductase activity , plasma metHb , and proinflammatory cytokines in the chronic HD patients without treatment ( n=15 ) or with vitamin C (VC)- ( n=15 ) , vitamin E (VE)-coated dialyzer ( n=15 ) , or ERW treatment ( n=15 ) during an HD course . The patients showed marked increases ( 15-fold ) in blood reactive oxygen species , mostly H(2)O(2 ) , after HD without any treatment . HD result ed in decreased plasma VC , total antioxidant status , and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide ( PCOOH ) and plasma metHb . Antioxidants treatment significantly palliated single HD course-induced oxidative stress , plasma and RBC PCOOH , and plasma metHb levels , and preserved erythrocyte metHb /ferricyanide reductase activity in an order VC > ERW > VE-coated dialyzer . However , ERW had no side effects of oxalate accumulation easily induced by VC . Six-month ERW treatment increased hematocrit and attenuated proinflammatory cytokines profile in the HD patients . In conclusion , ERW treatment administration is effective in palliating HD-evoked oxidative stress , as indicated by lipid peroxidation , hemolysis , and overexpression of proinflammatory cytokines in HD patients BACKGROUND Cardiovascular disease is the principal cause of morbidity and mortality in haemodialysis patients . The classic risk factors do not account for all cases of elevated cardiovascular disease in this patient population and it is becoming increasingly clear that other cardiovascular risk factors are implicated . The objective of this study was to analyse whether or not C-reactive protein ( CRP ) and plasma copper oxidized anti-lipoprotein ( oxLDL ) antibody titre are risk factors for cardiovascular mortality during 4 years of follow-up . METHODS A prospect i ve follow-up study was carried out in 94 stable , chronic haemodialysis patients for 48 months ( July 1999-July 2003 ) ( gender : 50 males and 44 females ; mean age : 67+/-14 years ) . Eighty-four per cent of these patients were receiving intravenous erythropoietin and 63 % were receiving intravenous ferrotherapy ( iron gluconate ) . Basal markers of inflammation and oxidative stress were determined at the beginning of the study . CRP levels were determined by chemiluminescent enzyme-labelled immunometric assay . The oxLDL antibody titre was measured by enzyme-linked immunosorbent assay using native LDL and oxLDL as antigens . RESULTS Fifty deaths occurred during the study , 66 % ( n = 33 ) of which were due to cardiovascular disease . Patients presented with basal CRP and oxLDL levels indicative of chronic inflammation and elevated oxidative stress [ CRP median : 5.16 mg/l ( 25 - 75 % percentile : 0.35 - 88.7 mg/l ) ; oxLDL antibodies median : 153 ( optical density at 495 nm x 1000 ) ( 25 - 75 % percentile : 112 - 214 ) ] . A positive correlation was found between CRP and age ( r = 0.33 , P = 0.003 ) . Study of the risk factors demonstrated that age ( P = 0.007 ) , oxLDL antibody titre ( P = 0.04 ) and albumin ( P = 0.02 ) were the only predictors of cardiovascular mortality at 4 years of follow-up in this patient population . The Cox proportional hazards model for cardiovascular mortality showed that of the markers studied , oxLDL antibody titre was an independent risk factor for cardiovascular mortality . CONCLUSIONS Oxidative stress ( oxLDL antibody titre ) is one of the principal risk factors for cardiovascular mortality in this population of haemodialysis patients . Intravenous ferrotherapy , due to its pro-oxidant properties , probably favours oxidative stress . Serum concentration of CRP was not a good predictive factor of cardiovascular mortality during 4 years of follow-up , possibly because of the slight positive correlation that exists between CRP and age Background : Increased oxidative stress is associated with various complications in hemodialysis ( HD ) patients . Methods : We examined the effect of coenzyme Q10 ( CoQ10 ) administration on the plasma oxidative products and antioxidant capacity in 36 HD patients for 6 months . Results : The advanced oxidation protein products ( AOPP ) , malondialdehyde and the percentage of ubiquinone in total CoQ10 were significantly higher in HD patients than in healthy subjects before administration ( 0 month ) . Oxygen radical absorbing capacity ( ORAC ) and Trolox equivalent antioxidant capacity ( TEAC ) , indicators of total antioxidant capacity , were also paradoxically higher in the HD patients at 0 month . AOPP and the percentage of ubiquinone significantly decreased during CoQ10 administration , but increased again after the discontinuation . ORAC and TEAC were also decreased during CoQ10 administration . Conclusion : The CoQ10 administration was partially effective for suppressing the oxidative stress in HD patients . The unexpected decrease of ORAC and TEAC by CoQ10 seemed to be associated with a decreased oxidative stress OBJECTIVE We studied the effects of soy consumption on oxidative stress , blood homocysteine , coagulation factors , and phosphorus in peritoneal dialysis patients . DESIGN This was an unblinded , r and omized clinical trial . SETTING This study involved peritoneal dialysis centers in Tehran , Iran . PATIENTS We included 40 peritoneal dialysis patients ( 20 males and 20 females ) . INTERVENTION Peritoneal dialysis patients were r and omly assigned to either a soy or control group . Patients in the soy group received 28 g/day textured soy flour ( containing 14 g of soy protein ) for 8 weeks , whereas patients in the control group received their usual diet , without any soy . MAIN OUTCOME MEASURES Blood oxidized low-density lipoprotein ( ox-LDL ) , homocysteine , phosphorus , fibrinogen concentrations , and the activities of coagulation factors VII , IX , and X were measured at baseline and at the end of week 8 of the study . RESULTS The percentage of plasma coagulation factor IX activity decreased significantly by 17 % in the soy group at the end of week 8 compared with baseline ( P < .01 ) , and the reduction was significant compared with the control group ( P < .05 ) . There were no significant differences between the two groups in mean changes of blood ox-LDL , homocysteine , phosphorus , fibrinogen concentrations , and the activities of coagulation factors VII and X. CONCLUSION Soy consumption reduces plasma coagulation factor IX activity , which is a risk factor for thrombosis in peritoneal dialysis patients OBJECTIVE Although increased oxidative stress and inflammation are highly prevalent in chronic kidney disease ( CKD ) , few studies have investigated whether oral antioxidant therapy can alter markers of inflammation or oxidative stress in patients with CKD . The purpose of this study was to investigate whether a combination of mixed tocopherols and alpha lipoic acid ( ALA ) would alter biomarkers of oxidative stress and inflammation in subjects with stage 3 to 4 CKD . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled pilot trial . In all , 62 subjects were enrolled and were r and omly assigned to receive a combination of mixed tocopherols 666 IU/day , in addition to ALA 600 mg/day , or their matching placebos for a total of 8 weeks . Plasma F(2)-isoprostane and protein thiol concentration were measured as biomarkers of oxidative stress , and C-reactive protein and interleukin-6 concentration as biomarkers of systemic inflammation . RESULTS There were no significant differences in demographics , diabetic status , or estimated glomerular filtration rate between study treatment and placebo groups at baseline . Of the 62 r and omized subjects , 58 ( 93 % ) completed the study protocol . After 2 months of treatment , there were no significant changes in the concentrations of F(2)-isoprostanes , protein thiols , C-reactive protein , and interleukin-6 with respect to treatment with mixed tocopherols and ALA as compared with matching placebos , whether analyzed as intention to treat or as treated . Diabetic status and baseline body mass index did not influence the results . CONCLUSIONS Combination of oral mixed tocopherols and ALA treatment for 2 months does not influence biomarkers of oxidative stress and inflammation in patients with stage 3 to 4 CKD Background / Aims : The aim of this study was to assess the multifaceted influence of glucose present in dialyzing fluid on erythrocytes of patients with chronic renal failure ( CRF ) undergoing regular hemodialysis . Methods : A group of 44 subjects with CRF undergoing regular hemodialysis was studied . Two tests were used : osmotic fragility and resistance to the hemolytic agent saponin . The total content of isoprostane 8-iso-prostagl and in F2α type III ( 8-iPF2α-III ) in plasma and erythrocyte ’s membrane were determined by the ELISA method . Results : The presence of glucose in the dialysate is associated with lower intravascular hemolysis markers and high total 8-iPF2α-III concentrations in plasma . Conclusion : The presence of glucose in dialyzing fluid could protect erythrocytes . It limits hemolysis in patients with CRF , but , on the other h and , increases the oxidative processes . This kind of treatment along with other therapeutic intervention such as administration of antioxidants ( e.g. α-tocopherol , ascorbic acid , N-acetylcysteine ) could improve the condition of erythrocytes and outcome in CRF PURPOSE Hemodialyzed patients demonstrate elevated oxidative stress and reduced functional status . Exercise induces health benefits , but acute exertion up-regulates oxidative stress responses in patients undergoing hemodialysis . Therefore , the aim of the present study was to examine the effect of L-carnitine supplementation on i ) exercise performance and ii ) blood redox status both at rest and after exercise . METHODS Twelve hemodialysis patients received either L-carnitine ( 20 mg kg(-1 ) i.v . ) or placebo in a double-blind , placebo-controlled , counterbalanced , and crossover design for 8 wk . Participants performed an exercise test to exhaustion before and after supplementation . During the test , V˙O2 , respiratory quotient , heart rate , and time to exhaustion were monitored . Blood sample s , collected before and after exercise , were analyzed for lactate , malondialdehyde , protein carbonyls , reduced and oxidized glutathione , antioxidant capacity , catalase , and glutathione peroxidase activity . RESULTS Blood carnitine increased by L-carnitine supplementation proportionately at rest and after exercise . L-carnitine supplementation increased time to fatigue ( 22 % ) and decreased postexercise lactate ( 37 % ) , submaximal heart rate , and respiratory quotient but did not affect V˙O2peak . L-carnitine supplementation increased reduced/oxidized glutathione ( 2.7-fold at rest , 4-fold postexercise ) and glutathione peroxidase activity ( 4.5 % at rest , 10 % postexercise ) and decreased malondialdehyde ( 19 % at rest and postexercise ) and protein carbonyl ( 27 % at rest , 40 % postexercise ) concentration . CONCLUSIONS Data suggest that a 2-month L-carnitine supplementation may be effective in attenuating oxidative stress responses , enhancing antioxidant status , and improving performance of patients with end-stage renal disease Hemodialysis patients are prone to deficiency of vitamin C , which constitutes the most abundant nonenzymatic antioxidant in blood . Because antioxidants are involved in the pathogenesis of atherosclerosis , the authors examined the association of total vitamin C plasma level with cardiovascular outcomes in such patients . One hundred thirty-eight consecutive maintenance hemodialysis patients ( median age 61 yr , 90 males ) were enrolled in a single-center study . At baseline , routine laboratory parameters were recorded , and predialysis total vitamin C plasma levels were measured by high-pressure liquid chromatography . Patients were prospect ively followed-up for the occurrence of a primary composite endpoint consisting of fatal and nonfatal major adverse cardiovascular events ( MACE ) and for all-cause and cardiovascular mortality . MACE occurred in 35 patients ( 25 % ) over a period of median 30 mo , and 42 patients ( 30 % ) died [ 29 cardiovascular deaths ( 21 % of total ) ] . Using Cox proportional hazards modeling , adjusted hazard ratios for the occurrence of MACE were 3.90 ( 95 % confidence interval [ CI ] : 1.42 to 10.67 ; P = 0.008 ) and 3.03 ( 95 % CI : 1.03 to 8.92 ; P = 0.044 ) for patients in the lower ( < 32 micromol/L ) and middle ( 32 to 60 micromol/L ) tertile of total vitamin C levels , compared with patients in the upper tertile ( > 60 micromol/L ) . Hazard ratios for cardiovascular death were 3.79 ( 95 % CI : 1.23 to 11.66 ; P = 0.020 ) and 2.89 ( 95 % CI : 0.89 to 9.37 ; P = 0.076 ) . Total vitamin C levels were not independently associated with all-cause mortality . This study concludes that low total vitamin C plasma levels predict adverse cardiovascular outcomes among maintenance hemodialysis patients . Future studies should address the potential protective effect of an adequate vitamin C supplementation INTRODUCTION Accumulation of reactive oxygen species ( ROS ) takes place in patients with chronic renal failure ( CRF ) . Oxidative stress causes disorders in the activity of the sodium-proton exchanger ( NHE ) . Studies on NHE in CRF produced results that are discrepant and difficult to interpret . The aim of this study was to demonstrate that oxidative stress had an effect on the activity of NHE . METHODS We enrolled 87 subjects divided into 4 groups : patients with CRF treated conservatively ; patients with CRF hemodialyzed without glucose -- HD-g(- ) ; patients with CRF hemodialyzed with glucose -- HD-g(+ ) ; controls ( C ) . The activity of NHE , the rate of proton efflux V(max ) , Michaelis constant ( Km ) , and the concentration of thiobarbituric acid-reactive substances ( TBARS , an indicator of oxidative stress ) in plasma , as well as the concentration of reduced glutathione in blood were determined . RESULTS The concentration of TBARS was significantly higher in hemodialyzed patients before and after dialysis and in patients with CRF on conservative treatment in comparison with group C. TBARS in plasma correlated negatively with VpH(i)6.4 in group C and with V(max ) and VpH(i)6.4 after HD in group HD-g(- ) . We found that the concentration of creatinine correlated with TBARS ( p < 0.0001 ; r = + 0.51 ) in the conservatively treated group . CONCLUSION We observed a marked oxidative stress and decreased NHE activity when dialysis was done without glucose , whereas patients dialyzed with glucose demonstrated a relatively low intensity of oxidative stress Background and aims The objective of this study was to investigate the effect of Boswellia serrata extract ( BSE ) on symptoms , quality of life , and histology in patients with collagenous colitis . Material s and methods Patients with chronic diarrhea and histologically proven collagenous colitis were r and omized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo . Complete colonoscopy and histology were performed before and after treatment . Clinical symptoms and quality of life were assessed by st and ardized question naires and SF-36 . The primary endpoint was the percentage of patients with clinical remission after 6 weeks ( stool frequency ≤3 soft /solid stools per day on average during the last week ) . Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks . Results Thirty-one patients were r and omized ; 26 patients were available for per- protocol - analysis . After 6 weeks , the proportion of patients in clinical remission was higher in the BSE group than in the placebo group ( per protocol 63.6 % ; 95%CI , 30.8–89.1 vs 26.7 % , 95%CI , 7.7–55.1 ; p = 0.04 ; intention-to-treat 43.8 % vs 26.7 % , p = 0.25 ) . Compared to placebo , BSE treatment had no effect on histology and quality of life . Five patients discontinued BSE treatment prematurely . Discontinuation was due to adverse events ( n = 1 ) , unwillingness to continue ( n = 3 ) , or loss to follow-up for unknown reasons ( n = 1 ) . Seven patients received open-label BSE therapy , five of whom achieved complete remission . Conclusions Our study suggests that BSE might be clinical ly effective in patients with collagenous colitis . Larger trials are clearly necessary to establish the clinical efficacy of BSE |
11,116 | 17,022,907 | No effects were shown in preventing Down syndrome , pyloric stenosis , undescended testis , or hypospadias .
CONCLUSION Maternal consumption of folic acid-containing prenatal multivitamins is associated with decreased risk for several congenital anomalies , not only neural tube defects . | BACKGROUND The use of folic acid-fortified multivitamin supplements has long been associated with decreasing the risk of neural tube defects .
Several studies have also proposed the effectiveness of these supplements in preventing other birth defects ; however , such effects have never been systematic ally examined .
OBJECTIVE We conducted a systematic review and meta- analysis to evaluate the protective effect of folic acid-fortified multivitamin supplements on other congenital anomalies . | OBJECTIVE We evaluated the association between mothers ' use of multivitamin supplements and their infants ' risk for omphalocele , a congenital anomaly of the abdominal wall . Omphalocele can occur in certain multiple congenital anomaly patterns with neural tube defects , for which a protective effect of multivitamins with folic acid has been demonstrated . METHODS We used data from a population -based case-control study of infants born from 1968 - 1980 to mothers residing in metropolitan Atlanta . Case-infants with nonsyndromic omphalocele ( n = 72 ) were actively ascertained from multiple sources . Control-infants ( n = 3029 ) , without birth defects , were selected from birth certificates by stratified r and om sampling . RESULTS Compared with no use in the periconceptional period , periconceptional use of multivitamin supplements ( regular use from 3 months before pregnancy through the first trimester of pregnancy ) was associated with an odds ratio for nonsyndromic omphalocele of 0.4 ( 95 % confidence interval [ CI ] : 0.2 - 1.0 ) . For the subset comprising omphalocele alone or with selected midline defects ( neural tube defects , hypospadias , and bladder/cloacal exstrophy ) , the odds ratio was 0.3 ( 95 % CI : 0.1 - 0.9 ) . These estimates were similar when the reference group also included women who began using multivitamins late in pregnancy ( during the second or third month of pregnancy ) . The small number of participants limited the precision of subgroup analyses and translated into wide confidence intervals that included unity . CONCLUSIONS Periconceptional multivitamin use was associated with a 60 % reduction in the risk for nonsyndromic omphalocele . These findings await replication from additional studies to confirm the findings , generate more precise estimates , and detail possible mechanisms of actions To study the relation of maternal periconceptional vitamin use to the risk of a congenital urinary tract anomaly ( CUTA ) , we conducted a case-control study using the Washington State Birth Defect Registry . We identified CUTA cases with no known chromosomal abnormality in seven counties in western Washington State occurring between January 1 , 1990 , and December 31 , 1991 . We r and omly selected a sample , as controls , of all infants delivered in five large hospitals in King County who did not have a birth defect and who were born in the same year as the cases . About 55 % of all infants in King County and a smaller proportion of infants in the other six counties are delivered in these five hospitals . We interviewed mothers of 118 cases and 369 controls to obtain information about their vitamin use during the pregnancy and during the year before the conception . After adjustment for maternal race , family income , county of maternal residence , and birth year , we found that women who used multivitamins during the first trimester had only 15 % the risk of bearing a child with a CUTA compared with women who did not take vitamins [ odds ratio ( OR ) = 0.15 ; 95 % confidence interval ( CI ) = 0.05–0.43 ] . The reduction was smaller for use restricted to the second or third trimesters ( OR = 0.31 ; 95 % CI = 0.09–1.02 ) . Among women who used vitamins during the first trimester , vitamin use before conception was not associated with any further reduction in the risk , nor did there appear to be an association with the amount or br and of vitamin used . Restricting the analysis to residents of King County did not change the results . Our results indicate that prenatal multivitamin use , particularly during the first trimester , may reduce the risk of a CUTA . Because all of the preparations taken by study participants contained many vitamins as well as folic acid , it was not possible to identify which one ( or several ) chemical(s ) may have been responsible for the reduced risk of a CUTA OBJECTIVE --To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities . DESIGN --R and omised controlled trial of supplementation with multivitamins and trace elements . SETTING --Hungarian family planning programme . SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life . INTERVENTIONS --A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception . MAIN OUTCOME MEASURES --Number of major and mild congenital abnormalities . RESULTS --The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference can not be explained totally by the significant reduction of neural tube defects . The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group ; relative risk 1.85 ( 95 % confidence interval 1.02 to 3.38 ) ; difference , 7.6/1000 . The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group ; relative risk 1.95 ( 1.23 to 3.09 ) ; difference , 13.6/1000 . The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant . CONCLUSIONS --Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities . Further studies are needed to differentiate the chance effect and vitamin dependent effect A r and omised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid ( one of the vitamins in the B group ) or a mixture of seven other vitamins ( A , D , B1,B2,B6,C and nicotinamide ) around the time of conception can prevent neural tube defects ( anencephaly , spina bifida , encephalocele ) . A total of 1817 women at high risk of having a pregnancy with a neural tube defect , because of a previous affected pregnancy , were allocated at r and om to one of four groups -- namely , folic acid , other vitamins , both , or neither . 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect ; 27 of these had a known neural tube defect , 6 in the folic acid groups and 21 in the two other groups , a 72 % protective effect ( relative risk 0.28 , 95 % confidence interval 0.12 - 0.71 ) . The other vitamins showed no significant protective effect ( relative risk 0.80 , 95 % Cl 0.32 - 1.72 ) . There was no demonstrable harm from the folic acid supplementation , though the ability of the study to detect rare or slight adverse effects was limited . Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy , and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect . Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects , area of residence , immediately prior miscarriage , and interpregnancy interval . None of these factors , however , contributed any significant differential risk between supplemented and unsupplemented mothers . Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation OBJECTIVE In 1982 , Tolarova(4 ) found a reduction in the recurrence rate of isolated cleft lip ( CL ) with or without cleft palate ( CP ; CL + /- CP ) after periconceptional supplementation with a multivitamin including a very high dose ( 10 mg ) of folic acid . The Hungarian r and omized , double-blind , controlled trial of periconceptional supplementation with a multivitamin including a physiologic dose ( .8 mg ) of folic acid did not show any preventive effect on the first occurrence of isolated CL + /- CP and CP . However , the general evaluation of congenital abnormalities in the Hungarian Case-Control Surveillance of Congenital Abnormalities indicated , among others , a reduction of isolated CL + /- CP and CP after the use of high doses of folic acid in the critical period for the development of these congenital abnormalities in the 12-year data set between 1980 and 1991 . We hypothesized that the prevention of orofacial clefts by folic acid has a dose-dependent effect , and this hypothesis was tested in 2 recent Hungarian data sets . DESIGN In a prospect i ve cohort study , the occurrence of isolated CL + /- CP and CP was studied in the newborn infants born to mothers with or without periconceptional folic acid-containing ( .8 mg ) multivitamin supplementation . Supplemented women with confirmed pregnancy were recruited from the participants of the periconceptional service . Unsupplemented women were invited to take part in the study after the first visit between the 8th and 12th week of gestation in the antenatal care . Supplemented and unsupplemented women were matched based on age , socioeconomic status , and residence . In contrast , the occurrence of high-dose ( in general daily 6 mg ) folic acid supplementation was evaluated in the case-control pairs of CL + /- CP and CP , particularly during the critical period of these 2 types of orofacial clefts in the 17 years data set of the Case-Control Surveillance of Congenital Abnormalities , between 1980 and 1996 . Cases were selected from the population -based Hungarian Congenital Abnormality Registry , whereas population controls without congenital abnormality were ascertained from the national birth registry . Two population controls were matched to every case according to sex , week of birth , and district of parental residence . The drug uses , including pregnancy supplements as folic acid , were evaluated based on retrospective self-reported maternal question naire and prospect i ve medically documented data of antenatal care logbook . RESULTS In the prospect i ve cohort study , of 3019 informative offspring ( termination of pregnancies in the second and third trimesters because of fetal defect , stillborn fetuses , and liveborn infants ) in the supplemented group , 3 had CL + /- CP and 1 was affected with CP , whereas of 3432 informative offspring in the unsupplemented group , 2 had CL + /- CP and 1 had CP . The lack of preventive effect was in agreement with the result of the previous Hungarian r and omized double-blind controlled trial ; thus , these 2 data sets were combined . The preventive effect of a folic acid containing multivitamin used in the periconceptional period for the first occurrence of isolated CL + /- CP and CP was estimated by the Mantel-Haenszel test . Of 5488 supplemented women , 6 had CL + /- CP , and of 5821 unsupplemented women , 4 had CL + /- CP . Of 5489 supplemented women , 1 had CP , and of 5823 unsupplemented pregnant women , 3 had CP . The Hungarian Case-Control Surveillance of Congenital Abnormalities , 1980 - 1996 , included 38 151 population controls ( 1.8 % of the Hungarian births ) and 22 865 cases with congenital abnormalities . Within the latter group , 1368 had isolated CL + /- CP , and 596 had CP . A significantly more frequent use of high-dose folic acid ( in general daily 6 mg ) supplementation was found in controls than in cases of 1246 case-control pairs of CL + /- CP group and of 537 case-control pairs of CP group , respectively . ( ABSTRACT TRUNCATED A r and omised trial was initiated in Irel and in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects ( NTDs ) in women with a previously affected pregnancy from 5.0 % to 1.0 % or less . The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed . A total of 354 women were r and omised to receive one of three treatments : folic acid , multivitamins without folic acid , and folic acid plus multivitamins . At the end of the trial 257 women had had a first trial pregnancy outcome ( 261 infants/fetuses ) where the presence or absence of NTDs was ascertainable . There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups , a non-significant difference . Otherwise eligible women who were pregnant when first contacted constituted a non-r and omised control group ; there were three recurrences among the 103 infants in this group . The difference in the recurrence rate between the folic acid groups and the non-r and omised controls was statistically significant but we have reservations about the validity of this comparison . Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council ( MRC ) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial PURPOSE To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies . METHODS This population -based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 r and omly selected controls . Women completed a food frequency question naire and were interviewed about lifestyle behaviors , pregnancy histories and use of multivitamins . RESULTS Use of 0.4 mg or more of multivitamin folic acid at least 3 times per week during the periconceptional period showed no statistically significant reduction in NTD risk [ adjusted odds ratio ( AOR ) = 0.55 , 95 % confidence interval ( CI ) = 025 , 1.22 ] . After adjusting for covariates , protective effects for NTDs were observed at the highest quartiles of dietary folate and total folate ( daily dietary folate plus daily multivitamin folic acid ) ; the respective odds ratios were 0.40 ( 95 % CI = 0.19 , 0.84 ) and 0.35 ( 95 % CI = 0.17 , 0.72 ) . CONCLUSIONS This study illustrates some of the difficulties in determining effects of folic acid and dietary folate in a population where the consumption of foods rich in folate and the use of multivitamins are increasing and the rate of NTDs is declining . Studies are needed to monitor future changes in folate levels and their effect on health The purpose of this study was to assess the relation between maternal multivitamin use and risk for cardiac defects in the offspring , using a population -based approach . The Atlanta Birth Defects Case-Control study is a population -based case-control study of infants born between 1968 and 1980 to mothers residing in metropolitan Atlanta , Georgia . The 958 case infants with nonsyndromic cardiac defects were actively ascertained from multiple sources . The 3,029 infants without birth defects ( control infants ) were selected from birth certificates by stratified r and om sampling . Periconceptional multivitamin use , defined as reported regular use of multivitamins from 3 months before pregnancy through the first 3 months of pregnancy , was contrasted with no use during the same time period . Periconceptional multivitamin use was associated with a reduced risk for nonsyndromic cardiac defects in the offspring ( odds ratio ( OR ) = 0.76 ; 95 % confidence interval ( Cl ) : 0.60 , 0.97 ) . The risk reduction was strongest for outflow tract defects ( OR = 0.46 ; 95 % Cl 0.24 , 0.86 ) and ventricular septal defects ( OR = 0.61 ; 95 % Cl : 0.38 , 0.99 ) . No risk reduction was evident when multivitamin use was begun after the first month of pregnancy . If these associations are causal , the results suggest that approximately one in four major cardiac defects could be prevented by periconceptional multivitamin use BACKGROUND The 1984 - 1991 Hungarian r and omized controlled trial ( RCT ) of periconceptional multivitamin supplementation containing folic acid ( 0.8 mg ) showed a significant reduction in the first occurrence of neural tube defects ( NTDs ) , and of urinary tract and cardiovascular abnormalities , but no reduction in orofacial clefts . A controlled cohort trial was design ed to confirm or deny these results . METHODS Supplemented women were recruited from the Hungarian Periconceptional Service using the same multivitamin as the Hungarian RCT . Unsupplemented pregnant women were recruited in the st and ard regional antenatal care clinics and were matched to each supplemented pregnant woman on the basis of age , socioeconomic status , place of residence , and year of pregnancy . RESULTS A total of 3056 informative offspring were evaluated in each cohort . The occurrence of congenital cardiovascular malformations ( 31 vs. 50 ) was reduced ( odds ratio [ OR ] , 0.60 ; 95 % confidence interval [ CI ] , 0.38 - 0.96 ) in the supplemented cohort , accounted for mainly by ventricular septal defects ( 5 vs. 19 ; OR , 0.26 ; 95 % CI , 0.09 - 0.72 ) . There was no significant difference ( 14 vs. 19 ) in the occurrence of urinary tract defects between the two cohorts , but stenosis/atresia of pelvic-ureteric junction ( 2 vs. 13 ) showed a significant reduction ( OR , 0.19 ; 95 % CI , 0.04 - 0.86 ) . The protective effect of the folic acid-containing multivitamin for NTDs ( one offspring in the supplemented vs. nine in the unsupplemented cohort ) was confirmed ( OR , 0.11 ; 95 % CI , 0.01 - 0.91 ) . There was , however , no protective effect on orofacial clefts or on multiple congenital abnormalities . CONCLUSIONS The results of this cohort-controlled trial support the findings of the previous Hungarian RCT . The primary prevention of some major structural birth defects by multivitamins containing folic acid or by folic acid has great public health importance BACKGROUND & OBJECTIVES A folic acid containing multivitamin preparation was evaluated for its efficacy in preventing recurrence of open neural tube defect ( NTD ) in a blind , placebo-controlled r and omized trial . The trial was carried out at the five centres in India , viz . , Bangalore , Mumbai , Lucknow , New Delhi and Pune . METHODS The preparation contained 4 mg of folic acid besides calcium , iron , zinc and vitamins A , B1 , B2 , B6 , C , D and nicotinamide . The placebo contained calcium and iron only . A total of 466 women with previous history of giving birth to a child with open NTD were included in the trial ( 231 in the vitamin group and 235 in the placebo group ) . The supplementation was given for at least one month prior to conception and up to three months after conception . All women were offered antenatal diagnosis with screening of maternal serum alpha foetoprotein ( AFP ) and ultrasound . RESULTS Pregnancy outcome with reference to recurrence of NTD was unknown in 137 women in the vitamin group and 142 in the placebo group . The recurrence of open NTD in the vitamin group was 2.92 per cent compared to 7.04 per cent in the placebo group , a reduction by about 60 per cent . The difference , however , was not statistically significant ( P = 0.06 ) . INTERPRETATION & CONCLUSIONS The study seems to support the role of periconceptional folic acid supplementation in prevention of recurrence of NTDs in the Indian population . The reason for high recurrence rate observed in the placebo group requires further investigation Women who had previously given birth to one or more infants with a neural-tube defect ( NTD ) were recruited into a trial of periconceptional multivitamin supplementation . 1 of 178 infants/fetuses of fully supplemented mothers ( 0.6 % ) had an NTD , compared with 13 of 260 infants/fetuses of unsupplemented mothers ( 5.0 % ) The effect of periconceptional multivitamin/trace element supplementation on pregnancy outcomes was evaluated in a r and omised controlled trial . The final data -base included 5,502 females with confirmed pregnancy . A multivitamin including 0.8 mg folic acid or a trace element were supplemented for at least 28 days before conception and continuing for at least until the second missed menstrual period . Number of pregnancies , terminations of pregnancies , four types of fetal deaths , livebirths including low birth weight , preterm birth and sex ratio were analysed . Periconceptional multivitamin supplementation increased fertility ( higher rates of cumulative conceptions and multiple births ) , had no significant effect on the rate of different groups of fetal deaths , low birth weight and preterm birth in singletons . This primary preventive method can reduce the occurrence and recurrence of neural-tube defects and had no other significant effect on pregnancy outcomes except multiple births STUDY OBJECTIVE --The aim was to assess the association of neural tube defects with periconceptional vitamin supplementation . DESIGN --This was a matched , population based case-control study . SETTING --Western Australia , 1982 - 1984 . PARTICIPANTS --Mothers of 77 cases ( 93 % of those eligible ) with isolated neural tube defects , mothers of 77 matched control infants with defects other than neural tube defects ( control group I ) , and mothers of 154 liveborn , matched , control infants with no birth defects ( control group II ) participated in the study . MEASUREMENTS AND MAIN RESULTS --Information was collected by interview and self administered question naire . Crude and adjusted odds ratios ( and their 95 % confidence intervals ) showed a small but non-significant protective effect of folate supplementation in comparisons with both control groups . The adjusted ratios for the three months before pregnancy were 0.69 ( 0.06 , 8.53 ) with control group I , and 0.11 ( 0.01 , 1.33 ) with control group II . In the first six weeks of pregnancy , the adjusted odds ratios were 0.70 ( 0.32 , 1.52 ) with control group I and 0.74 ( 0.29 , 1.88 ) with control group II . The odds ratios for vitamin supplementation of any kind were all very close to or greater than one , and all confidence intervals embraced unity . CONCLUSIONS --These data do not provide evidence of an association between periconceptional vitamin supplementation and neural tube defects , although a protective effect of folate supplementation can not be excluded with confidence , due to the low power of the study . Of three other observational studies of vitamins and neural tube defects , two have shown an association . While further studies of this kind may be of value , evidence must now be sought from r and omised controlled trials The objective in the Hungarian r and omised double-blind controlled trial was to study the preventive effect of periconceptional multivitamin supplementation on neural tube-defects and other congenital abnormalities . There were 2,471 and 2,391 informative offspring ( prenatally diagnosed and terminated malformed fetuses , stillborn fetuses , and liveborn infants ) in the multivitamin and placebo-like trace element groups , respectively . A single tablet either of a multivitamin containing 0.8 mg of folic acid or trace element supplement was given daily for at least one month before conception and at least until the date of the second missed menstrual period . The total rate of major congenital abnormalities was 20.6/1,000 in the multivitamin and 40.6/1,000 in the trace element group . After the exclusion of six cases of neural-tube defects in the trace element group the difference was very highly significant [ P = 0.0003 ; relative risk of 0.54 ( 95 % CI 0.39 , 0.76 ) ] . Multivitamin supplementation appeared to result in a significant reduction in the rate of urinary tract abnormalities , mainly obstructive defects , and in the rate of sporadic cardiovascular malformations , mainly ventricular septal defects . This report is regarded as a hypothesis-generating study encouraging others to see if the result can be repeated OBJECTIVE The preventive efficacy of the periconceptional use of multivitamins is well established for neural tube defects , much less so for other birth defects . We conducted a population -based , case-control study to assess the effects of multivitamin use on the risk for conotruncal defects , a group of severe heart defects that includes transposition of the great arteries , tetralogy of Fallot , and truncus arteriosus . METHODS From the population -based Atlanta Birth Defects Case-Control Study , we identified 158 case infants with conotruncal defects and 3026 unaffected , r and omly chosen control infants , born from 1968 through 1980 to mothers residing in metropolitan Atlanta . Periconceptional multivitamin use was defined as reported regular use from 3 months before conception through the third month of pregnancy . We present the results of the crude analysis , because the multivariate model yielded essentially identical results . RESULTS Mothers who reported periconceptional multivitamin use had a 43 % lower risk of having infants with conotruncal defects ( odds ratio [ OR ] , 0.57 ; 95 % confidence interval [ CI ] , 0.33 to 1.00 ) than did mothers who reported no use . The estimated relative risk was lowest for isolated conotruncal defects ( OR , 0.41 ; 95 % CI , 0.20 to 0.84 ) compared with those associated with noncardiac defects ( OR , 0.91 ; 95 % CI , 0.33 to 2.52 ) or a recognized syndrome ( OR , 1.82 ; 95 % CI , 0.31 to 10.67 ) . Among anatomic subgroups of defects , transposition of the great arteries showed the greatest reduction in risk ( OR , 0.36 ; 95 % CI , 0.15 to 0.89 ) . CONCLUSIONS Periconceptional multivitamin use is associated with a reduced risk for conotruncal defects . These findings could have major implication s for the prevention of these birth defects We investigated whether a woman 's periconceptional use of a multivitamin containing folic acid was associated with a reduced risk for delivering offspring with a conotruncal heart defect or a limb deficiency . Data were derived from a population -based case-control study of fetuses and liveborn infants with conotruncal or limb defects among a 1987 - 88 cohort of births in California . Telephone interviews were conducted with mothers of 207 ( 87.0 % of eligible ) conotruncal cases , 178 ( 82.0 % ) limb defect cases , and of 481 ( 76.2 % ) r and omly selected liveborn nonmalformed control infants . Reduced risks were observed for maternal use of multivitamins containing folic acid from one month before until two months after conception . Odds ratios and 95 % confidence intervals for any compared to no multivitamin use were 0.70 ( 0.46 - 1.1 ) for conotruncal defects and 0.64 ( 0.41 - 1.0 ) for limb defects . Controlling for maternal race/ethnicity , age , education , gravidity , alcohol use , and cigarette use result ed in a further reduction to the odds ratio for conotruncal defects , 0.53 ( 0.34 - 0.85 ) , but not for limb defects . Among non-vitamin using women , consumption of cereal containing folic acid was also associated with reduced risk for both defects . Women who take multivitamins have 30 - 35 % lower risk of delivering offspring with either conotruncal or limb defects . This association may not be attributable to folic acid specifically , but may be a consequence of other multivitamin components , or some unknown behaviors that highly correlate with regular use of a multivitamin . However , should the association prove causal , it offers an important opportunity for preventing thous and s of serious birth defects We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population -based case-control study in metropolitan Atlanta . Case infants ( 905 ) with cardiac defects were actively ascertained from multiple sources . Control infants ( 3,029 ) were infants without birth defects who were selected from birth certificates by stratified r and om sampling . We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period . Febrile illness was positively associated with the occurrence of heart defects in the offspring ( odds ratio [ OR ] = 1.8 ; 95 % confidence interval = 1.4–2.4 ) . When influenzalike illness was the reported febrile illness , the OR was 2.1 ( 95 % confidence interval = 0.8–5.5 ) . The association with febrile illness was strongest for tricuspid atresia ( OR = 5.2 ) , left obstructive defects ( OR = 2.7 ) , transposition of the great arteries ( OR = 1.9 ) , and ventricular septal defects ( OR = 1.8 ) . These ORs were generally lower among mothers who used multivitamins during the periconceptional period We studied the association between multivitamin use during the periconceptional period and the occurrence of neural tube defects using data from the Atlanta Birth Defects Case-Control Study . There were 347 babies with neural tube defects who were live born or stillborn to residents of metropolitan Atlanta from 1968 through 1980 . The 2829 control-babies born without birth defects were r and omly selected through birth certificates . Periconceptional multivitamin use was defined as reported use for each of the three months before conception through the first three months of pregnancy . Mothers who reported not using multivitamins any time during the six-month period were defined as nonusers . Fourteen percent of mothers reported periconceptional multivitamin use and 40 % reported nonuse . Multivitamin users were different from nonusers in a number of demographic , health-related , and life-style characteristics . We found an overall apparent protective effect of periconceptional multivitamin use on the occurrence of neural tube defects , with a crude estimated relative risk of 0.40 ( 95 % confidence interval , 0.25 to 0.63 ) . At this time , it is not possible to determine whether this apparently lower risk is the direct result of multivitamin use or the result of other characteristics of women who use multivitamins |
11,117 | 28,902,467 | Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis ( AR ) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post-AIT in addition to its sustained effect on AR symptoms and medication . | Allergic diseases are common and frequently coexist .
Allergen immunotherapy ( AIT ) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects .
The European Academy of Allergy and Clinical Immunology ( EAACI ) has developed a clinical practice guideline to provide evidence -based recommendations for AIT for the prevention of ( i ) development of allergic comorbidities in those with established allergic diseases , ( ii ) development of first allergic condition , and ( iii ) allergic sensitization . | BACKGROUND The natural history of allergic sensitization is complex and poorly understood . A prospect i ve nonr and omized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites ( HDMs ) . OBJECTIVES The study was design ed to determine whether specific immunotherapy ( SIT ) with st and ardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey . METHODS We studied 22 children monosensitized to HDM who were receiving SIT with st and ardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM . The initial investigation included a full clinical history , skin tests with a panel of st and ardized allergens , and the measurement of allergen-specific IgE , depending on the results of skin tests . Children were followed up on an annual basis for 3 years , and the development of new sensitizations in each group was recorded . RESULTS Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group ( p = 0.001 , chi square test ) . CONCLUSIONS This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations BACKGROUND Data on the long-term effects of sublingual immunotherapy ( SLIT ) are sparse , and the optimal duration of treatment is a matter of debate . OBJECTIVE We sought to prospect ively evaluate the long-term effect of SLIT given for 3 , 4 , or 5 years and to compare the effect of those different duration s. METHODS In this prospect i ve open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years . The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3 , 4 , or 5 years . Clinical scores , skin sensitizations , methacholine reactivity , and nasal eosinophil counts were evaluated every year during the winter months . The clinical effect was considered to persist until clinical scores remained at less than 50 % of the baseline value , and then patients underwent another course of SLIT . RESULTS Seventy-eight patients were enrolled , and 59 completed the study . In the 12 control subjects no relevant change in clinical scores was seen throughout the study . In the patients receiving SLIT for 3 years , the clinical benefit persisted for 7 years . In those receiving immunotherapy for 4 or 5 years , the clinical benefit persisted for 8 years . New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT ( 21 % , 12 % , and 11 % , respectively ) . The second course of vaccination induced a benefit more rapidly than the first course . The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score . CONCLUSION Under the present conditions , it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination Background : Although widely practice d for over 80 years , the role of specific immunotherapy ( SIT ) in pediatric asthma treatment is still controversial . We assessed the effects of a 3‐year period of subcutaneous administration of a st and ardized preparation of Dermatophagoides pteronyssinus ( D pt ) on the respiratory health in a group of asthmatic children monosensitized to house dust mite ( HDM ) BACKGROUND Previous studies have suggested that single-allergen-specific immunotherapy ( SIT ) may prevent sensitization to other airborne allergens in monosensitized children . We aim ed to assess the prevention of new sensitizations in monosensitized children treated with single-allergen SIT injections in comparison with monosensitized patients given appropriate pharmacologic treatment for their disease . METHODS A total of 147 children with rhinitis and /or asthma monosensitized to house dust mite were studied ; 45 patients underwent SIT with adsorbed extracts and 40 patients underwent SIT with aqueous extracts for 5 years . The control group was comprised of 62 patients given only pharmacologic treatment for at least 5 years . Skin prick tests , medication scores for rhinitis and asthma , and atopy scores according to skin prick tests were evaluated at the beginning and after 5 years of treatment . RESULTS All groups were comparable in terms of age , sex , and disease characteristics . At the end of 5 years , 64 out of 85 ( 75.3 % ) in the SIT group showed no new sensitization , compared to 29 out of 62 children ( 46.7 % ) in the control group ( P = .002 ) . There were no differences between the SIT subgroups with regard to onset of new sensitization ( P = .605 ) . The patients developing new sensitizations had higher atopy scores ( P = .002 ) and medication scores for both rhinitis ( P = .008 ) and asthma ( P = .013 ) in comparison to patients not developing new sensitizations after 5 years of SIT . CONCLUSION According to our data , SIT has the potential to prevent the onset of new sensitizations in children with rhinitis and /or asthma monosensitized to house dust mite BACKGROUND Sublingual immunotherapy ( SLIT ) has been proved to be effective in allergic rhinitis and asthma , but there are few data on its preventive effects , especially in children . OBJECTIVE To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations , clinical symptoms , and bronchial hyperreactivity . METHODS A total of 216 children with allergic rhinitis , with or without intermittent asthma , were evaluated and then r and omized to receive drugs alone or drugs plus SLIT openly for 3 years . The clinical score was assessed yearly during allergen exposure . Pulmonary function testing , methacholine challenge , and skin prick testing were performed at the beginning and end of the study . RESULTS One hundred forty-four children received SLIT and 72 received drugs only . Dropouts were 9.7 % in the SLIT group and 8.3 % in the controls . New sensitizations appeared in 34.8 % of controls and in 3.1 % of SLIT patients ( odds ratio , 16.85 ; 95 % confidence interval , 5.73 - 49.13 ) . Mild persistent asthma was less frequent in SLIT patients ( odds ratio , 0.04 ; 95 % confidence interval , 0.01 - 0.17 ) . There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year . The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group . Adherence was 80 % or higher in 73.8 % of patients . Only 1 patient reported systemic itching . CONCLUSIONS In everyday clinical practice , SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy Thirty children with rhinoconjunctivitis due to birch pollinosis were treated in a double blind manner for 10 months with enteric‐coated capsules containing either a birch pollen preparation ( n= 14 ) with doses up to 1.4 × 106 biologic units per day or placebo ( n= 16 ) . Compared with the placebo group the actively treated children had less symptoms during the birch pollen season after 3 months of therapy ( P = 0.035 ) . Skin prick reactions decreased significantly more in the active group than in the placebo group after 10 months ( P = 0.01 ) . Conjunctival sensitivity was lower in the active group than in the placebo group after 3 months of treatment ( P = 0.01 ) but not after 10 months . Compared with the placebo group treated children more often increased their levels of IgG ( P= 0.007 ) and pre‐seasonal IgE ( P= 0.001 ) against birch . There was a seasonal increase of IgE antibody level against birch in the placebo but not in the treatment group ( P < 0.001 ) . None of the treated children developed asthma , compared with five of the untreated children . No general reactions occurred and few side effects were seen during the treatment period . We conclude that in children with birch pollinosis oral immunotherapy with high doses of a biologically potent preparation in enteric‐coated capsules is effective , easy to perform , economic and safe BACKGROUND Atopic diseases are among the most common chronic diseases in adolescents , and it is uncertain whether the prevalence of atopic diseases has reached a plateau or is still increasing . The use of the ISAAC ( International Study of Asthma and Allergy in Childhood ) question naire has provided comparable prevalence rates from many countries , whereas studies including clinical examinations and strict diagnostic criteria are scarce . We aim ed to investigate the prevalence of atopic diseases , the pattern of sensitization , and comorbidities at 14 years in a prospect i ve birth cohort . METHODS The children were examined eight times from birth to 14 years . Visits included question naire-based interviews , clinical examination , skin prick test , and specific IgE. RESULTS Follow-up rate at 14 years was 66.2 % . The 12-month prevalence of any atopic disease was high ( 40.3 % ) mostly due to a high prevalence of rhinoconjunctivitis ( 32.8 % ) , whereas the prevalence of asthma was 12.9 % and of atopic dermatitis 8.1 % . In children with at least one atopic disease , 60 % were sensitized , while only 16 % of those without atopic diseases were sensitized . The frequency of sensitization depended on the phenotype . Among children with rhinoconjunctivitis only , rhinoconjunctivitis with concomitant asthma or atopic dermatitis or both 62.5 % , 81.5 % , 70 % , and 100 % , respectively , were sensitized , whereas it was 7.7 % and 33.3 % of children with only asthma or atopic dermatitis . CONCLUSION The prevalence of rhinoconjunctivitis was high in adolescence . Children with rhinoconjunctivitis with and without comorbidities were frequently sensitized . Children with asthma without concomitant allergic rhinoconjunctivitis were rarely sensitized BACKGROUND Allergic rhinitis ( AR ) is a main risk factor for the development of asthma . Two r and omized open-label trials indicated that allergy immunotherapy ( AIT ) prevents the onset of asthma in patients with AR . However , these trials have method ological limitations , and it is unclear to what extent this experimental efficacy translates into clinical effectiveness . OBJECTIVES We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR . METHODS Using routine health care data from German National Health Insurance beneficiaries , we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005 . These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006 . Both groups were observed regarding the risk of incident asthma in 2007 to 2012 . Risk ratios ( RRs ) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age , sex , health care use because of AR , and use of antihistamines . RESULTS In a total of 2431 ( 2.0 % ) patients , AIT was started in 2006 . Asthma was newly diagnosed from 2007 - 2012 in 1646 ( 1.4 % ) patients . The risk of incident asthma was significantly lower in patients exposed to AIT ( RR , 0.60 ; 95 % CI , 0.42 - 0.84 ) compared with patients receiving no AIT in 2006 . Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy ( RR , 0.54 ; 95 % CI , 0.38 - 0.84 ) and AIT including native ( nonallergoid ) allergens ( RR , 0.22 ; 95 % CI , 0.02 - 0.68 ) . AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years . CONCLUSION AIT effectively prevents asthma in patients with AR in a real-world setting . Confounding by indication can not be excluded but would lead to an underestimation of the true preventive effects of AIT BACKGROUND We wondered whether short-term coseasonal sublingual immunotherapy ( SLIT ) can reduce the development of asthma in children with hay fever in an open r and omized study . OBJECTIVE We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever . METHODS One hundred thirteen children aged 5 to 14 years ( mean age , 7.7 years ) with hay fever limited to grass pollen and no other clinical ly important allergies were r and omized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or st and ard symptomatic therapy . All of the subjects had hay fever symptoms , but at the time of study entry , none reported seasonal asthma with more than 3 episodes per season . Symptomatic treatment was limited to cetirizine , loratadine , nasal budesonide , and salbutamol on dem and . The hay fever and asthma symptoms were quantified clinical ly . RESULTS The actively treated children used less medication in the second and third years of therapy , and their symptom scores tended to be lower . From the second year of immunotherapy , subjective evaluation of overall allergy symptoms was favorable in the actively treated children . Development of asthma after 3 years was 3.8 times more frequent ( 95 % confidence limits , 1.5 - 10.0 ) in the control subjects . CONCLUSIONS Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever Summary The present guideline ( S2k ) on allergen-specific immunotherapy ( AIT ) was established by the German , Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology , dermatology and venereology , pediatric and adolescent medicine , pneumology as well as a German patient organization ( German Allergy and Asthma Association ; Deutscher Allergie- und Asthmabund , DAAB ) according to the criteria of the Association of the Scientific Medical Societies in Germany ( Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften , AWMF).AIT is a therapy with disease-modifying effects . By administering allergen extracts , specific blocking antibodies , toler-ance-inducing cells and mediators are activated . These prevent further exacerbation of the allergen-triggered immune response , block the specific immune response and attenuate the inflammatory response in tissue . Products for SCIT or SLIT can not be compared at present due to their heterogeneous composition , nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients . Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed ( depot ) extracts , as well as chemically modified allergens ( allergoids ) as depot extracts . Allergen extracts for SLIT are used in the form of aqueous solutions or tablets . The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints . The EMA stipulates combined symptom and medication scores as primary endpoint . A harmonization of clinical endpoints , e. g. , by using the combined symptom and medication scores ( CSMS ) recommended by the EAACI , is desirable in the future in order to permit the comparison of results from different studies . The current CONSORT recommendations from the ARIA/GA2LEN group specify st and ards for the evaluation , presentation and publication of study results .According to the Therapy allergen ordinance ( TAV ) , preparations containing common allergen sources ( pollen from grasses , birch , alder , hazel , house dust mites , as well as bee and wasp venom ) need a marketing authorization in Germany . During the marketing authorization process , these preparations are examined regarding quality , safety and efficacy . In the opinion of the authors , authorized allergen preparations with documented efficacy and safety , or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA st and ards , should be preferentially used . Individual formulations ( NPP ) enable the prescription of rare allergen sources ( e.g. , pollen from ash , mugwort or ambrosia , mold Alternaria , animal allergens ) for specific immunotherapy . Mixing these allergens with TAV allergens is not permitted . Allergic rhinitis and its associated co-morbidities ( e. g. , bronchial asthma ) generate substantial direct and indirect costs . Treatment options , in particular AIT , are therefore evaluated using cost-benefit and cost-effectiveness analyses . From a long-term perspective , AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy , but is heavily dependent on patient compliance . Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups . Data from controlled studies differ in terms of scope , quality and dosing regimens and require product-specific evaluation . Therefore , evaluating individual preparations according to clearly defined criteria is recommended . A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed . The website of the German Society for Allergology and Clinical Immunology ( www.dgaki.de/leitlinien/s2k-leitlinie-sit ; DGAKI : Deutsche Gesellschaft für Allergologie und klinische Immunologie ) provides tables with specific information on available products for AIT in Germany , Switzerl and and Austria . The tables contain the number of clinical studies per product in adults and children , the year of market authorization , underlying scoring systems , number of r and omized and analyzed subjects and the method of evaluation ( ITT , FAS , PP ) , separately given for grass pollen , birch pollen and house dust mite allergens , and the status of approval for the conduct of clinical studies with these products . Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and , in childhood and adolescence , in a few trials . Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children . Only a few controlled trials , independent of age , are available for mold allergy ( in particular Alternaria ) . With regard to animal d and er allergies ( primarily to cat allergens ) , only small studies , some with method ological deficiencies are available . Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date . SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma ( GINA ) 2007 and intermittent and mild persistent asthma ( GINA 2005 ) and it is recommended as a treatment option , in addition to allergen avoidance and pharmacotherapy , provided there is a clear causal link between respiratory symptoms and the relevant allergen . The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children , whilst its efficacy in tree pollen allergy has only been shown in adults . New controlled trials ( some with high patient numbers ) on house dust mite allergy provide evidence of efficacy of SLIT in adults . Compared with allergic rhinoconjunctivitis , there are only few studies on the efficacy of SLIT in allergic asthma . In this context , newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children , adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults . Aspects of secondary prevention , in particular the reduction of new sensitizations and reduced asthma risk , are important rationale s for choosing to initiate treatment early in childhood and adolescence . In this context , those products for which the appropriate effects have been demonstrated should be considered . SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled ( DBPC ) study . At present , clinical trials are underway for the indication in asthma due to house dust mite allergy , some of the results of which have already been published , whilst others are still awaited ( see the DGAKI table “ Approved/potentially completed studies ” via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit ( according to www . clinical trialsregister.eu ) ) . When establishing the indication for AIT , factors that favour clinical efficacy should be taken into consideration . Differences between SCIT and SLIT are to be considered primarily in terms of contraindications . In individual cases , AIT may be justifiably indicated despite the presence of contraindications . SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction . Patients must be fully informed about the procedure and risks of possible adverse events , and the details of this process must be documented ( see “ Treatment information sheet ” ; available as a h and out via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit ) . Treatment should be performed according to the manufacturer‘s product information leaflet . In cases where AIT is to be performed or continued by a different physician to the one who established the indication , close cooperation is required in order to ensure that treatment is implemented consistently and at low risk . In general , it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials . Treatment adherence among AIT patients is lower than assumed by physicians , irrespective of the form of administration . Clearly , adherence is of vital importance for treatment success . Improving AIT adherence is one of the most important future goals , in order to ensure efficacy of the therapy . Severe , potentially life-threatening systemic reactions during SCIT are possible , but – providing all safety measures are adhered to – these events are very rare . Most adverse events are mild to moderate and can be treated well . Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT . Systemic reactions have been described in SLIT , but are seen far less often than with SCIT . In terms of anaphylaxis and other severe systemic reactions , SLIT has a better safety profile than SCIT.The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel , adhering to safety st and ards and prompt use of emergency measures , including early administration of i. m. epinephrine . Details on the acute management of anaphylactic reactions can be found in the current S2 guideline on anaphylaxis issued by the AWMF ( S2-AWMF-LL Registry Number 061 - 025).AIT is undergoing some innovative developments in many areas ( e. g. , allergen characterization , new administration routes , adjuvants , faster and safer dose escalation protocol s ) , some of which are already being investigated in clinical trials . Cite this as Pfaar O , BACKGROUND Allergen specific immunotherapy is the only specific and curative approach in the treatment of IgE-mediated allergic diseases such as bronchial asthma and allergic rhinitis . The safety and clinical efficacy of this treatment are well documented but data on the prevention of new sensitizations remain scarce . OBJECTIVE To demonstrate the efficacy of specific immunotherapy in allergic respiratory diseases in childhood and to determine whether this treatment prevents the development of new sensitizations in children sensitized to house dust mite or pollen species . METHODS Fifty-six patients received specific immunotherapy ( 43 sensitive to house dust mite and 13 sensitive to pollen ) . Fifty-one patients not receiving immunotherapy but treated with pharmacotherapy were enrolled in the control group . The patients were followed-up for at least 4 years and treatment efficacy and the development of new sensitizations were compared between the two groups . RESULTS The number of patients with symptoms was significantly decreased in both groups at the end of the treatment period . No new sensitizations were found in 35 of the 43 ( 81.39 % ) patients in the house dust mite immunotherapy group and in 10 of 13 ( 76.92 % ) patients in the pollen immunotherapy group . In contrast , 20 of 51 ( 39.21 % ) patients in the control group showed new sensitizations . The difference between the house dust mite and pollen immunotherapy groups and the control group in this parameter was statistically significant ( p = 0.033 ) . CONCLUSION Our data demonstrate that administration of specific immunotherapy in allergic patients significantly reduced symptoms and the development of new sensitivities BACKGROUND Children with allergic rhinitis are likely to develop asthma . OBJECTIVE The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis . METHODS From 6 pediatric allergy centers , 205 children aged 6 to 14 years ( mean age , 10.7 years ) with grass and /or birch pollen allergy but without any other clinical ly important allergy were r and omized either to receive specific immunotherapy for 3 years or to an open control group . All subjects had moderate to severe hay fever symptoms , but at inclusion none reported asthma with need of daily treatment . Symptomatic treatment was limited to loratadine , levocabastine , sodium cromoglycate , and nasal budesonide . Asthma was evaluated clinical ly and by peak flow . Methacholine bronchial provocation tests were carried out during the season(s ) and during the winter . RESULTS Before the start of immunotherapy , 20 % of the children had mild asthma symptoms during the pollen season(s ) . Among those without asthma , the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis ( odds ratio , 2.52 ; P < .05 ) . Methacholine bronchial provocation test results improved significant in the active group ( P < .05 ) . CONCLUSION Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis Background : Limited data exist regarding extended , long-term immunologic effects of immunotherapy in polysensitized individuals . To study possible long-term effects , skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before . Methods : Eighty-two subjects ( 78 % male , mean age 23 years ) previously enrolled in a r and omized , placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood ( mean follow-up interval , 10.8 years ) by puncture skin tests and CAP-RAST levels for major aeroallergens . All completed at least 18 months ( median 27 months ) of maintenance active treatment or placebo injections without subsequent immunotherapy . Results : At adult follow-up , 36 % of all skin tests to treatment allergens among subjects who received immunotherapy ( n = 41 ) had significantly reduced intensity versus 26 % of skin tests among placebo recipients ( n = 41 ; p = 0.03 ) . No significant differences were noted for individual treatment allergens . No significant differences were observed in the long-term changes of serum-specific IgE antibody levels for all treatment allergens between immunotherapy treatment and placebo groups ( p = 0.43 ) . The treatment and placebo groups had a similar acquisition of new skin test sensitivities from time of r and omization in the original childhood trial to debriefing ( 15 vs. 20 % ; p = 0.28 ) and to adult follow-up ( 30 vs. 31 % ; p = 0.75 ) . Conclusions : Immunotherapy suppresses skin test sensitivity 8–16 years after discontinuation of treatment , but long-term effects on specific IgE levels in serum are not observed . Broad-spectrum immunotherapy does not appear to affect the acquisition of new inhalant sensitivities BACKGROUND Allergic rhinoconjunctivitis is a risk factor for asthma development . Treating the underlying allergy may represent an attractive method of asthma prevention . No regulatory guidance exists in this area , and , to our knowledge , no clinical investigations meeting modern regulatory st and ards have been published . OBJECTIVE The objective of this publication is to describe the rationale behind the design of and report on the recruitment for the ongoing pediatric Grazax Asthma Prevention ( GAP ) trial . METHODS The trial was design ed for assessment of the preventive effect of an SQ-st and ardized grass allergy immunotherapy tablet ( AIT ) on asthma development , both during treatment and after the end of treatment . ( The st and ardized quality [ SQ ] procedure is a st and ardization procedure comprising 3 components : total potency , major allergen content , and assessment of extract complexity . ) The trial design was discussed with several European Competent Authorities . RESULTS The GAP trial is a multinational , parallel-group , double-blind , placebo-controlled r and omized trial . Main eligibility criteria were age of 5 to 12 years , grass pollen-induced allergic rhinoconjunctivitis , no asthma , and no overlapping symptomatic allergies . The children have been r and omized 1:1 to receive the grass AIT or placebo once daily for 3 years , followed by a blinded observational period of 2 years . Asthma is assessed by the investigators according to specific diagnostic criteria , used at screening visits before r and omization to exclude children with existing asthma , and evaluated at least half-yearly during the trial . Seven months of screening result ed in 812 r and omized children at 101 centers in 11 countries . CONCLUSIONS To our knowledge , the GAP trial represents the first double-blind , placebo-controlled r and omized trial to assess the preventive effect of allergen-specific immunotherapy on asthma development . A total of 812 children were successfully recruited into the trial . EudraCT number : 2009 - 011235 - 12 While the prevalence of asthma in children is decreasing or remaining the same , time trends in the prevalence of rhinitis in children are not known . Underst and ing sensitisation trends may help inform about trends in asthma and rhinitis prevalence Background Subcutaneous immunotherapy for respiratory allergy has shown a long‐lasting efficacy after its discontinuation , whereas this evidence is still lacking for sublingual immunotherapy , despite the fact that it is widely used BACKGROUND Longitudinal prospect i ve population -based birth cohort studies of the natural history of sensitization and allergic diseases from childhood to adulthood are few . The aim of the present prospect i ve study was to investigate the natural course of sensitization and allergic diseases in a r and om population -based sample of 276 children from a 1-year birth cohort of unselected Danish children followed from birth to 26 years of age . METHODS Question naire-based interviews , physical examination , skin prick tests , specific IgE testing , and from 10 years also spirometry , were carried out at 1.5 , 5 , 10 , 15 and 26 years of age . Predefined diagnostic criteria were used . RESULTS Follow-up rates were high , 193 ( 70 % ) attended the 26-year follow-up . The prevalence of current eczema was stable during childhood ; 13 % ( 1.5 yrs . ) , 9.2 % ( 5 yrs . ) , 10.8 % ( 10 yrs . ) , and 9.8 % ( 15 yrs . ) , and 5.7 % at 26 yrs . From birth to 26 years the cumulative prevalence of eczema , food allergy , asthma , and rhinoconjunctivitis was 23.5 % , 13.8 % , 17 % , and 27.9 % respectively . More than half of the participants had one or more allergic disease in the period between birth and 26 years of age . The rates of sensitization ( S-IgE = 0.35 kU/l ) were 8 % , 23 % , 26 % , 32 % , and 31 % at 1.5 , 5 , 10 , 15 , and 26 years of age , respectively . Sensitization to food allergens was most prevalent in early infancy , whereas sensitization to inhalant allergens dominated later on . CONCLUSION The results support the concept of the allergic march . Allergic diseases are not only occurring in childhood but persist into adulthood Allergic rhinitis can be associated with bronchial hyperresponsiveness ( BHR ) , and carries an increased risk for the development of asthma . The aim of this study was to evaluate the ability of specific immunotherapy ( SIT ) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR . Forty-four subjects monosensitized to Dermatophagoides pteronyssinus , with perennial rhinitis and BHR to methacholine , were r and omly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr . After 1 yr of treatment , a 2.88-fold increase in the provocative dose of methacholine producing a 20 % decrease in FEV(1 ) ( PD(20)FEV(1 ) ) was recorded in the SIT-treated group ( 95 % confidence interval [ CI ] : 3.98- to 2.09-fold ; p < 0.001 ) , with a further increase to fourfold at the end of Year 2 ( 95 % CI : 2.9- to 5.7-fold ; p < 0.001 ) . At the end of the study , the methacholine PD(20)FEV(1 ) was within the normal range in 50 % of treated subjects ( p < 0.0001 ) , and was significantly higher in this group than in the group receiving placebo ( p < 0.0001 ) . In contrast , no changes in methacholine PD(20)FEV(1 ) were found in the placebo group throughout the study . Although 9 % of subjects given placebo developed asthma , none of those treated with SIT did . This study suggests that SIT , when administered to carefully selected , monosensitized patients with perennial allergic rhinitis , reduces airway responsiveness in subjects with rhinitis , and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways BACKGROUND This study aims to examine the immunological parameters , focusing IL-10 productivity , in prophylactic sublingual immunotherapy ( SLIT ) in asymptomatic subjects sensitized to Japanese cedar pollen ( JCP ) . METHODS This study was conducted as part of a r and omized , double-blind , placebo-controlled , multiple center trial , and was performed for two consecutive pollen seasons in 2012 and 2013 . The present results were based only on our institution . We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering . The SLIT group received st and ardized JCP extract for five months over the pollen season . We observed and judged development of the symptoms in the pollen season . The percentage of IL-10 producing CD4(+ ) T ( Trl ) cells , B cells and monocytes were analyzed by flow cytometry . JCP specific IgE and total IgE were also measured . RESULTS The ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013 . In 2012 , the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group . In 2013 , the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group . The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group . CONCLUSIONS Prophylactic SLIT is effective for prevention of the development of pollinosis . Induction of IL-10 producing T cells , B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects OBJECTIVE To evaluate the efficacy of mite allergen specific immunotherapy ( SIT ) to patients of allergic rhinitis . METHOD A total of 102 patients with mite allergy were recruited into the study . They were r and omly divided into two groups : SIT group ( n = 51 ) and ST ( symptomatic therapy ) group ( n = 51 ) . They were given SIT with st and ardized allergen vaccine for 3 years or only symptomatic therapy respectively . Observation items include : rhinitis symptom scores , drug score , skin prick test result , serum specificity IgE ( sIgE ) , peripheral eosinophil counting . The development of asthma and new allergens sensitization was also assessed . RESULT The blood eosinophil numbers , skin test index , rhinitis symptom scores and drug scores were all decreased significantly after the treatment with SIT for 3 years compared to that of ST group ( P < 0.01 ) . Although the level of serum slgE was decreased , no statistic diferences were found . No patients developed asthma in SIT group , and only 2.1 % of patients had new allergen sensitization ; 17.4 % of those in ST group developed asthma , 32.6 % had new sensitization . No severe adverse events occurred . CONCLUSION Keeping long-term SIT is effective and safe for patients with allergic rhinitis induced by mite , which can also prevent new allergen sensitization and development for asthma Allergic rhinitis is often associated with bronchial hyperresponsiveness ( BHR ) and airway inflammation , and it seems to be an important risk factor for the development of asthma . Specific immunotherapy ( SIT ) reduces symptoms and medication requirements in subjects with allergic rhinitis , but the mechanisms by which SIT promotes these beneficial effects are less clear . We have investigated the effects of Parietaria-SIT on rhinitis symptoms , BHR to inhaled methacholine , eosinophilic inflammation and cytokine production ( interferon gamma and interleukin-4 ) in the sputum . The effect on asthma progression was also examined . Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to Parietaria judaica participated in a r and omized , double-blind , placebo-controlled , parallel group study . Participants were r and omly assigned to receive injections of a Parietaria pollen vaccine ( n = 15 ) or matched placebo injections ( n = 15 ) in a rapid updosing cluster regimen for 7 weeks , followed by monthly injections for 34 months . Throughout the 3-year study we collected data on symptoms and medication score , airway responsiveness to methacholine , eosinophilia and soluble cytokines in sputum , followed by a complete evaluation of the clinical course of atopy . Hay fever symptom and medication scores were well controlled by SIT . By the end of the study , in the placebo group , symptom and medication scores significantly increased by a median ( interquartile range ) of 121 % ( 15 - 280 % ) and 263 % ( 0 - 4400 % ) respectively ( p < 0.01 ) , whereas no significant difference was observed in the SIT group . We found no significant changes in the sputum parameters and methacholine PC15 values in both groups throughout the study . By the end of the investigation , a total of 9 out of 29 participants developed asthma symptoms ; of these , seven ( 47 % ) belonged to the placebo group , whereas only 2 ( 14 % ) to the SIT-treated group ( p = 0.056 ) . In conclusion , Parietaria-SIT is effective in controlling hay fever symptoms and rescue medications , but no changes in the BHR to methacholine or sputum eosinophilia were observed . Moreover , Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma , suggesting that SIT should be considered earlier in the management of this condition Background : Some aspects of sublingual immunotherapy ( SLIT ) still need to be addressed : magnitude of the clinical efficacy , effect on the bronchial hyperreactivity adherence to treatment , preventive effect . We attempted to clarify these points in a r and omized open , controlled , two parallel group study in a real‐life setting BACKGROUND Prevention of new IgE sensitizations has been described during allergen-specific immunotherapy . However , prospect i ve data using a preventive approach in very young children who would benefit most are missing . We initiated a prospect i ve pilot study investigating the safety , immunomodulatory , and sensitization-preventive effect of sublingual immunotherapy ( SLIT ) in mono/oligoclonally sensitized , clinical ly asymptomatic children 2 - 5 yr of age . METHODS In this double-blinded , r and omized , placebo-controlled pilot study , 31 mono-/oligosensitized children to house-dust mite or grass pollen were included . SLIT with the respective source ( n = 15 ) or placebo ( n = 16 ) was applied . After dose-up-phase therapy was continued for 2 yr . Parents recorded clinical events , vaccinations , and drug intake in a diary . Skin prick testing and specific IgE and IgG measurements were recorded at baseline , 12 and 24 months . At the same time , allergen-specific proliferation and IL10- and TGFβ-dependent Treg function were measured . RESULTS Preventive application of SLIT in young children was safe ( no relevant side effects in 21,170 single applications ) . After 12 and 24 months of treatment , the rate of allergen-specific sensitization ( specific IgE and SPT reactivity ) was comparable in the treatment and the placebo group . However , verum-treated patients displayed a significant up-regulation of allergen-specific IgG ( p < 0.05 ) . Furthermore , IL10-dependent inhibition ( p < 0.05 ) was observed in vitro in the treatment group but not in the placebo group . CONCLUSION Preventive SLIT is safe in children 2 - 5 yr of age and induces regulatory mechanisms involving allergen-specific IgG and IL10 . Based on this pilot study , large-scale trials will need to investigate the modulation of sensitization and clinical ly relevant allergy BACKGROUND Children born to atopic parents are at increased risk of sensitization to environmental allergens . OBJECTIVE We sought to demonstrate proof of concept for oral immunotherapy to high-dose house dust mite ( HDM ) allergen in infancy in the prevention of allergen sensitization and allergic diseases . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled , proof-of-concept study involving 111 infants less than 1 year of age at high risk of atopy ( ≥ 2 first-degree relatives with allergic disease ) but with negative skin prick test responses to common allergens at r and omization . HDM extract ( active ) and appropriate placebo solution were administered orally twice daily for 12 months , and children were assessed every 3 months . Co primary outcomes were cumulative sensitization to HDM and sensitization to any common allergen during treatment , whereas development of eczema , wheeze , and food allergy were secondary outcomes . All adverse events were recorded . RESULTS There was a significant ( P = .03 ) reduction in sensitization to any common allergen ( 16.0 % ; 95 % CI , 1.7 % to 30.4 % ) in the active ( 5 [ 9.4 % ] ) compared with placebo ( 13 [ 25.5 % ] ) treatment groups . There was no treatment effect on the co primary outcome of HDM sensitization and the secondary outcomes of eczema , wheeze , and food allergy . The intervention was well tolerated , with no differences between active and placebo treatments in numbers or nature of adverse events . CONCLUSION Prophylactic HDM oral immunotherapy is well tolerated in children at high heredity risk . The results met the trial 's prespecified criteria for proof of concept in reducing sensitization to any allergen ; however , no significant preventive effect was observed on HDM sensitization or allergy-related symptoms BACKGROUND Safety data on ' real-life ' allergen immunotherapy ( AIT ) in children and adolescents is usually extrapolated from studies in adults . METHODS Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospect i ve European survey . Patient profiles and systemic reactions ( SRs ) were recorded . Descriptive , univariate and multivariate analyses were used to identify risk factors for SRs . RESULTS A total of 1563 patients ( mean ± SD age : 11.7 ± 3.9 years ; rhinitis : 93.7 % ; asthma : 61.5 % ; polysensitization : 62.5 % ) and 1578 courses of AIT were assessed . Single-allergen AIT was administered in 89.5 % of cases ( n = 1412 ; mites : 49 % ; grass pollen : 25.8 % ; tree pollen : 8.7 % ; Alternaria : 4.6 % ; d and er : 0.8 % ; weed pollen : 0.6 % ) . Subcutaneous AIT ( SCIT ) was used in 71.4 % ( n = 1127 ) of the treatments , including 574 ( 50.9 % ) with natural extracts . Sublingual AIT ( SLIT ) was used for the remaining 451 treatments ( drops : 73.8 % ; tablets : 26.2 % ) . The mean ± SD follow-up period was 12.9 ± 3.3 months . The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT . Twenty-four patients ( 1.53 % ) experienced 29 SRs . Respiratory ( 55.7 % ) and skin symptoms ( 37.9 % ) were most frequent . Anaphylaxis was diagnosed in 3 SRs ( 10.3 % ) , and adrenaline was administered in 2 of these cases . In a univariate analysis , the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization ( > 3 ) , grass pollen extracts and the use of natural extracts ( vs. allergoids ) . CONCLUSIONS In a real-life paediatric setting , AIT is safe . SRs are infrequent and generally not severe . Pollen polysensitization , grass pollen extracts and natural extracts ( vs. allergoids ) were risk factors for AIT-associated SRs |
11,118 | 24,271,462 | Notwithst and ing , it may be tentatively inferred that cross-sectional imaging has a therapeutic impact in the more challenging cases .
In terms of impact , this review has found no evidence to support any specific imaging modality when planning dental implant placement in any region of the mouth . | The objectives for this systematic review were to determine if the pre-operative availability of cross-sectional imaging , such as cone beam CT , has a diagnostic impact , therapeutic impact or impact on patients ' outcome when placing two dental implants in the anterior m and ible to support an overdenture . | OBJECTIVE To compare panoramic and conventional cross-sectional tomography for preoperative selection of implant size for three implant systems ( Brånemark , Straumann ( ® ) , 3i ) . MATERIAL AND METHODS Presurgical panoramic ( Pan ) and cross-sectional tomograms ( Tomo ) of 121 implant sites in 121 patients scheduled for single-tooth implant treatment were recorded ; in 70 of the Pans ( Pan-B ) , a metal ball was placed in the edentulous area . By means of dedicated software , an implant with subjectively determined proper dimensions for the respective site was outlined by manually placing four reference points in each image by three observers . Additionally , four reference points corresponding to the margins of the metal ball were manually placed in Pan-Bs . The length and width of the implant were calculated after calibration to the reference ball ( true magnification ) in Pan-Bs and to a " st and ard " calibration method in all images ( magnification factor 1.25 in Pans and 1.7 in Tomos ) . Based on the corrected dimensions , the nearest , smaller implant size was selected among those available in each of the three implant systems . RESULTS When comparing Pans with Tomos , selected implant size differed in on average 89 % of the cases . The length differed in 69 % and the width in 66 % . Implants planned on Tomos were longer than those planned on Pans in 47 % and narrower in 30 % ( < 10 % in posterior regions ) . The Straumann ( ® ) system , with the smallest range of available implant sizes was significantly less affected by the radiographic method compared with the other two systems . CONCLUSION The selected implant size differed considerably when planned on panoramic or cross-sectional tomographs OBJECTIVE To investigate whether cross-section imaging influences the planning and therapy of st and ard implant cases in the posterior m and ible . MATERIAL AND METHODS In a prospect i ve study conducted over 16 months , the planned treatment ( st and ard implant therapy without bone augmentation procedures in the premolar and molar regions of the m and ible ) was compared with the postoperative result in 50 r and omly selected patients . Clinical examinations and panoramic radiographs were performed pre- and postoperatively , whereas cross-sectional tomography was performed only preoperatively . RESULTS The vertical magnification factor in the panoramic radiographs was very constant pre- and postoperatively with 1 : 1.27 and in the spiral tomograms with 1 : 1.52 . In 11 of 77 implant sites , the m and ibular canal could not be evaluated in the spiral tomograms . The additional information from cross-sectional spiral tomography did not influence the original planning in 74 of 77 ( 96.1 % ) implant sites . Based on the postoperative panoramic radiograph , the average distance from the tip of the implants to the m and ibular canal was 3.04+/-2.06 mm . In two cases ( 2.6 % ) , transient postoperative altered tactile sensation of the mental nerve was found . CONCLUSION The information from preoperative cross-sectional spiral tomography has minor impact on treatment planning in st and ard implant cases in m and ibular premolar and molar regions . The clinical examination provides sufficient information for selecting implant diameter and the panoramic radiograph provides sufficient information for implant length selection PURPOSE To establish a basis for weighing the potential diagnostic and therapeutic benefits of three-dimensional cone-beam ( CB ) data sets in contrast to digital orthopantomography ( OPG ) and computerized tomography ( CT ) in implant dentistry . MATERIAL S AND METHODS Twenty-seven patients requiring implant surgery received a single presurgical CB scan . A follow-up digital OPG was taken within a maximal postsurgical period of 2 weeks . For comparison purpose s , a control group of 29 patients receiving CT as well as CB diagnosis was analyzed . Image quality of the different modalities was ranked retrospectively by five experienced examiners ( from excellent to insufficient ) for up to 10 defined criteria , including general image quality and several specific structures . The results were analyzed statistically , and interobserver agreement was calculated using intraclass correlation coefficients ( ICCs ) . RESULTS The median rating for all investigated criteria was good for CB imaging and between good and insufficient for OPG in the dental implant group . Except for general image quality , statistical analysis showed that CB imaging was significantly superior to OPG imaging for all investigated anatomic structures . With a few exceptions , all investigated anatomic structures in CT and CB imaging were rated excellent in the control group . No significant difference between CT and CB imaging was detected in the control group for all investigated criteria . With a few exceptions , ICCs were higher for CB images than for OPG . In the control group , ICCs for CT and CB images were similar , with a few exceptions . CONCLUSION The results of the present study confirm superior radiographic visualization for all important high-contrast structures in presurgical implant dentistry assessment for CB imaging in contrast to OPG and a CT-like degree of information for high-contrast structures in CB data sets . Clinical ly , however , the elevated radiation dosages transmitted by CB imaging must be taken into account |
11,119 | 27,042,115 | Conclusion Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients .
Our findings support the use of pemetrexed plus platinum doublet regimen as first-line treatment in advanced nonsquamous NSCLC patients because of its potential survival benefits | Purpose To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer ( NSCLC ) through a trial-level meta- analysis . | BACKGROUND Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits lig and binding . We aim ed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) . METHODS We did this r and omised , open-label , controlled phase 3 study at 103 sites in 20 countries . Patients aged 18 years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 2 and adequate organ function , were r and omly assigned 1:1 to treatment with a block r and omisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system . Patients received either cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 of a 3-week cycle for a maximum of six cycles alone , or with necitumumab 800 mg on days 1 and 8 . Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects . R and omisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region . Patients and study investigators were not masked to group assignment . The primary endpoint was overall survival . Efficacy analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00982111 . FINDINGS Between Nov 11 , 2009 , and Feb 2 , 2011 , we r and omly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin ( n=315 ) or pemetrexed and cisplatin alone ( n=318 ) . Enrolment was stopped on Feb 2 , 2011 , after a recommendation from the independent data monitoring committee . There was no significant difference in overall survival between treatment groups , with a median overall survival of 11·3 months ( 95 % CI 9·5 - 13·4 ) in the necitumumab plus pemetrexed and cisplatin group versus 11·5 months ( 10·1 - 13·1 ) in the pemetrexed and cisplatin group ( hazard ratio 1·01 [ 95 % CI 0·84 - 1·21 ] ; p=0·96 ) . The incidence of grade 3 or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in 15 ( 5 % ) of 304 patients in the necitumumab group versus nine ( 3 % ) of 312 patients in the pemetrexed and cisplatin group . Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( 155 [ 51 % ] of 304 vs 127 [ 41 % ] of 312 patients ) . Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3 - 4 rash ( 45 [ 15 % ] of 304 vs one [ < 1 % ] of 312 patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( 23 [ 8 % ] vs seven [ 2 % ] patients ) , and grade 3 or higher venous thromboembolic events ( 23 [ 8 % ] vs 11 [ 4 % ] patients ) than did those in the pemetrexed and cisplatin alone group . INTERPRETATION Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC . Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin . FUNDING Eli Lilly and Company Introduction : This study compared survival without toxicity in patients with advanced , nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin . Methods : This multicenter , open-label , parallel-group , phase 3 trial comprised patients r and omized ( 1:1 ) to pemetrexed/carboplatin ( n = 128 ) or docetaxel/carboplatin ( n = 132 ) . Patients received treatment on day 1 of each 21-day cycle ( maximum of six cycles ) . Treatment included carboplatin ( area under the curve = 5 mg/ml × min ) and pemetrexed ( 500 mg/m2 ) or docetaxel ( 75 mg/m2 ) . The primary outcome measure , survival without treatment-emergent grade 3/4 toxicity , was defined as the time from r and omization to the first treatment-emergent grade 3/4 adverse event or death and was analyzed using a log-rank test . The analysis population included 106 patients in the pemetrexed/carboplatin ( Pem/Carb ) group and 105 patients in the docetaxel/carboplatin ( Doc/Carb ) group . Results : Survival without treatment-emergent grade 3/4 toxicity was significantly longer in the Pem/Carb versus the Doc/Carb group ( log-rank p < 0.001 ; median survival without treatment-emergent grade 3/4 toxicity : 3.2 versus 0.7 months ; adjusted hazard ratio = 0.45 [ 95 % confidence interval : 0.34–0.61 ] ) . Overall survival was similar in the Pem/Carb versus the Doc/Carb group ( log-rank p = 0.934 ; median survival : 14.9 versus 14.7 months ; adjusted hazard ratio = 0.93 [ 95 % confidence interval : 0.66–1.32 ] ) . Compared with the Doc/Carb group , fewer patients in the Pem/Carb group experienced grade 3/4 drug-related , treatment-emergent neutropenia , leukopenia , or febrile neutropenia , and more patients experienced anemia and thrombocytopenia . There were three study drug-related deaths during treatment in each group . Conclusions : The favorable benefit-to-risk profile of pemetrexed/carboplatin suggests that pemetrexed/carboplatin is an appropriate first-line treatment option for chemonaïve patients with advanced , nonsquamous non-small cell lung cancer Background Subgroup analyses of r and omized studies have consistently shown that pemetrexed is exclusively effective in non-small-cell lung cancer ( NSCLC ) other than squamous cell carcinoma and the combination of pemetrexed and platinum agents is recommended for first-line chemotherapy in advanced non-squamous NSCLC ; however , there have been few prospect i ve studies of a selected population . Patients and methods This was a single-arm phase II study of carboplatin and pemetrexed in Japanese patients with chemo-naive advanced non-squamous NSCLC . Patients received six cycles of pemetrexed ( 500 mg/m2 ) combined with carboplatin ( area under the curve : AUC 6 ) every 3 weeks . Maintenance chemotherapy with pemetrexed was permitted in patients whose disease did not progress after combination chemotherapy . The primary endpoint was the response rate , and secondary endpoints were safety and survival . Results Fifty-one patients were enrolled between November 2009 and March 2011 , and 49 patients were evaluable for both safety and efficacy . All but one patient had adenocarcinoma histology . Forty-four ( 90 % ) patients completed four cycles , and 33 ( 67 % ) completed six cycles of chemotherapy . Partial response was achieved in 25 patients ( response rate : 51 % ) and stable disease in 18 patients ( 37 % ) . Median progression-free survival ( PFS ) and overall survival ( OS ) were 6.3 months and 24.3 months , respectively . The median PFS and OS were 7.9 months and 24.3 months in patients with epidermal growth factor receptor ( EGFR ) mutation , and 6.3 months and 21.0 months in patients with EGFR wild type or unknown . There were no statistical differences between EGFR mutants and non-mutants for both PFS ( p = 0.09 ) and OS ( p = 0.23 ) . Grade 3/4 neutropenia and thrombocytopenia were observed in 16 ( 33 % ) and 9 ( 18 % ) patients , respectively . Non-hematologic toxicities were generally mild , and there were no treatment-related deaths . Conclusions The combination of carboplatin and pemetrexed was safe and effective in advanced non-squamous NSCLC . Although the sample size was small , our results indicate that pemetrexed is a key drug for advanced non-squamous NSCLC , irrespective of the EGFR mutation status ( UMIN-CTR number 000002451 ) Background The efficacy and safety of axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non – small-cell lung cancer ( NSCLC ) . Methods Overall , 170 patients were r and omly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of up to six 21-day cycles ( arm I ) ; axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin ( arm II ) ; or pemetrexed/cisplatin alone ( arm III ) . The primary endpoint was progression-free survival ( PFS ) . Results Median PFS was 8.0 , 7.9 , and 7.1 months in arms I , II , and III , respectively ( hazard ratio : arms I vs. III , 0.89 [ P = 0.36 ] and arms II vs. III , 1.02 [ P = 0.54 ] ) . Median overall survival was 17.0 months ( arm I ) , 14.7 months ( arm II ) , and 15.9 months ( arm III ) . Objective response rates ( ORRs ) for axitinib-containing arms were 45.5 % ( arm I ) and 39.7 % ( arm II ) compared with 26.3 % for pemetrexed/cisplatin alone ( arm III ) . Gastrointestinal disorders and fatigue were frequently reported across all treatment arms . The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms ( 20 % and 17 % , arms I and II , respectively ) and fatigue with pemetrexed/cisplatin alone ( 16 % ) . Conclusion Axitinib in combination with pemetrexed/cisplatin was generally well tolerated . Axitinib combinations result ed in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC.Trial registration Clinical Trials.gov : NCT00768755 ( October 7 , 2008 ) BACKGROUND Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer ( NSCLC ) histology . We further review ed the differential efficacy of pemetrexed according to histology in two large , phase III NSCLC trials . METHODS One study tested pemetrexed versus docetaxel in previously treated patients ( n = 571 ) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients ( n = 1,725 ) with advanced NSCLC . Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions ( THIs ) for overall survival ( OS ) and progression-free survival ( PFS ) . For each histologic subgroup , the Kaplan-Meier method was used to estimate unadjusted within-arm medians , and Cox models were used to estimate covariate-adjusted between-arm hazard ratios ( HRs ) . RESULTS In both studies , treatment arms were well balanced for histology . THIs were statistically significant ( p < .005 ) for both OS and PFS . Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators ( HR , 0.78 and 0.84 , respectively ) , whereas squamous patients had shorter survival ( HR , 1.56 and 1.23 , respectively ) . Whereas the efficacy of pemetrexed regimens differed according to histology , it did not differ for docetaxel or for cisplatin plus gemcitabine . Pemetrexed was well tolerated across histologic groups . CONCLUSIONS The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology . These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma , but , because of efficacy and safety advantages , pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC BACKGROUND Although pemetrexed/cisplatin ( P-C ) is a st and ard treatment for advanced non-squamous non-small cell lung cancer ( Nsq-NSCLC ) , neither its efficacy nor the effects of potential differences between driver mutations , such as the anaplastic lymphoma kinase ( ALK ) translocation and epidermal growth factor receptor ( EGFR ) mutations , have been thoroughly examined . PATIENTS AND METHODS A single-arm phase II study of P-C was conducted in Japanese patients with chemo-naïve advanced Nsq-NSCLC . Patients received four cycles of pemetrexed ( 500 mg/m(2 ) ) combined with cisplatin ( 75 mg/m(2 ) ) on day 1 every three weeks . The primary end-point was the response rate ( RR ) and the secondary end-points were toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . RESULTS A total of 50 patients were analyzed ( males , 68 % ; adenocarcinoma , 80 % ) . The RR was 44.0 % . The median PFS and OS were 4.3 months and 22.2 months , respectively . Toxicities were mild , and no new toxicity profiles were identified . Among the 39 out of 50 sample s , six ( 15.4 % ) presented ALK translocation and nine ( 23.1 % ) presented EGFR mutations ; of the remaining patients , 24 ( 61.5 % ) were wild-type for both ALK and EGFR . Objective response was observed in two out of six patients with ALK translocations , six out of nine with EGFR mutations , and in 11 ( 45.8 % ) wild-type patients . CONCLUSION The combination of pemetrexed and cisplatin was effective and safe in Japanese patients with Nsq-NSCLC . We did not observe obvious differences in the efficacy of P-C between patients with ALK translocation or EGFR mutation and those with wild-type genotype PURPOSE To compare pemetrexed/carboplatin with a st and ard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC . PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were r and omly assigned to receive pemetrexed 500 mg/m(2 ) plus carboplatin area under the curve ( AUC ) = 5 ( Calvert 's formula ) on day 1 or gemcitabine 1,000 mg/m(2 ) on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles . The primary end point was health-related quality of life ( HRQoL ) defined as global quality of life , nausea/vomiting , dyspnea , and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the lung cancer-specific module LC13 during the first 20 weeks . Secondary end points were overall survival and toxicity . Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006 . Patients who completed the baseline question naire were analyzed for HRQoL ( n = 427 ) , and those who received > or = one cycle of chemotherapy were analyzed for toxicity ( n = 423 ) . Compliance of HRQoL question naires was 87 % . There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms ( pemetrexed/carboplatin , 7.3 months ; gemcitabine/carboplatin , 7.0 months ; P = .63 ) . The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin , including leukopenia ( 46 % v 23 % , respectively ; P < .001 ) , neutropenia ( 51 % v 40 % , respectively ; P = .024 ) , and thrombocytopenia ( 56 % v 24 % , respectively ; P < .001 ) . More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets , whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms . CONCLUSION Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care PURPOSE To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life ( QoL ) in advanced non-small-cell lung cancer ( NSCLC ) compared with vinorelbine plus cisplatin as first-line chemotherapy . PATIENTS AND METHODS Patients ( n = 1,218 ) with stage IIIB to IV NSCLC were r and omly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks ( VC ) . RESULTS Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients ( P = .044 ; hazard ratio , 1.183 [ 97.2 % confidence interval , 0.989 to 1.416 ] ) . The 2-year survival rate was 21 % for DC-treated patients and 14 % for VC-treated patients . Overall response rate was 31.6 % for DC-treated patients v 24.5 % for VC-treated patients ( P = .029 ) . Median survival ( 9.4 v 9.9 months [ for VC ] ; P = .657 ; hazard ratio , 1.048 [ 97.2 confidence interval , 0.877 to 1.253 ] ) and response ( 23.9 % ) with DCb were similar to those results for VC . Neutropenia , thrombocytopenia , infection , and febrile neutropenia were similar with all three regimens . Grade 3 to 4 anemia , nausea , and vomiting were more common ( P < .01 ) with VC than with DC or DCb . Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients , who experienced deterioration in QoL. CONCLUSION DC result ed in a more favorable overall response and survival rate than VC . Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC . These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC Current pemetrexed/platinum chemotherapy does not produce a satisfactory therapeutic response in advanced lung cancer patients . The aim of this study was to determine whether the administration of gefitinib , a tyrosine kinase inhibitor ( TKI ) , intercalated with pemetrexed/platinum could improve the efficacy in chemotherapy-naïve patients with advanced non-squamous NSCLC without subsequent gefitinib maintenance therapy . Treatment-naïve patients with stage IIIB or IV NSCLC were r and omly assigned to receive pemetrexed ( 500 mg/m2 d1 ) and either cisplatin ( 75 mg/m2 d1 ) or carboplatin ( AUC = 5 d1 ) plus gefitinib ( 250 mg/d on days 3 to 16 of a 3-week cycle ) ( PC-G ) or pemetrexed – platinum ( PC ) alone . R and omization was stratified according to the tobacco smoking status and EGFR mutational status of the patients . The primary endpoint was the non-progression rate ( NPR ) at 12 weeks . Secondary endpoints included progression-free survival ( PFS ) , overall response rate ( ORR ) , overall survival ( OS ) , and biosafety . The NPR at 12 weeks was 84.5 % for the PC-G treatment arm and 83.1 % for the PC treatment arm ( P = 0.87 ) . Median PFS was 7.9 months for the PC-G arm and 7.0 months for the PC arm ( P = 0.57 ) . The ORR was 50.0 % for the PC-G arm and 47.4 % for the PC arm ( P = 0.78 ) . Median survival was 25.4 mo for the PC-G arm and 20.8 mo for the PC arm ( P = 0.54 ) . The incidence of adverse events was similar between the two treatment arms , except for a higher incidence of skin rash with PC-G. Predefined subgroup analyses demonstrated that PC-G significantly increased the PFS compared with the PC regimen in patients with EGFR mutations ( P = 0.017 ) . Although gefitinib intercalated with pemetrexed/platinum chemotherapy did not improve the NPR at 12 weeks compared with chemotherapy , an improvement in the PFS for the intercalated treatment arm was seen in the subgroup of patients with EGFR mutations PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type |
11,120 | 31,286,876 | Accepting and implementing this nontraditional approach by both patients and clinicians can yield measurable improvements in patient trust , patient perception of quality of care and quality of life , and relevant biophysical measurements of clinical parameters . | Background Shared medical appointments ( SMAs ) , or group visits , are a healthcare delivery method with the potential to improve chronic disease management and preventive care .
In this review , we sought to better underst and opportunities , barriers , and limitations to SMAs based on patient experience in the primary care context .
Conclusions SMAs in a variety of formats are increasingly employed in primary care setting s , with no singular gold st and ard . | Background : The need to provide high quality prenatal care services , which take account of women ’s views and specifically address their need for information , support and communication , has been advocated and group prenatal care , had been suggested as one of the ways to achieve this objective . The purpose of this study was to examine the impact of group versus individual prenatal care on satisfaction and prenatal care use . Methods : This was a cluster-r and omized controlled trial with the health center as the r and omization unit that conducted in 2007 . Satisfaction was measured through a st and ardized question naire , and the Kotelchuck Adequacy of Prenatal Care Utilization Index was used to measure prenatal care utilization . Results : We recruited 678 women ( group prenatal care , ( N= 344 ) and individual prenatal care , ( N=334 ) in the study . Women in group prenatal care model were more satisfied than women in individual prenatal care model in all areas evaluated , including information , communication , co-ordination and quality of care . Group care women were significantly more likely to have adequate prenatal care than individual care women were ( OR=1.35 95 % CI=1.26–1.44 ) . Conclusions : Group prenatal care was associated with a significant improvement in client satisfaction and prenatal care utilization . This model of care has implication s for the planning and provision of prenatal services within public health system , which is moving toward a better quality health care , and increasing use of services OBJECTIVE To study time course changes in knowledge , problem solving ability , and quality of life in patients with type 2 diabetes managed by group compared with individual care and education . RESEARCH DESIGN AND METHODS We conducted a 5-year r and omized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit . There were 120 patients with non-insulin-treated type 2 diabetes enrolled and r and omly allocated to group or individual care . Eight did not start and 28 did not complete the study . The main outcome measures were knowledge of diabetes , problem solving ability , quality of life , HbA1c , BMI , and HDL cholesterol . RESULTS Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects ( P<0.001 for both ) . Quality of life improved from year 2 with group care but worsened with individual care ( P<0.001 ) . HbA1c level progressively increased over 5 years among control subjects ( + 1.7 % , 95 % CI 1.1 - 2.2 ) but not group care patients ( + 0.1 % , -0.5 to 0.4 ) , in whom BMI decreased ( -1.4 , -2.0 to -0.7 ) and HDL cholesterol increased ( + 0.14 mmol/l , 0.07 - 0.22 ) . CONCLUSIONS Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and setting s tailored to their needs . Traditional one-to-one care , although delivered according to optimized criteria , is associated with progressive deterioration of knowledge , problem solving ability , and quality of life . Better cognitive and psychosocial results are associated with more favorable clinical outcomes PURPOSE this study was conducted to evaluate the feasibility and acceptability of a managed-care approach ( group visits ) on delivering care to uninsured or inadequately insured patients with type 2 diabetes . METHODS One hundred twenty patients with uncontrolled type 2 diabetes were r and omly assigned to receive care in group visits or usual care for 6 months . At baseline , 3 months , and 6 months , the feasibility and acceptability of this model of healthcare delivery were assessed through the patients ' responses to the Primary Care Assessment Tool and the Trust in Physician Scale . Attendance records were kept for each group . RESULTS Patients who received care in group visits showed an improved sense of trust in their physician compared with patients who continued to receive usual care . There was a tendency for patients in groups to report better coordination of their care , better community orientation , and more culturally competent care . Patient attendance at the groups also indicated good acceptance of this form of healthcare delivery . CONCLUSIONS Group visits were feasible and acceptable to these uninsured and inadequately insured patients with uncontrolled type 2 diabetes and fostered an improved sense of trust in their physician PURPOSE The purpose of the study was to evaluate perceptions of care delivered through group visits to disadvantaged patients with type 2 diabetes . METHODS One hundred eighty-six patients with uncontrolled type 2 diabetes were r and omly assigned to receive care in group visits or usual care for 12 months . Their perceptions of the care they received were measured at baseline and 6 and 12 months by the Primary Care Assessment Tool ( PCAT ) , the Diabetes-Specific Locus of Control ( DLC ) survey , and the Trust in Physician Scale ( TPS ) . RESULTS Compared to patients in usual care , group visit patients ' PCAT scores were higher in the domains of ongoing care ( P = .001 ) , community orientation ( P < .0001 ) , and cultural competence ( P = .022 ) . In addition , group patients had higher scores for the Powerful-Other Health Professional subscale of the DLC survey ( P = .010 ) . CONCLUSIONS Patients assigned to group visits had generally more positive perceptions about their care in the areas of ongoing care , community orientation of care , and cultural competence of care than did those in usual care . The perception that one 's health professional is powerful , however , has been associated with a reluctance of patients to make medication changes on their own in previous studies . These findings suggest the need for modification in the way that group visits are conducted to empower and activate patients while still delivering continuous , culturally competent , and community-oriented care OBJECTIVE We investigated the perceptions of diabetes care and diabetes in patients followed long-term by group or usual care . RESEARCH DESIGN AND METHODS Three open questions were administered to 120 patients ( 43 with T1DM and 77 with T2DM ) who had been r and omized at least 2 years before to be followed by group care and 121 ( 41 T1DM and 80 T2DM ) who had always been on usual care . The responses were analyzed by propositional analysis , by identifying the focal nuclei , i.e. , the terms around which all sentences are organized , and then other predicates , according to their hierarchical relationship to the nuclear proposition . Specific communicative units were arbitrarily classified into three categories : attitudes , empowerment , and locus of control . RESULTS Patients on group care showed more positive attitudes , higher sense of empowerment , and more internal locus of control than those on usual care . In addition , they expressed a wider and more articulated range of concepts associated with the care received and made less use of medical terminology ( P < 0.001 , all ) . Higher HbA1c was associated with negative attitudes ( P = 0.025 ) and negative empowerment ( P = 0.055 ) . CONCLUSIONS Group treatment reinforces communication and peer identification and may achieve its clinical results by promoting awareness , self-efficacy , positive attitudes toward diabetes and the setting of care , an internal locus of control , and , ultimately , empowerment in the patients OBJECTIVES To compare the effectiveness of Cooperative Health Care Clinic ( ( CHCC ) group outpatient model for chronically ill , older health maintenance organization ( HMO ) patients ) with usual care . DESIGN Two-year , r and omized , controlled trial conducted with recruitment from February 1995 through July of 1996 . SETTING Nonprofit group model HMO . PARTICIPANTS Two hundred ninety-four adults ( 145 intervention and 149 usual care ) , aged 60 and older ( mean age 74.1 ) with 11 or more outpatient visits in the prior 18 months , one or more self-reported chronic conditions , and expressed interest in participating in a group clinic . INTERVENTION Monthly group meetings held by patients ' primary care physicians . MEASUREMENT Differences in clinic visits , inpatient admissions , emergency room visits , hospital outpatient services , professional services , home health , and skilled nursing facility admissions ; measures of patient satisfaction , quality of life , self-efficacy , and activities of daily living ( ADLs ) . RESULTS Outpatient , pharmacy services , home health , and skilled nursing facility use did not differ between groups , but CHCC patients had fewer hospital admissions ( P=.012 ) , emergency visits ( P=.008 ) , and professional services ( P=.005 ) . CHCC patients ' costs were $ 41.80 per member per month less than those of control patients . CHCC patients reported higher satisfaction with their primary care physician ( P=.022 ) , better quality of life ( P=.002 ) , and greater self-efficacy ( P=.03 ) . Health status and ADLs did not differ between groups . CONCLUSION The CHCC model result ed in fewer hospitalizations and emergency visits , increased patient satisfaction , and self-efficacy , but no effect on outpatient use , health , or functional status BACKGROUND AND AIMS We showed that continuing education can be embedded into routine diabetes care by seeing patients in small groups rather than individually . Group care was cost-effective in improving quality of life , knowledge of diabetes , health behaviours and clinical outcomes in people with type 2 diabetes . The aim of this study was to verify if group care can also be applied to type 1 diabetes . METHODS AND RESULTS R and omized , controlled clinical trial comparing 31 patients managed by group care with 31 managed by traditional one-to-one care . A syllabus was built and later remodulated with the patients in a series of focus-group meetings . The primary end-point was changes in quality of life . Secondary end-points were : knowledge of diabetes , health behaviours , HbA1c and circulating lipids . Differential costs to the Italian National Health System and to the patients were also calculated . After 3 years , quality of life improved among patients on group care , along with knowledge and health behaviours ( p<0.001 , all ) . Knowledge added its effects to those of group care by independently influencing behaviours ( p=0.004 ) while quality of life changed independently of either ( p<0.001 ) . Among controls , quality of life worsened ( p<0.001 ) whereas knowledge and behaviours remained unchanged . HDL cholesterol increased among patients on group care ( p=0.027 ) and total cholesterol decreased in the controls ( p<0.05 ) . HbA1c decreased , though not significantly , in both . Direct costs for group and one-to-one care were Euros 933.19 and Euros 697.10 per patient , respectively , giving a cost-effectiveness ratio of Euros 19.42 spent per point gained in the quality of life scale . CONCLUSIONS Group care is applicable and also cost-effective in type 1 diabetes . It improves quality of life , knowledge and behaviours . Future programme adjustments should strive to impact more on metabolic control Background . Hypertension is becoming a main health problem worldwide , but there is little evidence as to how care for hypertensive patients should be organized and delivered in the community to help improve blood pressure control . Group visit ( GV ) as a new care-delivering model has been shown to be less costly and have quality that is equal to or of better quality than usual care . The present study was conducted to evaluate the effectiveness of GVs for Chinese hypertensive patients compared with usual care . Methods . A r and omized , controlled trial was conducted , and a total of 1024 patients participated in the study . The patients in the GV groups received health care services in group format . The outcomes on blood pressure , treatment compliance , and self-efficacy were measured at baseline and at 6 months follow-up . Results . The average diastolic blood pressure decrease in the GV groups ( 1.5 mm Hg ) was more than that in the control groups ( 0.4 mm Hg ) significantly . In the GV groups , compliance with medicine , physical activities , and diet increased to 14.7 % , 9.7 % , and 10.1 % , respectively , which is more significant than that in the control groups ( 2.0 % , 1.6 % , and 8.0 % ) ; self-reported health and self-efficacy also improved significantly . Conclusion . The results suggest that the GV model is an acceptable and effective model for managing Chinese hypertensive patients in primary health care centers , and it could be a complement to the traditional individual office visit OBJECTIVE The aim of this study was to compare women 's satisfaction with group based antenatal care and st and ard care . DESIGN A r and omised control trial where midwives were r and omized to perform either GBAC or st and ard care . Women were invited to evaluate the two models of care . Data was collected by two question naires , in early pregnancy and six months after birth . Crude and adjusted odds ratios with a 95 % confidence interval were calculated by model of care . SETTING S Twelve antenatal clinics in Sweden between September 2008 and December 2010 . PARTICIPANTS Women in various part of Sweden ( n=700 ) . FINDINGS In total , 8:16 variables in GBAC versus 9:16 in st and ard care were reported as deficient . Women in GBAC reported significantly less deficiencies with information about labour/birth OR 0.16 ( 0.10 - 0.27 ) , breastfeeding OR 0.58 ( 0.37 - 0.90 ) and time following birth OR 0.61 ( 0.40 - 0.94 ) . Engagement from the midwives OR 0.44 ( 0.25 - 0.78 ) and being taken seriously OR 0.55 ( 0.31 - 0.98 ) were also found to be less deficient . Women in GBAC reported the highest level of deficiency with information about pregnancy OR 3.45 ( 2.03 - 5.85 ) but reported less deficiency with time to plan the birth OR 0.61 ( 0.39 - 0.96 ) . In addition , women in GBAC more satisfied with care in supporting contact with other parents OR 3.86 ( 2.30 - 6.46 ) and felt more support to initiate breastfeeding OR 1.75 ( 1.02 - 2.88 ) . CONCLUSIONS Women in both models of care considered the care as deficient in more than half of all areas . Variables that differed between the two models favoured group based antenatal care A 3-year r and omized clinical trial was conducted to test for differences in perinatal health behaviors , perinatal and infant health outcomes , and family health outcomes for women receiving group prenatal care ( GPC ) when compared to those receiving individual prenatal care . Women in GPC were almost 6 times more likely to receive adequate prenatal care than women in individual prenatal care and significantly more satisfied with their care . No differences were found by group for missed days of work , perceived stress , or social support . No differences in prenatal or postnatal depression symptoms were found in either group ; however , women in GPC were significantly less likely to report feelings of guilt or shame . The findings suggest that women in GPC have more adequate care and no untoward effects were found with the model . Further study is important to evaluate long-term outcomes of GPC Abstract Aims /hypothesis . Metabolic control worsens progressively in Type II ( non-insulin-dependent ) diabetes mellitus despite intensified pharmacological treatment and lifestyle intervention , when these are implemented on a one-to-one basis . We compared traditional individual diabetes care with a model in which routine follow-up is managed by interactive group visits while individual consultations are reserved for emerging medical problems and yearly checks for complications . Methods . A r and omized controlled clinical trial of 56 patients with non-insulin-treated Type II diabetes managed by systemic group education and 56 control patients managed by individual consultations and education . Results . Observation times were 51.2±2.1 months for group care and 51.2±1.8 for control subjects . Glycated haemoglobin increased in the control group but not in the group of patients ( p<0.001 ) , in whom BMI decreased ( p<0.001 ) and HDL-cholesterol increased ( p<0.001 ) . Quality of life , knowledge of diabetes and health behaviours improved with group care ( p<0.001 , all ) and worsened among the control patients ( p=0.004 to p<0.001 ) . Dosage of hypoglycaemic agents decreased ( p<0.001 ) and retinopathy progressed less ( p<0.009 ) among the group care patients than the control subjects . Diastolic blood pressure ( p<0.001 ) and relative cardiovascular risk ( p<0.05 ) decreased from baseline in group patients and control patients alike . Over the study period , group care required 196 min and 756.54 US $ per patient , compared with 150 min and 665.77 US $ for the control patients , result ing in an additional 2.12 US $ spent per point gained in the quality of life score . Conclusion /interpretation . Group care by systemic education is feasible in an ordinary diabetes clinic and cost-effective in preventing the deterioration of metabolic control and quality of life in Type II diabetes without increasing pharmacological treatment The military has recognized that health and quality of life for service members are closely tied to the re sources for their families , including how they are cared for during pregnancy and childbirth . However , there has been little examination of women 's experience with different models of prenatal care ( PNC ) in military setting s. The purpose of this article is to describe the results of a qualitative study of women 's experiences with the CenteringPregnancy model of group PNC compared to individual PNC in two military health care setting s. This clinical trial enrolled 322 women who were r and omized into group or individual PNC at two military treatment facilities . Qualitative interviews were completed with 234 women during the postpartum period . Interpretative narrative and thematic analysis was used to identify three themes : 1 ) " I was n't alone"-the experience with group PNC ; 2 ) " I liked it but ... "- recommendations to improve group PNC ; and 3 ) " They really need to listen"-general concerns across the sample about PNC . Greatest concerns of women in individual PNC included lack of continuity and time with the provider . Our military families must be assured that their health care system meets their needs through personal and family-centered care . Group PNC offers the potential for continuity of provider while also offering community with other women . In the process , women gain knowledge and power as a health care consumer BACKGROUND Diabetes mellitus ( DM ) group clinics can effectively control hypertension , but data to support glycemic control are equivocal . This study evaluated the comparative effectiveness of 2 DM group clinic interventions on glycosylated hemoglobin ( HbA(1c ) ) levels in primary care . METHODS Eighty-seven participants were recruited from a DM registry of a single regional Veterans Affairs medical center to participate in an open , r and omized comparative effectiveness study . Two primary care-based DM group interventions of 3 months ' duration were compared . Empowering Patients in Care ( EPIC ) was a clinician-led , patient-centered group clinic consisting of 4 sessions on setting self-management action plans ( diet , exercise , home monitoring , medications , etc ) and communicating about progress with action plans . The comparison intervention consisted of group education sessions with a DM educator and dietician followed by an additional visit with one 's primary care provider . Hemoglobin A(1c ) levels were compared after intervention and at the 1-year follow-up . RESULTS Participants in the EPIC intervention had significantly greater improvements in HbA(1c ) levels immediately following the active intervention ( 8.86%-8.04 % vs 8.74%-8.70 % of total hemoglobin ; mean [ SD ] between-group difference 0.67 % [ 1.3 % ] ; P=.03 ) , and these differences persisted at the 1 year follow-up ( 0.59 % [ 1.4 % ] , P=.05 ) . A repeated- measures analysis using all study time points found a significant time-by-treatment interaction effect on HbA(1c ) levels favoring the EPIC intervention ( F(2,85)=3.55 ; P=.03 ) . The effect of the time-by-treatment interaction seems to be partially mediated by DM self-efficacy ( F(1,85)=10.39 ; P=.002 ) . CONCLUSION Primary care-based DM group clinics that include structured goal - setting approaches to self-management can significantly improve HbA(1c ) levels after intervention and maintain improvements for 1 year . Trial Registration clinical trials.gov Identifier : NCT00481286 OBJECTIVE To compare the impact of group outpatient visits to traditional " physician-patient dyad " care among older chronically ill HMO members on health services utilization and cost , self-reported health status , and patient and physician satisfaction . DESIGN A 1-year r and omized trial . SETTING A group model HMO in the Denver Metropolitan area . PARTICIPANTS Three hundred twenty-one members aged 65 and older , r and omized to a group visit intervention ( n = 160 ) or to usual care ( n = 161 ) . INTERVENTION Patients with high health services utilization and one or more chronic conditions had monthly group visits with their primary care physician and nurse . Visits included health education , prevention measures , opportunities for socialization , mutual support , and for one-to-one consultations with their physician , where necessary . MEASUREMENTS Health services utilization and associated cost , health status , and patient and physician satisfaction . RESULTS Outcome measures obtained after a 1-year follow-up period showed that group participants had fewer emergency room visits ( P = .009 ) , visits to subspecialists ( P = .028 ) , and repeat hospital admissions per patient ( P = .051 ) . Group participants made more visits ( P = .021 ) and calls ( P = .038 ) to nurses than control group patients and fewer calls to physicians ( P = .019 ) . In addition , a greater percentage of group participants received influenza and pneumonia vaccinations ( P < .001 ) . Group participants had greater overall satisfaction with care ( P = .019 ) , and participating physicians reported higher levels of satisfaction with the groups than with individual care . No differences were observed between groups on self-reported health and functional status . Cost of care per member per month was $ 14.79 less for the group participants . CONCLUSIONS Group visits for chronically ill patients reduce repeat hospital admissions and emergency care use , reduce cost of care , deliver certain preventive services more effectively , and increase patient and physician satisfaction OBJECTIVE A trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics . RESEARCH DESIGN AND METHODS This study was a 4-year , two-armed , multicenter controlled trial in 13 hospital-based diabetes clinics in Italy ( current controlled trials no. IS RCT N19509463 ) . A total of 815 non – insulin-treated patients aged < 80 years with ≥1 year known diabetes duration were r and omized to either group or individual care . RESULTS After 4 years , patients in group care had lower A1C , total cholesterol , LDL cholesterol , triglycerides , systolic and diastolic blood pressure , BMI , and serum creatinine and higher HDL cholesterol ( P < 0.001 , for all ) than control subjects receiving individual care , despite similar pharmacological prescriptions . Health behaviors , quality of life , and knowledge of diabetes had become better in group care patients than in control subjects ( P < 0.001 , for all ) . CONCLUSIONS The favorable clinical , cognitive , and psychological outcomes of group care can be reproduced in different clinical setting |
11,121 | 32,420,161 | Conclusions bpMRI with high b-value is a sensitive tool for diagnosing PCa . | Background The purpose of this study is to systematic ally review the literature s assessing the value of dynamic contrast enhancement ( DCE ) in the multiparametric magnetic resonance imaging ( mpMRI ) for the diagnosis of prostate cancer ( PCa ) . | Purpose To vali date the dominant pulse sequence paradigm and limited role of dynamic contrast material -enhanced magnetic resonance ( MR ) imaging in the Prostate Imaging Reporting and Data System ( PI-RADS ) version 2 for prostate multiparametric MR imaging by using data from a multireader study . Material s and Methods This HIPAA-compliant retrospective interpretation of prospect ively acquired data was approved by the local ethics committee . Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging . A total of 163 patients were evaluated , 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings . Nine radiologists participated in this study and interpreted images in 58 patients , on average ( range , 56 - 60 patients ) . Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings . Probability of cancer detection for overall , T2-weighted , and diffusion-weighted ( DW ) imaging PI-RADS scores was calculated in the peripheral zone ( PZ ) and transition zone ( TZ ) by using generalized estimating equations . To determine dominant pulse sequence and benefit of dynamic contrast-enhanced ( DCE ) imaging , odds ratios ( ORs ) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression . Results A total of 654 lesions ( 420 in the PZ ) were detected . The probability of cancer detection for PI-RADS category 2 , 3 , 4 , and 5 lesions was 15.7 % , 33.1 % , 70.5 % , and 90.7 % , respectively . DW imaging outperformed T2-weighted imaging in the PZ ( OR , 3.49 vs 2.45 ; P = .008 ) . T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ ( OR , 4.79 vs 3.77 ; P = .494 ) . Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions ( 67.8 % vs 40.0 % , P = .02 ) . The addition of DCE imaging to DW imaging in the PZ was beneficial ( OR , 2.0 ; P = .027 ) , with an increase in the probability of cancer detection of 15.7 % , 16.0 % , and 9.2 % for PI-RADS category 2 , 3 , and 4 lesions , respectively . Conclusion DW imaging outperforms T2-weighted imaging in the PZ ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria . The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection . © RSNA , 2017 An earlier incorrect version of this article appeared online . This article was corrected on July 27 , 2017 . Online supplemental material is available for this article Purpose To compare the diagnostic performance of a short dual-pulse sequence magnetic resonance ( MR ) imaging protocol versus a st and ard six-pulse sequence multiparametric MR imaging protocol for detection of clinical ly significant prostate cancer . Material s and Methods This HIPAA-compliant study was approved by the regional ethics committee . Between July 2013 and March 2015 , 63 patients from a prospect ively accrued study population who underwent MR imaging of the prostate including transverse T1-weighted ; transverse , coronal , and sagittal T2-weighted ; diffusion-weighted ; and dynamic contrast material -enhanced MR imaging with a 3-T imager at a single institution were included in this retrospective study . The short MR imaging protocol image set consisted of transverse T2-weighted and diffusion-weighted images only . The st and ard MR imaging protocol image set contained images from all six pulse sequences . Three expert readers from different institutions assessed the likelihood of prostate cancer on a five-point scale . Diagnostic performance on a quadrant basis was assessed by using areas under the receiver operating characteristic curves , and differences were evaluated by using 83.8 % confidence intervals . Intra- and interreader agreement was assessed by using the intraclass correlation coefficient . Transperineal template saturation biopsy served as the st and ard of reference . Results At histopathologic evaluation , 84 of 252 ( 33 % ) quadrants were positive for cancer in 38 of 63 ( 60 % ) men . There was no significant difference in detection of tumors larger than or equal to 0.5 mL for any of the readers of the short MR imaging protocol , with areas under the curve in the range of 0.74 - 0.81 ( 83.8 % confidence interval [ CI ] : 0.64 , 0.89 ) , and for readers of the st and ard MR imaging protocol , areas under the curve were 0.71 - 0.77 ( 83.8 % CI : 0.62 , 0.86 ) . Ranges for sensitivity were 0.76 - 0.95 ( 95 % CI : 0.53 , 0.99 ) and 0.76 - 0.86 ( 95 % CI : 0.53 , 0.97 ) and those for specificity were 0.84 - 0.90 ( 95 % CI : 0.79 , 0.94 ) and 0.82 - 0.90 ( 95 % CI : 0.77 , 0.94 ) for the short and st and ard MR protocol s , respectively . Ranges for interreader agreement were 0.48 - 0.60 ( 83.8 % CI : 0.41 , 0.66 ) and 0.49 - 0.63 ( 83.8 % CI : 0.42 , 0.68 ) for the short and st and ard MR imaging protocol s. Conclusion For the detection of clinical ly significant prostate cancer , no difference was found in the diagnostic performance of the short MR imaging protocol consisting of only transverse T2-weighted and diffusion-weighted imaging pulse sequences compared with that of a st and ard multiparametric MR imaging protocol . © RSNA , 2017 Online supplemental material is available for this article Purpose To determine the diagnostic accuracy for clinical ly significant prostate cancer achieved with abbreviated biparametric prostate magnetic resonance ( MR ) imaging in comparison with full multiparametric contrast material -enhanced prostate MR imaging in men with elevated prostate-specific antigen ( PSA ) and negative transrectal ultrasonography (US)-guided biopsy findings ; to determine the significant cancer detection rate of biparametric versus full multiparametric contrast-enhanced MR imaging and between-reader agreement for interpretation of biparametric MR imaging . Material s and Methods In this institutional review board-approved retrospective review of prospect ively acquired data , men with PSA greater than or equal to 3 ng/mL after negative transrectal US-guided biopsy findings underwent state-of-the-art , full multiparametric contrast-enhanced MR imaging at 3.0-T including high-spatial-resolution structural imaging in several planes , diffusion-weighted imaging at 0 , 800 , 1000 , and 1400 mm2/sec , and dynamic contrast-enhanced MR imaging , obtained without endorectal coil within 34 minutes 19 seconds . One of four radiologists with different levels of expertise ( 1 - 9 years ) first review ed only a fraction of the full multiparametric contrast-enhanced MR images , consisting of single-plane ( axial ) structural imaging ( T2-weighted turbo spin-echo and diffusion-weighted imaging ) , acquired within 8 minutes 45 seconds ( referred to as biparametric MR imaging ) , and established a diagnosis according to the Prostate Imaging Reporting and Data System ( PI-RADS ) version 2 ; only thereafter , the remaining full multiparametric contrast-enhanced MR images were read . Men with PI-RADS categories 3 - 5 underwent MR-guided targeted biopsy . Men with PI-RADS categories 1 - 2 remained in urologic follow-up for at least 2 years , with rebiopsy ( transrectal US-guided or transperineal saturation ) where appropriate . McNemar test was used to compare diagnostic accuracies . To investigate between-reader agreement , biparametric MR images of 100 patients were read independently by all three radiologists . Results A total of 542 men , aged 64.8 years ± 8.2 ( median PSA , 7 ng/mL ) , were included . Biparametric MR imaging helped detect clinical ly significant prostate cancer in 138 men . Full multiparametric contrast-enhanced MR imaging allowed detection of one additional clinical ly significant prostate cancer ( a stage pT2a , intermediate-risk cancer with a Gleason score of 3 + 4 ) and caused 11 additional false-positive diagnoses . Diagnostic accuracy for detection of clinical ly significant cancer of biparametric MR imaging ( 89.1 % , 483 of 542 ) was similar to that of full multiparametric contrast-enhanced MR imaging ( 87.2 % , 473 of 542 ) . Between-reader agreement of biparametric MR imaging interpretation was substantial ( κ = 0.81 ) . Conclusion Biparametric MR imaging allows detection of clinical ly significant prostate cancer missed by transrectal US-guided biopsy . Biparametric prostate MR imaging takes less than 9 minutes examination time , works without contrast agent injection , and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MR imaging protocol s. © RSNA , 2017 PURPOSE To prospect ively evaluate multiparametric magnetic resonance imaging ( MRI ) for accurate localization of intraprostatic tumor nodules , with whole-mount histopathology as the gold st and ard . MATERIAL S AND METHODS Seventy-five patients with biopsy-proven , intermediate , and high-risk prostate cancer underwent preoperative T2-weighted ( T2w ) , dynamic contrast-enhanced ( DCE ) and diffusion-weighted ( DW ) MRI at 1.5 T . Localization of suspicious lesions was recorded for each of 24 st and ardized regions of interest on the different MR images and correlated with the pathologic findings . Generalized estimating equations ( GEE ) were used to estimate the sensitivity , specificity , accuracy , positive , and negative predictive value for every MRI modality , as well as to evaluate the influence of Gleason score and pT-stage . Tumor volume measurements on histopathological specimens were correlated with those on the different MR modalities ( Pearson correlation ) . RESULTS DW MRI had the highest sensitivity for tumor localization ( 31.1 % vs. 27.4 % vs. 44.5 % for T2w , DCE , and DW MRI , respectively ; P < 0.005 ) , with more aggressive or more advanced tumors being more easily detected with this imaging modality . Significantly higher sensitivity values were obtained for the combination of T2w , DCE , and DW MRI ( 58.8 % ) as compared to each modality alone or any combination of two modalities ( P < 0.0001 ) . Tumor volume can most accurately be assessed by means of DW MRI ( r = 0.75 ; P < 0.0001 ) . CONCLUSION Combining T2w , DCE , and DW imaging significantly improves prostate cancer localization Abstract Objectives To measure the performance characteristics of combined T2-weighted ( T2W ) and diffusion-weighted ( DW ) magnetic resonance imaging ( MRI ) suspicion scoring prior to MR-transrectal ultrasound ( TRUS ) fusion template transperineal ( TTP ) re-biopsy . Methods Thirty-nine patients referred for prostate re-biopsy , with prior MRI examinations , were retrospectively included . The MR images , including T2W and DW-MRI , had been independently evaluated prospect ively by two radiologists using a structured scoring system . An MR-TRUS fusion TTP re-biopsy was used for MR target and non-targeted biopsy cores . Targeting performance and correlation with disease status were evaluated on a per-patient and per-region basis . Results The cancer yield was 41 % ( 16/39 patients ) . MR targeting accurately detected the disease in 12/16 ( 75 % ) cancerous patients and missed the disease in 4/16 ( 25 % ) patients , all with Gleason 3 + 3 disease . There was a significant relationship ( P < 0.01 ) between MR suspicion score and the significance of cancer . Reader 1 had significantly higher sensitivity in the transition zone ( TZ ; 0.84 ) compared with the peripheral zone ( PZ ; 0.32 ) ( P = 0.04 ) . Inter-reader agreement was moderate for the PZ and substantial for the TZ . Conclusions MRI targeting is beneficial in the setting of TTP MR-TRUS fusion re-biopsy and MR suspicion score relates to prostate cancer clinical significance . A T2W and DW-MRI structured scoring system results in good inter-reader agreement in this setting .Key Points• Pre-biopsy MRI aids the detection of high significance cancer during prostate re-biopsy . • MRI suspicion level correlates with the clinical significance of prostate cancer detected . • T2W and DW-MRI structured scoring of pre-biopsy MRI permits good inter-reader agreement PURPOSE To determine whether the fusion of multiparametric magnetic resonance imaging ( MRI ) with transrectal real-time elastography ( RTE ) improves the visualization of PCa lesions compared to MRI alone . MATERIAL S AND METHODS In a prospect i ve setting , 45 patients with biopsy-proven PCa received prostate MRI prior to radical prostatectomy ( RP ) . T2 and diffusion-weighted imaging ( T2WI/DW-MRI ) and , if applicable , dynamic contrast-enhanced sequences ( T2WI/DW/DCE-MRI ) were used to perform MRI/RTE fusion . The probability of PCa on MRI was grade d according to the PI-RADS score for 12 different prostate sectors per patient . MRI images were fused with RTE to stratify suspicious from non-suspicious sectors . Imaging results were compared to whole mount sections using nonparametrical receiver operating characteristic curves and the area under these curves ( AUC ) . RESULTS 41 of 45 patients were eligible for final analyses . Histopathology confirmed PCa in 261 ( 53 % ) of 492 prostate sectors . MRI alone provided an AUC of 0.62 ( T2WI/DW-MRI ) and 0.65 ( T2WI/DW/DCE-MRI ) to predict PCa and was meaningfully enhanced to 0.75 ( T2WI/DW-MRI ) and 0.74 ( T2WI/DW/DCE-MRI ) using MRI/RTE fusion . Sole MRI showed a sensitivity and specificity of 57.9 % and 61 % with the best results for ventral prostate sectors whereas RTE was superior in dorsal and apical sectors . MRI/RTE fusion improved sensitivity and specificity to 65.9 % and 75.3 % , respectively . Additional use of DCE sequences showed a sensitivity and specificity of 65 % and 55.7 % for MRI and 72.1 % and 66 % for MRI/RTE fusion . CONCLUSION MRI/RTE fusion provides improved PCa visualization by combining the strength of both imaging techniques in regard to prostate zonal anatomy and thereby might improve future biopsy-guided PCa detection Background Since multiparametric magnetic resonance imaging ( mp-MRI ) of the prostate exceeds 30 min , minimizing the evaluation time of significant ( Gleason scores > 6 ) prostate cancer ( PCa ) would be beneficial . A reduced protocol might be sufficient for the diagnosis . Purpose To study whether a short unenhanced biparametric MRI ( bp-MRI ) matches mp-MRI in detecting significant PCa . Material and Methods A total of 204 men ( median age , 65 years ; mean ± SD , 64.1 ; range 45–75 years ; median serum PSA level , 14 ng/mL ; range , 2.2–120 ng/mL ; median prostate volume , 60 mL ; range , 23–263 mL ) fulfilled the criteria for being enrolled . They underwent mp-MRI and prostate biopsy from January through June 2014 . Of the included patients , 9.3 % underwent prostatectomy , 90.7 % had TRUS-bx , and 10.8 had MRI-targeted TRUS-bx . Two radiologists separately assessed the mp-MRI examination ( T2-weighted [ T2W ] imaging , diffusion-weighted imaging [ DWI ] , apparent diffusion coefficient map [ ADC-map ] and dynamic contrast-enhanced imaging [ DCE ] ) . Two months later , the bp-MRI version ( T2W imaging , DWI , and ADC-map ) was evaluated . Results Reader 1 : Assessing mp-MRI : 0 false negatives , sensitivity of 1 , and specificity 0.04 . Assessing bp-MRI : four false negatives , sensitivity of 0.94 , and specificity 0.15 . Reader 2 : Assessing mp-MRI : five false negatives , sensitivity of 0.93 , and specificity 0.16 . Assessing bp-MRI : three false negatives , sensitivity of 0.96 , and specificity 0.15 . Intra-reader agreement Cohen ’s Kappa ( κ ) was 0.87 for reader 1 ( 95 % confidence interval [ CI ] , 0.83–0.92 ) and 0.84 for reader 2 ( 95 % CI 0.78–0.89 ) . Conclusion Bp-MRI is as good as mp-MRI at detecting PCa . A large prospect i ve study seems to be strongly warranted To study the staging accuracy of multiparametric magnetic resonance imaging ( MRI ) in patients showing unilateral low-risk cancer on prostate biopsy . A total of 58 consecutive patients with low-risk cancer ( D'Amico classification ) and unilateral cancer involvement on prostate biopsies were included prospect ively . All patients underwent multiparametric endorectal MRI before radical prostatectomy , including T2-weighted ( T2W ) , diffusion-weighted ( DW ) and dynamic contrast enhanced ( DCE ) sequences . Each gl and was divided in eight octants . Tumor foci > 0.2 cm3 identified on pathological analysis were matched with MRI findings . Pathological examination showed tumor foci > 0.2 cm3 in 50/58 gl and s ( 86 % ) , and bilateral tumor ( pathological stage⩾pT2c ) in 20/58 ( 34 % ) . For tumor detection in the peripheral zone ( PZ ) , T2W+DWI+DCE performed significantly better than T2W+DWI and T2W alone ( P<0.001 ) . In the transition zone ( TZ ) , only T2W+DWI performed better than T2W alone ( P=0.02 ) . With optimal MR combinations , tumor size was correctly estimated in 77 % of tumor foci involving more than one octant . Bilateral tumors were detected in 80 % ( 16/20 ) of cases . In patients with unilateral low-risk prostate cancer on biopsy , multiparametric MRI can help to predict bilateral involvement . Multiparametric MRI may therefore have a prognostic value and help to determine optimal treatment in such patients OBJECTIVES To prospect ively determine the diagnostic accuracy of a biparametric 3 T magnetic resonance imaging protocol ( BP-MRI ) for prostatic cancer detection , compared to a multiparametric MRI protocol ( MP-MRI ) , in a biopsy naïve patient population . METHODS Eighty-two untreated patients ( mean age 65±7.6years ) with clinical suspicion of prostate cancer and /or altered prostate-specific antigen ( PSA ) levels underwent a MP-MRI , including T2-weighted imaging , diffusion-weighted imaging ( with the correspondent apparent diffusion coefficient maps ) and dynamic contrast enhanced sequence , followed by prostate biopsy . Two radiologists review ed both the BP-MRI and the MP-MRI protocol s to establish a radiological diagnosis . Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocol s. RESULTS The mean PSA level was 8.8±8.1ng/ml . A total of 34 prostatic tumors were identified , with a Gleason score that ranged from 3 + 3 to 5 + 4 . Of these 34 tumors , 29 were located within the peripheral zone and 5 in the transitional zone . BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy , with an area under the curve of 0.91 and 0.93 , respectively ( p = n.s . ) . CONCLUSIONS BP-MRI prostate protocol is feasible for prostatic cancer detection compared to a st and ard MP-MRI protocol , requiring a shorter acquisition and interpretation time , with comparable diagnostic accuracy to the conventional protocol , without the administration of gadolinium-based contrast agent OBJECTIVE Immediate and early loading of implants can simplify treatment and increase patient satisfaction . This 3-year r and omized-controlled trial will therefore evaluate survival rates and bone-level changes with immediately and early loaded Straumann implants with the SLActive surface . MATERIAL AND METHODS Partially edentulous patients > or=18 years of age were enrolled . Patients received a temporary restoration ( single crown or two to four unit fixed partial denture ) out of occlusal contact either immediately ( immediate loading ) or 28 - 34 days later ( early loading group ) , with permanent restorations placed 20 - 23 weeks after surgery . The primary endpoint was change in crestal bone level from baseline ( implant placement ) to 12 months ; the secondary variables were implant survival and success rates . RESULTS A total of 383 implants ( 197 immediate and 186 early ) were placed in 266 patients ; 41.8 % were placed in type III and IV bone . The mean patient age was 46.3+/-12.8 years . Four implants failed in the immediate loading group and six in the early loading group , giving implant survival rates of 98 % and 97 % , respectively ( P = NS ) . There were no implant failures in type IV bone . The overall mean bone level change from baseline to 12 months was 0.77+/-0.93 mm ( 0.90+/-0.90 and 0.63+/-0.95 mm in the immediate and early groups , respectively ; P<0.001 ) . However , a significant difference in implantation depth between the two groups ( P<0.0001 ) was found . After adjusting for this slight difference in initial surgical placement depth , time to loading no longer had a significant influence on bone-level change . Significant influence was found for : center ( P<0.0001 ) , implant length ( P<0.05 ) and implant position ( P<0.0001 ) . Bone gain was observed in approximately 16 % of implants . CONCLUSIONS The results demonstrated that Straumann implants with the SLActive surface are safe and predictable when used in immediate and early loading procedures . Even in poor- quality bone , survival rates were comparable with those from conventional or delayed loading . The mean bone-level change was not deemed to be clinical ly significant and compared well with the typical bone resorption observed in conventional implant loading Background : Conventional T2-weighted ( T2W ) imaging alone has a poor sensitivity for prostate cancer detection . Purpose : To evaluate combined T2W and diffusion-weighted magnetic resonance imaging ( DW-MRI ) versus T2W MRI alone for identifying tumor in patients with prostate cancer . Material and Methods : Fifty-four consecutive patients with prostate cancer ( 46 stage 1 and 2 , 8 stage 3 ) and sextant biopsies within the previous 3 months were studied . Endorectal MR images were analyzed by two radiologists ( 1 experienced , 1 trainee ) blinded to patient information and histopathology . T2W images were scored first , followed by combined T2W and isotropic apparent diffusion coefficient ( ADC ) maps calculated from DW-MRI ( b = 0 , 300 , 500 , and 800 s/mm2 ) . Gl and apex , middle , and base for each side were scored negative , indeterminate , or positive for tumor . Imaging data for each sextant were compared with histology . Sensitivity , specificity , and interobserver agreement were calculated . Results : Sensitivity and specificity for tumor identification significantly improved from 50 % and 79.6 % ( T2W alone , experienced observer ) to 73.2 % and 80.8 % ( P<0.001 ) , respectively . For the trainee observer , there was no improvement ( 44.3 % and 72 % T2W alone vs. 45.1 % and 69.2 % T2W plus ADC maps ) . Interobserver agreement was moderate for T2W imaging alone ( kappa 0.51 ) and fair for T2W plus ADC maps ( kappa 0.33 ) . Conclusion : In an experienced observer , DW-MRI together with T2W imaging can significantly improve tumor identification in prostate cancer OBJECTIVE The objective of our study was to compare T2-weighted MRI alone and T2 combined with diffusion-weighted imaging ( DWI ) for the localization of prostate cancer . SUBJECTS AND METHODS T2-weighted imaging and DWI ( b value = 600 s/mm2 ) were performed in 49 patients before radical prostatectomy using an endorectal coil at 1.5 T in this prospect i ve trial . The peripheral zone of the prostate was divided into sextants and the transition zone into left and right halves . T2 images alone and then T2 images combined with apparent diffusion coefficient ( ADC ) maps ( T2 + DWI ) were scored for the likelihood of tumor and were compared with whole-mount histology results . Fixed window and level setting s were used to display the ADC maps . Only tumors with an area of more than 0.13 cm2 ( > 4 mm diameter ) and a Gleason score of > or = 6 were considered significant . The area under the receiver operating characteristic curve ( A(z ) ) was used to assess accuracy . RESULTS In the peripheral zone , the A(z ) value was significantly higher ( p = 0.004 ) for T2 plus DWI ( A(z ) = 0.89 ) than for T2 imaging alone ( A(z ) = 0.81 ) . Performance was poorer in the transition zone for both T2 plus DWI ( A(z ) = 0.78 ) and T2 ( A(z ) = 0.79 ) . For the whole prostate , sensitivity was significantly higher ( p < 0.001 ) with T2 plus DWI ( 81 % [ 120/149 ] ) than with T2 imaging alone ( 54 % [ 81/149 ] ) , with T2 plus DWI showing only a slight loss in specificity compared with T2 imaging alone ( 84 % [ 204/243 ] vs 91 % [ 222/243 ] , respectively ) . CONCLUSION Combined T2 and DWI MRI is better than T2 imaging alone in the detection of significant cancer ( Gleason score > or = 6 and diameter > 4 mm ) within the peripheral zone of the prostate BACKGROUND Multiparametric magnetic resonance imaging ( MRI ) combined with prostate-specific-antigen density ( PSAd ) enhances the detection of significant prostate cancer ( sPCa ) . However , it is unclear whether simple biparametric ( bp ) MRI , which reduces scan sequences , time , and cost , may be an equally effective noninvasive tool for detecting and ruling out sPCa and avoiding biopsies in biopsy-naïve men . OBJECTIVE To assess the diagnostic accuracy , predictive values , and best biopsy strategy combining bpMRI and PSAd in detecting and ruling out sPCa ( Gleason score ≥7 ) . DESIGN , SETTING , AND PARTICIPANTS Assessment of 808 biopsy-naïve men with clinical suspicion of localised PCa ( prostate-specific antigen < 20ng/ml , rectal examination < cT3 ) , prospect ively enrolled between November 2015 and June 2017 . INTERVENTION All men underwent upfront bpMRI ( T2- and diffusion-weighted imaging ) followed by st and ard and targeted biopsies of any suspicious bpMRI findings . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Various bpMRI scores and PSAd thresholds were assessed using sPCa detection rates , predictive values , and proportion of biopsies avoided . Net benefits and decision curve analyses were compared . Combined biopsies from all men were used for reference . RESULTS AND LIMITATIONS Significant prostate cancers were detected in 283/808 ( 35 % ) men with median age and PSA ( interquartile range ) of 65 yr ( 60 - 70 ) and 6.9ng/ml ( 5.4 - 9.5 ) , respectively . PSAd significantly influenced the predictive values of bpMRI in detecting and ruling out sPCa . The best strategy was restricting biopsies to men with highly suspicious bpMRI findings ( score ≥4 ) or PSAd ≥0.15ng/ml/cc . This reduced the number of men requiring biopsies by 41 % ( 329/808 ) and overdiagnosis of insignificant cancers by 45 % ( 79/177 ) , while missing only 5 % ( 17/329 ) of men with sPCa . Study limitations included single-centre analysis and combined biopsies as the reference st and ard . CONCLUSIONS Combination of bpMRI with PSAd improves diagnostic accuracy and predictive values for sPCa detection in biopsy-naïve men . Restricting biopsies to men with highly suspicious bpMRI findings ( score ≥4 ) or PSAd ≥0.15ng/ml/cc was the best biopsy strategy in our patient cohort , effectively balancing risks and benefits . Studies are needed to vali date our findings in other patient population s. PATIENT SUMMARY This report shows that biopsy-naïve men with clinical suspicion of prostate cancer who have low- or equivocal-suspicion biparametric magnetic resonance imaging results and a low prostate-specific antigen density may not require immediate prostate biopsies BACKGROUND Biparametric magnetic resonance imaging ( bpMRI ) combined with prostate-specific antigen density ( PSAd ) may be an effective strategy for selecting men for prostate biopsy . It has been shown that performing biopsy only for men with bpMRI Likert scores of 4 - 5 or PSAd ≥0.15 ng/ml/cm3 is the most efficient strategy . OBJECTIVE To externally vali date previously published biopsy strategies using two prospect i ve bpMRI trial cohorts . DESIGN , SETTING , AND PARTICIPANTS After IMPROD bpMRI , 499 men had systematic transrectal prostate biopsies and men with IMPROD bpMRI Likert scores of 3 - 5 had an additional two to four targeted biopsies . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Various IMPROD bpMRI Likert score and PSAd thresholds were assessed using detection rates for significant prostate cancer ( sPCa ; Gleason score ≥3 + 4 ) , predictive values , and proportion of biopsies avoided . Net benefits and decision curve analyses ( DCA ) were compared with the aim of finding an optimal strategy for sPCa detection . Combined biopsies were used for reference . RESULTS AND LIMITATIONS The negative predictive value ( NPV ) for sPCa in IMPROD bpMRI Likert 3 - 5 and 4 - 5 score groups was 93 % and 92 % , respectively , while the corresponding positive predictive value ( PPV ) was 57 % and 72 % , respectively . In DCA , the optimal combination was IMPROD bpMRI Likert score 4 - 5 or Likert 3 with PSAd ≥0.20 ng/ml/cm3 , which had NPV of 93 % and PPV of 67 % . Using this combination , 35 % of the study patients would have avoided biopsies and 13 sPCas ( 6 % , 13/229 , of all sPCas diagnosed ) would have been missed . CONCLUSIONS IMPROD bpMRI demonstrated a good NPV for sPCa . PSAd improved the NPV mainly among men with equivocal suspicion on IMPROD bpMRI . However , the additional value of PSAd was marginal : the NPV and PPV for IMPROD bpMRI Likert 4 - 5 score group were 92 % and 72 % , respectively , while the corresponding values for the best combination strategy were 93 % and 67 % . PATIENT SUMMARY We investigated a rapid prostate magnetic resonance imaging protocol ( IMPROD bpMRI ) combined with prostate-specific antigen ( PSA ) density for detection of significant prostate cancer . Our results show that IMPROD bpMRI is a good diagnostic tool , but the additional value provided by PSA density is marginal |
11,122 | 26,883,751 | Conclusions Although the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection , the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy .
Besides , the combined modality did not help lower the false-negative rate | Background The combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes ( SLNs ) in patients with breast cancer .
However , some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs .
We performed a systematic review to investigate the added value of blue dye in addition to radioisotope . | Background We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node ( SLN ) mapping at a high-volume institution . Methods Using a prospect ively maintained data base , 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified . Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review . Statistical analysis was performed with Student t test and chi-square analysis . Results 2,049 ( 60.2 % ) patients underwent mapping with dual technique , and 1,353 ( 39.8 % ) with radioisotope only . Blue dye use decreased gradually over time ( 69.8 % in 2002 to 48.3 % in 2006 , p < 0.0001 ) . Blue dye was used significantly more frequently in patients with lower axillary counts , higher body mass index ( BMI ) , African-American race , and higher T stage , and in patients not undergoing skin-sparing mastectomy . There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone ( both 98.4 % ) . Four ( 0.8 % ) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN . None of these four had significant counts detected in the axilla intraoperatively . Nine ( 0.4 % ) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye . Conclusions Blue dye use has decreased with increasing institutional experience with SLN mapping . In patients with adequate radioactive counts in the axilla , blue dye is unlikely to improve the success of sentinel node mapping PURPOSE To determine the detection rate , the false-negative rate , and the accuracy of sentinel lymph node ( SLN ) detection after neoadjuvant chemotherapy ( NAC ) for advanced breast cancer . PATIENTS AND METHODS A prospect i ve multicentric study was initiated to evaluate the results of SLN biopsy with the combined method after NAC for advanced large operable breast cancer . RESULTS From September 2003 to March 2007 , 195 patients enrolled from 12 institutions were found suitable for evaluation . The detection rate was 90 % ( 176 of 195 patients ) , and the false-negative rate was 11.5 % ( six of 52 patients ) . Patients without axillary palpable nodes ( N0 ) before NAC had a better detection rate compared with patients with axillary suspicious nodes ( N1 , 94.6 % v 81.5 % ; P = .008 ) . The false-negative rate was not correlated with clinical nodal status before NAC ( 9.4 % v 15 % ; P = .66 ) . CONCLUSION This study confirms the feasibility of SLN biopsy after NAC in the case of large operable breast cancer . The detection rate , false-negative rate , and accuracy do not differ from those obtained in the case of early breast cancer without NAC , thus demonstrating the feasibility of SLN biopsy after NAC Background Sentinel lymph node ( SLN ) mapping with radioisotope and blue dye is rapidly becoming the st and ard of care for breast cancer . The optimal location for injection of radioisotope and blue dye is still being investigated . The goal of this study was to determine whether blue dye injection into the subareolar ( SA ) location localized the same sentinel nodes as the peritumoral ( PT ) location for patients with breast cancer . Methods Three hundred thirty-two patients with biopsy-proven operable breast cancer or ductal carcinoma in situ at two institutions underwent SLN mapping . Eighty-three patients had PT injection of blue dye ( group 1 ) , and 249 patients had SA injection of blue dye ( group 2 ) . All patients underwent PT injection of99mTc-labeled sulfur colloid . Results The two groups were similar in age , previous biopsy type , and tumor size , location , and histology . The mean number of SLNs identified was 2.4 ( range , 0–9 ) in group 1 and 2.5 ( range , 0–11 ) in group 2 . The SLN identification rate was 95 % for group 1 and 97 % for group 2 . The isotope success rate was 94 % for both groups . The blue dye success rate was 84 % for group 1 and 90 % for group 2 . The isotope/blue dye concordance rate was 87 % for group 1 and 90 % for group 2 . At a median follow-up of 28 months ( range , 14 to 40 ) , there were no axillary recurrences in any of the 332 patients . Conclusions These data suggest that delivery of mapping reagents in the SA and PT locations identifies similar lymph nodes . Because of simplicity and the similarity in node identification between SA and PT injection , further investigation of the SA site for delivery of SLN mapping reagents for breast cancer is warranted Purpose To provide current recommendations on the use of sentinel node biopsy ( SNB ) for patients with early-stage breast cancer . Methods PubMed and the Cochrane Library were search ed for r and omized controlled trials , systematic review s , meta-analyses , and clinical practice guidelines from 2012 through July 2016 . An Up date Panel review ed the identified abstract s. Results Of the eight publications identified and review ed , none prompted a change in the 2014 recommendations , which are reaffirmed by the up date d literature review . Conclusion Women without sentinel lymph node ( SLN ) metastases should not receive axillary lymph node dissection ( ALND ) . Women with one to two metastatic SLNs who are planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND ( in most cases ) . Women with SLN metastases who will undergo mastectomy should be offered ALND . These three recommendations are based on r and omized controlled trials . Women with operable breast cancer and multicentric tumors , with ductal carcinoma in situ , who will undergo mastectomy , who previously underwent breast and /or axillary surgery , or who received preoperative/neoadjuvant systemic therapy may be offered SNB . Women who have large or locally advanced invasive breast cancer ( tumor size T3/T4 ) , inflammatory breast cancer , or ductal carcinoma in situ ( when breast-conserving surgery is planned ) or are pregnant should not undergo SNB PURPOSE To develop a guideline for the use of sentinel node biopsy ( SNB ) in early stage breast cancer . METHODS An American Society of Clinical Oncology ( ASCO ) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer . The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB . The guideline was review ed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors . RESULTS The literature review identified one published prospect i ve r and omized controlled trial in which SNB was compared with axillary lymph node dissection ( ALND ) , four limited meta-analyses , and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND ( completion axillary dissection ) . There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer . However , a review of the available evidence demonstrates that , when performed by experienced clinicians , SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes . CONCLUSION SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinical ly negative axillary nodes . Completion ALND remains st and ard treatment for patients with axillary metastases identified on SNB . Appropriately identified patients with negative results of SNB , when done under the direction of an experienced surgeon , need not have completion ALND . Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance . Although such specialized techniques are often used , they are not a required part of SLN evaluation for breast cancer at this time . Data suggest that SNB is associated with less morbidity than ALND , but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown The combination of preoperative lymphatic mapping with intra-operative probe detection is becoming the st and ard procedure for identifying tumour lymphatic spread at the time of initial treatment in breast cancer . There are a number of identification techniques for sentinel lymph nodes , but the concordance of the results of a sentinel lymph node biopsy with axillary lymph node dissection did not vary significantly among them . Periareolar ( p.a . ) injection of tracer is a new procedure specifically studied to overcome some limitations of other techniques ; in two groups of patients with early breast cancer we compared the periareolar with the subdermal technique . One hundred and fifty biopsy proven breast cancer patients were consecutively enrolled in this study . This population was divided into two groups : ( 1 ) group A , including 100 cancers ; lymphatic mapping was performed by s.d . injection of both blue dye and radiotracer ; and ( 2 ) group B , including 50 cancers ; lymphatic mapping was performed with a combination of blue dye injected p.a . and radiotracer injected s.d . For group A , with both techniques we identified one or more SLNs in 100/100 tumours ; blue dye detected the SLNs in 99/100 cancers ( 99 % ) , lymphoscintigraphy in 93/100 cancers ( 93 % ) . The concordance rate was 92 % . For group B , with both techniques we identified one or more SLNs in 49/50 cancers ( 98 % ) ; blue dye detected the SLNs in 48/50 , lymphoscintigraphy in 46/50 cancers ( 92 % ) . The concordance rate was 92 % . In the present study p.a . and s.d . injection of blue dye give similar and comparable results . The periareolar technique is simpler and has several advantages over the subdermal technique BACKGROUND The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain . The SENTINA ( SENTinel NeoAdjuvant ) study was design ed to evaluate a specific algorithm for timing of a st and ardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy . METHODS SENTINA is a four-arm , prospect i ve , multicentre cohort study undertaken at 103 institutions in Germany and Austria . Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study . Patients with clinical ly node-negative disease ( cN0 ) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy ( arm A ) . If the sentinel node was positive ( pN1 ) , a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy ( arm B ) . Women with clinical ly node-positive disease ( cN+ ) received neoadjuvant chemotherapy . Those who converted to clinical ly node-negative disease after chemotherapy ( ycN0 ; arm C ) were treated with sentinel-lymph-node biopsy and axillary dissection . Only patients whose clinical nodal status remained positive ( ycN1 ) underwent axillary dissection without sentinel-lymph-node biopsy ( arm D ) . The primary endpoint was accuracy ( false-negative rate ) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy ( arm C ) . Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy , and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node . Analyses were done according to treatment received ( per protocol ) . FINDINGS Of 1737 patients who received treatment , 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy ( arms A and B ) , with a detection rate of 99.1 % ( 95 % CI 98.3 - 99.6 ; 1013 of 1022 ) . In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 ( arm C ) , the detection rate was 80.1 % ( 95 % CI 76.6 - 83.2 ; 474 of 592 ) and false-negative rate was 14.2 % ( 95 % CI 9.9 - 19.4 ; 32 of 226 ) . The false-negative rate was 24.3 % ( 17 of 70 ) for women who had one node removed and 18.5 % ( 10 of 54 ) for those who had two sentinel nodes removed ( arm C ) . In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy ( arm B ) , the detection rate was 60.8 % ( 95 % CI 55.6 - 65.9 ; 219 of 360 ) and the false-negative rate was 51.6 % ( 95 % CI 38.7 - 64.2 ; 33 of 64 ) . INTERPRETATION Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy . After systemic treatment or early sentinel-lymph-node biopsy , the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy . These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy . FUNDING Brustkrebs Deutschl and , German Society for Senology , German Breast Group Methods of sample size and power calculations are review ed for the most common study design s. The sample size and power equations for these design s are shown to be special cases of two generic formulae for sample size and power calculations . A computer program is available that can be used for studies with dichotomous , continuous , or survival response measures . The alternative hypotheses of interest may be specified either in terms of differing response rates , means , or survival times , or in terms of relative risks or odds ratios . Studies with dichotomous or continuous outcomes may involve either a matched or independent study design . The program can determine the sample size needed to detect a specified alternative hypothesis with the required power , the power with which a specific alternative hypothesis can be detected with a given sample size , or the specific alternative hypotheses that can be detected with a given power and sample size . The program can generate help messages on request that facilitate the use of this software . It writes a log file of all calculated estimates and can produce an output file for plotting power curves . It is written in FORTRAN-77 and is in the public domain The purpose of the present work was two-fold : 1 ) to evaluate the predictive value of the sentinel lymph node ( sLN ) versus the axillary-node status in patients with T1-T2 breast cancer , and 2 ) to form an experimental basis for a r and omized trial in which one group of patients with non-metastatic sLN will not have axillary dissection . Of a group of 284 patients considered for this analysis , 264 had a T1 cancer ( 16 T1a , 37 T1b and 211 T1c ) , while 20 had a T2 cancer ; 243 patients were in clinical stage N0 and 41 were N1 . All patients underwent lymphoscintigraphy 18 hr before surgery : 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids ( particle size between 50 - 80 nm ) was injected subdermally at the cutaneous projection of the tumor . Static gamma-camera images were acquired every 10 - 15 minutes until scintigraphic identification of the sLN . At surgery , 1 - 2 mL of Patent-Blue Violet was injected subdermally , and the sLN was search ed by gamma-probe and by the dye method . The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin ( H&E ) histology , then for delayed histological and immunohistochemical examinations . The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases ( 97.9 % ) . The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone ( 56.3 % versus 97.2 % ) . Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing st and ard axillary dissection irrespective of the sLN status . Overall , 63/191 ( 33 % ) identified sLNs were metastatic , the sLN alone being involved in 37/63 ( 58.7 % ) patients ; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement ( 13.7 % false-negative rate ) . In conclusion , subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping ; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN . There was a high , but not absolute , correlation between a negative sLN and a negative axilla Summary Background Despite the widespread application of sentinel lymph node biopsy ( SLNB ) for early stage breast cancer , there is a wide variation in reported test performance characteristics . A major aim of this prospect i ve multicentre validation study was to quantify detection and false-negative rates of SLNB and evaluate factors influencing them . Methods Eight-hundred and fourty-two patients with clinical ly node-negative breast cancer underwent SLNB according to a st and ardised protocol that used a combination of radiopharmaceutical 99mTc-albumin colloid and Patent Blue V dye . SLNB was followed by st and ard axillary treatment at the same operation in all patients . Results Sentinel lymph nodes ( SLNs ) were identified in 803 ( 96.1 % ) of 836 evaluable cases . The median number of SLNs removed per patient was 2 ( range 1–9 ) . There were 19 false negatives , result ing in a sensitivity of 263/282 ( 93.3 % ) and accuracy 782/803 ( 97.6 % ) . SLNs were successfully identified by blue dye in 698 ( 85.6 % ) , by isotope in 698 ( 85.6 % ) , and by the combination of blue dye and isotope in 782 ( 96.0 % ) of 815 patients . Among 276 node positive patients , one or more positive SLNs were identified by blue dye in 251 ( 90.9 % ) , by isotope in 246 ( 89.1 % ) and by the combination of blue dye and gamma probe in 258 ( 93.5 % ) . Obesity , tumor location other than upper outer quadrant and non-visualisation of SLNs on the pre-operative lymphoscintiscan were significantly associated with failed localisation ( p<0.001 , p=0.008 , p<0.001 , respectively ) . The false-negative rate in patients with grade 3 tumors was 9.6 % , compared with 4.7 % in those with grade 2 tumors ( p=0.022 ) . The false-negative rate in patients who had one SLN harvested was 10.1 % , compared with 1.1 % in those who had multiple SLNs ( three or more ) removed ( p=0.010 ) . ConclusionS LNB can accurately determine whether axillary metastases are present in patients with early stage breast cancer with clinical ly negative axillary nodes . Both success and accuracy of SLNB are optimised by the combined use of blue dye and isotope . SLNB success decreases with increasing body mass , tumor location other than the upper outer quadrant and non-visualisation of hot nodes on the pre-operative lymphoscintiscan . This study demonstrates reduction in the predictive value of a negative SLNB in grade 3 tumors We have recently reported on a technique of gamma probe localization of radiolabelled lymph nodes to identify the sentinel node in malignant melanoma . In order to determine whether this technique is applicable to assist in staging breast cancer , a pilot study was begun to address two questions : ( i ) can the sentinel lymph node draining a breast cancer be identified for selective resection ; and ( ii ) is the sentinel lymph node predictive of the status of the entire axillary lymph nodes ? One to four hours prior to axillary lymph node dissection , 22 consecutive patients had approximately 0.4 mCi of technetium sulfur colloid in 0.5 ml saline injected around the perimeter of the breast lesion . A h and -held gamma counter was used at surgery to locate the lymph node(s ) receiving drainage from the breast . A sentinel lymph node was identified in 18 of 22 patients . Of these 18 patients , the sentinel lymph node was positive in seven of seven patients , with pathologically verified metastatic breast cancer to at least one lymph node . In three out of seven patients , the sentinel lymph node was the only lymph node with metastatic cancer . In this pilot study of breast cancer patients , we conclude that : ( i ) radiolocalization and selective resection of sentinel lymph nodes is possible ; and ( ii ) the sentinel lymph node appears to predict correctly the status of the remaining axilla . These data justify a larger clinical trial to verify the value of this technique PURPOSE Experience with sentinel node biopsy ( SNB ) after neoadjuvant chemotherapy is limited . We examined the feasibility and accuracy of this procedure within a r and omized trial in patients treated with neoadjuvant chemotherapy . PATIENTS AND METHODS During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27 , several participating surgeons attempted SNB before the required axillary dissection in 428 patients . All underwent lymphatic mapping and an attempt to identify and remove a sentinel node . Lymphatic mapping was performed with radioactive colloid ( 14.7 % ) , with lymphazurin blue dye alone ( 29.9 % ) , or with both ( 54.7 % ) . RESULTS Success rate for the identification and removal of a sentinel node was 84.8 % . Success rate increased significantly with the use of radioisotope ( 87.6 % to 88.9 % ) versus with the use of lymphazurin alone ( 78.1 % , P = .03 ) . There were no significant differences in success rate according to clinical tumor size , clinical nodal status , age , or calendar year of r and om assignment . Of 343 patients who had SNB and axillary dissection , the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients ( 56.0 % ) . Of the 218 patients with negative sentinel nodes , nonsentinel nodes were positive in 15 ( false-negative rate , 10.7 % ; 15 of 140 patients ) . There were no significant differences in false-negative rate according to clinical patient and tumor characteristics , method of lymphatic mapping , or breast tumor response to chemotherapy . CONCLUSION These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy BACKGROUND The sentinel node procedure for breast cancer allows for accurate staging of the axilla while the axillary node dissection can be avoided in patients with no sentinel node metastasis . This study describes those patients in whom an axillary dissection is performed , depending on the outcome of the sentinel node procedure , with particular emphasis on the use of strict criteria for the procedure and its practical limitations . METHODS Preoperative lymphoscintigraphy was performed in 115 consecutive patients . The sentinel nodes were located with the use of a gamma probe and blue dye . Axillary dissection was performed at the same time when the sentinel node procedure was positive by frozen section or not successful by the criteria used . RESULTS The sentinel node procedure was successful in 106 patients , with the sentinel node being both radioactive and blue in 94 % of these patients . The frozen section was positive in 21 of 37 patients with sentinel node metastases . Axillary dissection could be avoided in 69 patients . CONCLUSIONS The triple technique ( with the use of lymphoscintigraphy , the gamma probe , and the blue dye ) gives a high success rate of the sentinel node procedure , even when strict criteria for a successful sentinel node procedure are used . Palpation of the open axilla for metastatic nonsentinel nodes is advocated BACKGROUND Lymphatic mapping and sentinel lymph node ( SLN ) biopsy are new techniques that accurately provide crucial staging information while inflicting far less morbidity than complete axillary dissection . As these techniques continue to gain acceptance , issues such as adequacy of training , certification , and outcomes measures become increasingly important . The purpose of this paper is to report the initial lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute and to provide a detailed description of the technical aspects of lymphatic mapping . STUDY DESIGN From April 1994 to April 1998 , 700 patients with newly diagnosed breast cancers underwent an IRB-approved prospect i ve trial of lymphatic mapping using a combination of Lymphazurin ( USSC , Norwalk , CT ) blue dye and filtered technetium 99m-labeled sulfur-colloid . Failure of the procedure was defined as the inability to detect an SLN by either radiocolloid uptake within a lymph node by the gamma probe or the inability to visualize blue staining of a lymph node . Learning curves were then generated as the failure rate versus serial number of patients for each of the 5 surgeons involved in this study . RESULTS The SLN was identified in 665 of 700 patients ( 95.0 % ) . A total of 1,348 SLNs were successfully removed , of which 238 ( 17.7 % ) were positive for metastatic disease in 176 of 665 patients ( 26.5 % ) . In patients who underwent a complete axillary dissection after SLN biopsy , SLNs were identified in 173 of 186 patients ( 93.0 % ) . Of the 173 patients , 53 patients ( 30.6 % ) had positive SLNs and 120 patients ( 69.4 % ) had negative SLNs . In the 120 patients with negative SLNs , one patient was found to have disease on complete dissection , for a false-negative rate of 0.83 % ( 95 % CI : 0.02 % , 4.6 % ) . A learning curve representing the mean of the 5 surgeons ' experience indicates that on average 23 patients are required by an individual surgeon to achieve a 90 % + /- 4.5 % success rate and 53 patients are required to achieve a 95 % + /- 2.3 % success rate ( p = 0.05 ) . CONCLUSIONS These data vali date lymphatic mapping and SLN biopsy as indispensable tools in the surgical treatment of breast cancer . With adequate multidisciplinary training , these techniques can be readily implemented at institutions treating breast cancer PURPOSE To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node ( SLN ) biopsy in early breast cancer . PATIENTS AND METHODS A prospect i ve r and omized multicentric study was initiated to compare the peritumoral ( PT ) injection site to the periareolar ( PA ) site in 449 patients . RESULTS The detection rate of axillary SLN by lymphoscintigraphy was significantly higher ( P = .03 ) in the PA group ( 85.2 % ) than in the PT group ( 73.2 % ) . Intraoperative detection rate by blue dye and /or gamma probe was similar ( 99.11 % ) in both groups . The rate of SLN detection was somewhat higher in the PA group than in the PT group : 95.6 % versus 93.8 % with blue dye ( P = .24 ) and 98.2 % versus 96.0 % by probe ( P = .16 ) , respectively . The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group , 1.5 versus 1.2 ( P = .001 ) and 1.9 versus 1.7 ( P = .02 ) . The blue and hot concordance was 95.6 % in the PA group and 91.5 % in the PT group ( P = .08 ) . The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group ( P < .0001 ) . CONCLUSION This study strongly vali date s the PA injection technique given the high detection rate ( 99.1 % ) of SLN and the high concordance ( 95.6 % ) between blue dye and the radiotracer , as well as higher significant ex and in vivo counts , improving SLN probe detection Objective : Our objective is to prove that injection of technetium-99 m ( Tc99 ) sulfur colloid in a subareolar manner , after induction of anesthesia , is a safe and effective technique for sentinel lymph node identification in breast cancer patients . Introduction : Preoperative injection of Tc99 and lymphoscintigraphy is st and ardly performed before sentinel lymph node biopsy ( SLNB ) for breast cancer . Blue dye is often used to help guide and confirm the localization but tattoos the breast . This method is limited because of painful injections , variable identification rates , added costs and unnecessary scheduling delays . We hypothesized that intraoperative injection alone by the surgeon of dermal or subareolar Tc99 is practical for the identification of sentinel lymph node in breast cancer . Methods : This is a prospect i ve single institution study that was approved by our institutional review board . All patients with operable breast cancer that were eligible for a SLNB from October 2002 to October 2010 were included in our study population . After induction and before sterile preparation of the operative field 1 mCi of Tc-99 unfiltered was administered by a subareolar injection . In patients where the scar was in the periareolar region or in the upper outer quadrant a dermal injection using 0.25mCi was used . Confirmatory Lymphazurin was also injected early on in this series but became unnecessary later in the study . Site and type of injection , injection time , incision time , and extraction time along with other factors for the purpose s of the study were recorded . Data comparing injection preoperative and intraoperative were collected . Results : Six hundred ninty-nine patients were accrued for a SLNB with an average age 57.1 ± 12.8 ( range 24–92 ) . Seventy-six patients underwent 2 SLNB procedures for a total of 775 intraoperative Tc-99 injections . Six patients underwent intraoperative dermal injection with Tc-99 . The average dose of Tc-99 administered was 1.157 ± 0.230 mCi . The sentinel node was localized in 98.6 % of the cases ( 419/425 ) of subareolar radiotracer alone , 94.8 % ( 326/344 ) in dual injection and 100 % ( 6/6 ) in dermal injection . Average time from injection to incision was 41.20 ± 29.56 minutes for radiotracer injection in subareolar region only . For dermal injections it was 40.83 ± 39.64 minutes . For patients with dual injection of Lymphazurin and radiotracer it was 31.74 ± 24.86 minutes . The average ex vivo count was 6474 ± 8395 for dermal injection , 28,250 ± 69,932 for Tc-99 subareolar injection , and 35,501 ± 97,753 for dual subareolar injection . Intraoperative radiotracer alone incurred a charge of $ 189.00 ; Lymphazurin blue dye added $ 591.40 , whereas preoperative injection had a charge of $ 1257.06 associated with imaging , injection , and interpretation of images . Conclusion : Intraoperative injection of Tc99 alone with a subareolar or dermal injection technique rapidly localizes the sentinel node in breast cancer , is an oncologically sound procedure , is cost effective and facilitates operative room time management OBJECTIVE This prospect i ve multicenter study was performed to assess the reliability of sentinel lymph node ( SLN ) biopsy in breast cancer and to analyze factors potentially influencing success rates . METHODS In 21 departments , SLN biopsy and consecutive axillary lymph node dissection were performed in 814 breast cancer patients . The 80 surgeons involved were free in the choice of lymphography technique . The detection rate and the sensitivity , as well as the impact of lymphography technique , patient selection , technical procedure and learning curves , were evaluated . RESULTS The blue dye technique was used in 137 patients , radiocolloid in 169 patients , and combined blue dye/radiocolloid in 508 patients . The identification rate for the sentinel node was 83.9 % for the entire group and showed a significant dependence on the lymphography technique ( blue dye , 71.6 % ; radiocolloid , 78.8 % ; combined blue dye and radiocolloid , 89.6 % ) . The overall sensitivity in detecting lymph node metastases was 91.3 % . Immunostaining for cytoceratine revealed micrometastases in 19 ( 5.1 % ) of 374 patients in whom H/E staining was negative . The combined subdermal/peritumoral injection of the colloid showed a significantly higher identification rate than subdermal or peritumoral injection alone ( 96.8 % , 84.6 % , 78.6 % ; p < 0.001 ) . There was also a significant higher detection rate in cases of SLN biopsy performed prior to lumpectomy , compared to SLN biopsy following lumpectomy ( 94.7 % versus 82.8 % ; p < 0.001 ) . Furthermore , there was a close correlation between the number of performed examinations and the detection rate . CONCLUSION SLN mapping predicts the axillary lymph node status accurately . Learning curves and several technical features influence the detection rate significantly . However , the false negative rate was independent of experience and injection technique BACKGROUND Sentinel lymph node biopsy ( SLNB ) has become the gold st and ard for axillary staging . Debate remains as to the optimal method of SLN detection . OBJECTIVES Determine whether patients undergoing an SLNB required the addition of isosulfan blue dye to radioisotope when an SLN was identified on a preoperative lymphoscintigram . METHODS A prospect i ve r and omized controlled trial comparing the combination of radioisotope and blue dye versus radioisotope alone was performed between March 2010 and September 2012 . The trial protocol was registered with Current Controlled Trials . Women with clinical ly and radiologically node-negative breast cancer with a positive preoperative lymphoscintigram were eligible for inclusion . RESULTS A total of 667 patients were included in the analysis with 342 patients receiving the combination ( blue dye and radioisotope ) and 325 patients receiving radioisotope alone . The groups were evenly matched both demographically and pathologically . The mean age was 48 years ( 48.3 vs 47.7 years ; P = 0.47 ) , the mean tumour size was 24.2 mm ( 24.3 mm vs 24.1 mm ; P = 0.7 ) and there was no statistically significant difference in the grade of the tumors between the 2 groups ( P = 0.58 ) . There was no difference in the identification rate , nor was that in the number of nodes retrieved between the 2 groups ( P = 0.30 ) . There was no difference in the number of positive lymph nodes that were identified between the 2 groups ( 23.8 % vs 22.1 % ; P = 0.64 ) . CONCLUSIONS This study failed to demonstrate an advantage with the addition of isosulfan blue dye to radioisotope in the identification of the SLN in the presence of a positive preoperative lymphoscintigram BACKGROUND Controversy exists regarding the influence of sentinel lymph node ( SLN ) mapping technique or patient variables on the success rate of SLN mapping . We undertook a prospect i ve study in a single institution series to evaluate multiple variables that could adversely affect SLN identification rates . STUDY DESIGN Data were collected on 174 patients who underwent 177 SLN mapping procedures followed by axillary dissection from October 1996 through January 2000 . Patient demographics , body mass index ( BMI ) , biopsy method , tumor size , palpability , and location were recorded . SLNs were identified by blue dye only ( n = 31 ) , Tc-99 m sulfur colloid only ( n = 34 ) , or combined techniques ( n = 112 ) . Data were analyzed by logistic regression analysis and expressed as the probability of failure to map the SLN . RESULTS SLNs were identified successfully in 150 of 177 procedures ( 85 % ) with a false negative rate of 3.7 % . Mapping success reached 93 % using combination blue dye and isotope . Variables found to adversely affect SLN mapping success and the odds ratio of failure ( OR ) included lower inner quadrant ( LIQ ) location ( OR 35.6 ) , blue dye only ( OR 42.4 ) , BMI > 30 and upper outer quadrant ( UOQ ) location ( OR 14.6 ) , and nonpalpable UIQ location ( OR 25 ) . LIQ location adversely affects mapping success independent of technique , tumor size , or obesity . Obesity and nonpalpability were adverse factors when tumors were located in the UOQ and UIQ , respectively . Age , biopsy technique , and tumor diameter did not affect SLN mapping success . CONCLUSIONS SLN mapping success is influenced by technique and tumor location , with best results achieved using combined techniques and for lesions located in quadrants other than the LIQ . Obesity and tumor palpability influence success in the context of tumor location OBJECTIVES To identify the sentinel lymph node(s ) ( SLN[s ] ) ( the first node[s ] draining the primary tumor in the regional lymphatic basin ) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla . DESIGN A prospect i ve trial . PARTICIPANTS Sixty-two patients with newly diagnosed invasive breast cancers . INTERVENTION Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid . The SLN was identified and removed , followed by a definitive cancer operation , including a complete axillary node dissection . MAIN OUTCOME MEASURE The metastatic distribution in the axilla was determined in patients with occult nodal disease . RESULTS The SLN was successfully identified in 57 ( 92 % ) of 62 patients using the 2 lymphatic mapping procedures . After localization , 18 patients ( 32 % ) were found to have metastatic disease , and the SLN tested positive in all 18 patients . There were no " skip " metastases , defined as an SLN that tested negative with higher nodes that tested positive . In 12 ( 67 % ) of 18 patients with metastatic disease , the SLN was the only site of disease . The metastatic distribution significantly favored SLN involvement . Among subjects with discordant nodal involvement , the probability of observing the distribution of SLN involvement by chance is very small ( P<.001 ) . CONCLUSIONS This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes . The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes , potentially increasing the yield of positive dissections and the accuracy of staging Background The identification rate of sentinel lymph nodes ( SLNs ) is variable because numerous different methods employing different tracers have been used for sentinel lymph node detection . The aim of this study was to determine the optimal technique for sentinel lymph node biopsy ( SLNB ) . Methods From May 1999 to December 2001 , SLNB was performed for 376 patients with Tl-3 and NO-1 primary breast cancer using blue dye alone , radioisotope ( RI ) alone and combination of RI and blue dye . Two hundred sixty-eight patients underwent SLNB using blue dye alone . They were divided into 4 groups ( Group A : n = 50 ; peritumoral injection , Group B : n = 83 ; the first half to receive subareolar injection , Group C : n = 83 ; the second half to receive subareolar injection , and Group D : n = 52 ; small incision according to an axillary skin l and mark ) . One hundred eight patients underwent SLNB using RI . Tin colloid was used in 49 cases ( Tin Colloid Group ) and phytate in 59 cases ( Phytate Group ) . Among them , 29 patients underwent injection of RI alone and 79 patients received a combination of RI and blue dye . Results The identification rates of SLN using blue dye alone were 60 % , 82 % , 92 % and 79 % in Groups A , B , C and D , respectively . The identification rates of SLN in patients receiving RI alone and in those receiving combination of RI and blue dye were 40 % and 89 % , respectively , in Tin Colloid Group , and 92 % and 94 % , respectively , in Phytate Group . Conclusion When using blue dye alone , subareolar injection provided a better identification rate than peritumoral injection . The combination of peritumoral phytate and subareolar blue dye provided the best identification rate ( 94 % ) in all the groups . The combination of intraparenchymal phytate and subareolar blue dye was the most efficient technique for sentinel node biopsy in breast cancer patients IMPORTANCE Sentinel lymph node ( SLN ) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection ( ALND ) for patients with clinical ly node-negative ( cN0 ) breast cancer . The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies . OBJECTIVE To determine the false-negative rate ( FNR ) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer . DESIGN , SETTING , AND PATIENTS The American College of Surgeons Oncology Group ( ACOSOG ) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4 , N1 through N2 , M0 breast cancer and received neoadjuvant chemotherapy . Following chemotherapy , patients underwent both SLN surgery and ALND . Sentinel lymph node surgery using both blue dye ( isosulfan blue or methylene blue ) and a radiolabeled colloid mapping agent was encouraged . MAIN OUTCOMES AND MEASURES The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease . We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10 % , the rate expected for women undergoing SLN surgery who present with cN0 disease . RESULTS Seven hundred fifty-six women were enrolled in the study . Of 663 evaluable patients with cN1 disease , 649 underwent chemotherapy followed by both SLN surgery and ALND . An SLN could not be identified in 46 patients ( 7.1 % ) . Only 1 SLN was excised in 78 patients ( 12.0 % ) . Of the remaining 525 patients with 2 or more SLNs removed , no cancer was identified in the axillary lymph nodes of 215 patients , yielding a pathological complete nodal response of 41.0 % ( 95 % CI , 36.7%-45.3 % ) . In 39 patients , cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND , result ing in an FNR of 12.6 % ( 90 % Bayesian credible interval , 9.85%-16.05 % ) . CONCLUSIONS AND RELEVANCE Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined , the FNR was not found to be 10 % or less . Given this FNR threshold , changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00881361 |
11,123 | 28,745,067 | Results indicated that elements of informed consent unique to biobanking were poorly understood .
Increased disclosures , values-clarification , and presenting information via multiple modalities may facilitate underst and ing . | Nurses are increasingly asked to obtain consent from participants for biobanking studies .
Biobanking has added unique complexities to informed consent .
The purpose of this systematic review was to evaluate participants ’ level of underst and ing of the information presented during the informed consent process unique to the donation of biological specimens for research . | BACKGROUND The informed consent of participants is ethically and legally required for most research involving human subjects . However , st and ardized methods for assessing the adequacy of informed consent to research are lacking . METHODS AND RESULTS We design ed a brief question naire , the Quality of Informed Consent ( QuIC ) , to measure subjects ' actual ( objective ) and perceived ( subjective ) underst and ing of cancer clinical trials . The QuIC incorporates the basic elements of informed consent specified in federal regulations , assesses the therapeutic misconception ( the belief that all aspects of a clinical trial are design ed to directly benefit the subject ) , and employs the language and structure of the new National Cancer Institute template for informed consent documents . We modified the QuIC after receiving feedback from pilot tests with cancer research subjects , as well as validation from two independent expert panels . We then sent the QuIC to 287 adult cancer patients enrolled on phase I , II , or III clinical trials . Two hundred seven subjects ( 72 % ) completed the QuIC . To assess test-retest reliability , a r and om sample of 32 respondents was selected , of whom 17 ( 53 % ) completed the question naire a second time . The test-retest reliability was good with intraclass correlation coefficients of.66 for tests of objective underst and ing and .77 for tests of subjective underst and ing . The current version of the QuIC , which consists of 20 questions for objective underst and ing and 14 questions for subjective underst and ing , was tested for time and ease of administration in a sample of nine adult cancer patients . The QuIC required an average of 7.2 minutes to complete . CONCLUSIONS The QuIC is a brief , reliable , and valid question naire that holds promise as a st and ardized way to assess the outcome of the informed consent process in cancer clinical trials Objective . Health professionals must enable patients to make informed decisions about health care choices through unbiased presentation of all options . This study examined whether presenting the decision as “ opportunity ” rather than “ choice ” biased individuals ’ preferences in the context of trial participation for cancer treatment . Methods . Self- selecting healthy women ( N = 124 ) were r and omly assigned to the following decision frames : opportunity to take part in the trial ( opt-in ) , opportunity to be removed from the trial ( opt-out ) , and choice to have st and ard treatment or take part in the trial ( choice ) . The computer-based task required women to make a hypothetical choice about a real-world cancer treatment trial . The software presented the framed scenario , recorded initial preference , presented comprehensive and balanced information , traced participants ’ use of information during decision making , and recorded final decision . A posttask paper question naire assessed perceived risk , attitudes , subjective norm , perceived behavioral control , and satisfaction with decision . Results . Framing influenced women ’s immediate preferences . Opportunity frames , whether opt-in or opt-out , introduced a bias as they discouraged women from choosing st and ard treatment . Using the choice frame avoided this bias . The opt-out opportunity frame also affected women ’s perceived social norm ; women felt that others endorsed the trial option . The framing bias was not present once participants had had the opportunity to view detailed information on the options within a patient decision aid format . There were no group differences in information acquisition and final decisions . Sixteen percent changed their initial preference after receiving full information . Conclusions . A “ choice ” frame , where all treatment options are explicit , is less likely to bias preferences . Presentation of full information in parallel , option-by-attribute format is likely to “ de-bias ” the decision frame . Tailoring of information to initial preferences would be ill-advised as preferences may change following detailed information Purpose : To determine the individual and combined effects of a simplified form and a review /retest intervention on biobanking consent comprehension . Methods : We conducted a national online survey in which participants were r and omized within four educational strata to review a simplified or traditional consent form . Participants then completed a comprehension quiz ; for each item answered incorrectly , they review ed the corresponding consent form section and answered another quiz item on that topic . Results : Consistent with our first hypothesis , comprehension among those who received the simplified form was not inferior to that among those who received the traditional form . Contrary to expectations , receipt of the simplified form did not result in significantly better comprehension compared with the traditional form among those in the lowest educational group . The review /retest procedure significantly improved quiz scores in every combination of consent form and education level . Although improved , comprehension remained a challenge in the lowest-education group . Higher quiz scores were significantly associated with willingness to participate . Conclusion : Ensuring consent comprehension remains a challenge , but simplified forms have virtues independent of their impact on underst and ing . A review /retest intervention may have a significant effect , but assessing comprehension raises complex questions about setting thresholds for underst and ing and consequences of not meeting them . Genet Med advance online publication 13 October 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 Background Although the amount of detail in informed consent documents has increased over time and the documents have therefore become very long , there is little research on whether longer informed consent documents actually result in ( 1 ) better informed research subjects or ( 2 ) higher consent rates . We therefore conducted an add-on r and omized controlled trial to the Takashima Study , a prospect i ve Japanese population -based genetic cohort study , to test the hypothesis that a shorter informed consent form would satisfy both of the above goals . Methods St and ard ( 10 459 words , 11 pages ) and short ( 3602 words , 5 pages ) consent forms in Japanese were developed and distributed using cluster-r and omization to 293 potential cohort subjects living in 9 medico-social units and 288 subjects in 8 medico-social units , respectively . Results Few differences were found between the 2 groups with regard to outcome measures , including participants ’ self-perceived underst and ing , recall of information , concerns , voluntariness , trust , satisfaction , sense of duty , and consent rates . Conclusions A short informed consent form was no less valid than a st and ard form with regard to fulfilling ethical requirements and securing the scientific validity of research Purpose : The potential of interactive multimedia to improve biobank informed consent has yet to be investigated . The aim of this study was to test the separate effectiveness of interactivity and multimedia at improving participant underst and ing and confidence in underst and ing of informed consent compared with a st and ard , face-to-face ( F2F ) biobank consent process . Methods : A 2 ( face-to-face versus multimedia ) × 2 ( st and ard versus enhanced interactivity ) experimental design was used with 200 patients r and omly assigned to receive informed consent . All patients received the same information provided in the biobank ’s nine-page consent document . Results : Interactivity ( F(1,196 ) = 7.56 , P = 0.007 , partial η2 = 0.037 ) and media ( F(1,196 ) = 4.27 , P = 0.04 , partial η2 = 0.021 ) independently improved participants ’ underst and ing of the biobank consent . Interactivity ( F(1,196 ) = 6.793 , P = 0.01 , partial η2 = 0.033 ) , but not media ( F(1,196 ) = 0.455 , not significant ) , result ed in increased participant confidence in their underst and ing of the biobank ’s consent material s. Patients took more time to complete the multimedia condition ( mean = 18.2 min ) than the face-to-face condition ( mean = 12.6 min ) . Conclusion : This study demonstrated that interactivity and multimedia each can be effective at promoting an individual ’s underst and ing and confidence in their underst and ing of a biobank consent , albeit with additional time investment . Research ers should not assume that multimedia is inherently interactive , but rather should separate the two constructs when study ing electronic consent . Genet Med 18 1 , 57–64 Purpose : Federal regulations and best practice guidelines identify categories of information that should be communicated to prospect i ve biobank participants during the informed consent process . However , uncertainty remains about which of this information participants must underst and to provide valid consent . Methods : We conducted a Delphi process to define “ adequate comprehension ” in the context of biobanking consent . The process involved an iterative series of three online surveys of a diverse panel of 51 experts , including genome scientists , biobank managers , ethics and policy experts , and community and participant representatives . We sought consensus ( > 70 % agreement ) concerning what specific details participants should know about 16 biobank consent topics . Results : Consensus was achieved for 15 of the 16 consent topics . The exception was the comprehension needed regarding the Genetic Information Nondiscrimination Act . Conclusion : Our Delphi process was successful in identifying a concise set of key points that prospect i ve participants must grasp to provide valid consent for biobanking . Specifying the level of knowledge sufficient for individuals to make an informed choice provides a basis for improving consent forms and processes , as well as an absolute metric for assessing the effectiveness of other interventions to improve comprehension . Genet Med 17 3 , 226–233 OBJECTIVE Patients are commonly presented with complex documents that they have difficulty underst and ing . The objective of this study was to design and evaluate an animated computer agent to explain research consent forms to potential research participants . METHODS Subjects were invited to participate in a simulated consent process for a study involving a genetic repository . Explanation of the research consent form by the computer agent was compared to explanation by a human and a self- study condition in a r and omized trial . Responses were compared according to level of health literacy . RESULTS Participants were most satisfied with the consent process and most likely to sign the consent form when it was explained by the computer agent , regardless of health literacy level . Participants with adequate health literacy demonstrated the highest level of comprehension with the computer agent-based explanation compared to the other two conditions . However , participants with limited health literacy showed poor comprehension levels in all three conditions . Participants with limited health literacy reported several reasons , such as lack of time constraints , ability to re-ask questions , and lack of bias , for preferring the computer agent-based explanation over a human-based one . CONCLUSION Animated computer agents can perform as well as or better than humans in the administration of informed consent . PRACTICE IMPLICATION S Animated computer agents represent a viable method for explaining health documents to patients Using examples from psychiatric research , the authors explore the ethical dilemma of the " therapeutic misconception , " where , despite explanation , patient-subjects believe that research protocol s are design ed to benefit them directly rather than to test or compare treatment methods . Even potential subjects who demonstrate an underst and ing of r and omization , double-blinded studies , and the use of placebos frequently persist in a belief that they purpose ly will receive the treatment most likely to benefit them . They expect the st and ards of personal care that characterize the therapeutic relationship to carry over to the clinical trial , failing to underst and that the need for valid research results makes this impossible . Appelbaum et al. suggest ways in which patients can be made to underst and the differences between treatment and research , and the disadvantages and advantages of participation in the latter As genomic research ers are urged to openly share generated sequence data with other research ers , it is important to examine the utility of informed consent documents and processes , particularly as these relate to participants ' engagement with and recall of the information presented to them , their objective or subjective underst and ing of the key elements of genomic research ( e.g. , data sharing ) , as well as how these factors influence or mediate the decisions they make . We conducted a r and omized trial of three experimental informed consent documents ( ICDs ) with participants ( n = 229 ) being recruited to genomic research studies ; each document afforded varying control over breadth of release of genetic information . Recall and underst and ing , their impact on data sharing decisions , and comfort in decision making were assessed in a follow-up structured interview . Over 25 % did not remember signing an ICD to participate in a genomic study , and the majority ( 54 % ) could not correctly identify with whom they had agreed to share their genomic data . However , participants felt that they understood enough to make an informed decision , and lack of recall did not impact final data sharing decisions or satisfaction with participation . These findings raise questions about the types of information participants need in order to provide valid informed consent , and whether subjective underst and ing and comfort with decision making are sufficient to satisfy the ethical principle of respect for persons BACKGROUND Many research studies conducted today in critical care have a genomics component . Patients ' surrogates asked to authorize participation in genomics research for a loved one in the intensive care unit may not be prepared to make informed decisions about a patient 's participation in the research . OBJECTIVES To examine the effectiveness of a new , computer-based education module on surrogates ' underst and ing of the process of informed consent for genomics research . METHODS A pilot study was conducted with visitors in the waiting rooms of 2 intensive care units in a Midwestern tertiary care medical center . Visitors were r and omly assigned to the experimental ( education module plus a sample genomics consent form ; n = 65 ) or the control ( sample genomics consent form only ; n = 69 ) group . Participants later completed a test on informed genomics consent . RESULTS Underst and ing the process of informed consent was greater ( P = .001 ) in the experimental group than in the control group . Specifically , compared with the control group , the experimental group had a greater underst and ing of 8 of 13 elements of informed consent : intended benefits of research ( P = .02 ) , definition of surrogate consenter ( P= .001 ) , withdrawal from the study ( P = .001 ) , explanation of risk ( P = .002 ) , purpose of the institutional review board ( P = .001 ) , definition of substituted judgment ( P = .03 ) , compensation for harm ( P = .001 ) , and alternative treatments ( P = .004 ) . CONCLUSIONS Computer-based education modules may be an important addition to conventional approaches for obtaining informed consent in the intensive care unit . Preparing patients ' family members who may consider serving as surrogate consenters is critical to facilitating genomics research in critical care |
11,124 | 17,047,006 | intravenous rtPA-treated stroke patients of > /=80 years of age have a less favourable outcome than younger ones .
Imbalances in predictive baseline variables to the disadvantage of the older patients may contribute to this finding .
Compared with the younger cohort , rtPA-treated stroke patients aged > /=80 years do not seem exceedingly prone to sICH .
Thus , there is scope for benefit from thrombolysis for the older age group . | OBJECTIVE elderly stroke patients were excluded or underrepresented in the r and omised controlled trials of intravenous thrombolysis with recombinant tissue plasminogen activator ( rtPA ) applied within 3 h. Cohort studies comparing intravenous rtPA in stroke patients of > /=80 versus < 80 years of age were limited by small sample sizes and yielded conflicting results .
Thus , we performed a systematic review across all such studies . | 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 Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials , no generally acceptable method exists to train and certify investigators to use the instrument consistently . We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably . Methods We devised a two-camera videotape method that optimizes the visual presentation of examination findings . We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients , also on videotape . We tabulated the evaluations , devised a scoring system , and calculated measures of interobserver agreement among the participants in this study . Results We trained and certified 162 investigators . We found moderate to excellent agreement on most Stroke Scale items ( unweighted K>0.60 ) . TWO items , facial paresis and ataxia , exhibited poor agreement ( unweighted K<0.40 ) and should be revised in future editions of the scale . Performance improved with video training compared with previous studies . Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability . Conclusions Video training and certification is a practical and effective method to st and ardize the use of examination scales . Two cameras must be used during the taping of patients to accurately present the clinical findings . This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers Introduction . Systemic thrombolysis with intravenous recombinant tissue plasminogen activator ( rtPA ) for acute ischemic stroke had been licensed for patients up to 75 years in age in many European countries and was recently extended to 80 years . This age restriction results from the potential higher risk of cerebral bleeding in the elderly . The major rtPA trials included only 42 patients above 80 years showing a potential benefit from treatment . Further data is still rare . Methods . Using our stroke data base we identified all patients beyond 75 years with middle cerebral artery ischemia treated with intravenous rtPA in our stroke unit from 02/1999 until 07/2004 . Clinical course and outcome until day 5 in addition to mortality after 3 and 6 months were analysed . Results . Twenty-nine patients ( 80.8 ± 4 years , 16 of them over 80 years old ) met the inclusion criteria representing 21.2 % of those receiving thrombolytic therapy . The median NIH-SS score on admission was 14 points . On day 5 after thrombolysis , 13/29 showed a good recovery ( NIH-SS improvement ≥4 pts ) . The remaining exhibited only small or no benefit ( n = 11 ) , deterioration ( n = 3 ) or died ( n = 2 ) . A total of 3/29 patients developed non-symptomatic parenchymal hemorrhage or hemorrhagic transformation . One patient died due to space-occupying cerebral hemorrhage . Extracerebral bleeding was found in 3/29 requiring substitution in one . One other died for primary cardiac reasons . Median NIH-SS on day 5 was 10 points . Mortality after 3 and 6 months was 20.7 % . We did not find factors predicting clinical outcome . Most importantly , there was no significant difference regarding outcome in patients 76–80 vs. 81–87 years old . Discussion . Intravenous rtPA result ed in good neurological in-hospital outcome in almost 45 % and six-months survival of almost 80 % of the patients beyond 75 years . In 10.3 % non-symptomatic and in 3.4 % symptomatic cerebral bleeding was found . Thus , seniors beyond 75 and even beyond 80 years in good medical condition may benefit from systemic treatment with rtPA . Prospect i ve studies are needed to clarify which part of the senior population might be most eligible for systemic thrombolysis Background and Purpose — Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator ( tPA ) in stroke patients . Methods — We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke ( ATLANTIS ) study who were r and omized to receive intravenous tPA or placebo within 3 hours of symptom onset . Results — Despite a significant increase in the rate of symptomatic intracranial hemorrhage , tPA-treated patients were more likely to have a very favorable outcome ( score of ≤1 ) on the National Institutes of Health Stroke Scale at 90 days ( P = 0.01 ) . Conclusions — These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset 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 Abstract . Objective : Disability and mortality represent the most relevant clinical outcome after acute ischemic stroke . However , vali date d and comprehensive prognostic models for recovery have not been developed . An accurate model including all previously suggested independent outcome predictors could improve the design and analysis of clinical trials . We therefore developed prognostic models for functional dependence and death after 100 days in a large cohort of stroke patients . Methods : From the German Stroke Data base , 1754 prospect ively collected records of patients with acute ischemic stroke were used for the development of prognostic models . Intubated patients and patients with low functional status before stroke were excluded . Functional independence was defined as a Barthel Index ≥95 after 100 days . Prognostic factors assessable within 72 hours after admission were identified by a systematic literature review . The final models of binary logistic regression analyses were internally vali date d and calibrated . Results : The result ing cross-vali date d and calibrated models correctly classified more than 80 % of the patients and yielded the following prognostic factors for functional independence : Age , right and left arm paresis at admission , NIH-Stroke Scale at admission , Rankin Scale 48–72 hours later , gender , prior stroke , diabetes , fever , lenticulostriate infa rct ion , neurological complications . The following variables were identified as prognostic factors for death : Age , NIH-Stroke Scale at admission , and fever . Conclusions : Our work gives an important insight into prognostic factors after acute ischemic stroke and presents predictive models with high prognostic accuracy . Together with a prospect i ve validation study , currently underway , we hence hope to improve the prediction of functional outcome after ischemic 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 Acute ischaemic stroke is common in older people . There is one licensed acute treatment , intravenous recombinant tissue plasminogen activator , but little information is available on its safety in over 80 year olds . DESIGN Review of prospect ively collected data on 62 consecutive patients , aged 80 years and over , treated with recombinant tissue plasminogen activator in a tertiary centre . METHODS Admission demographic data , clinical and CT stroke severity , symptomatic haemorrhage rate and other complications were compared between patients who were dead at 3 months and those who survived . Discharge location and functional scores outcome were review ed . The results were compared to those of other studies . RESULTS The in-hospital death rate was 24.2 % and 3 month mortality 32.8 % . Patients that died had higher stroke severity scores at presentation ( NIHSS 20 versus 16 , P = 0.04 ) . Six patients ( 9.7 % ) suffered symptomatic intracranial haemorrhage ( SICH ) , three were classified as fatal ( 4.8 % ) . SICH was significantly associated with death by 3 months ( P = 0.02 ) . There were no other serious bleeding complications . The SICH rate is similar to that from other thrombolytic studies and the mortality rate is similar to the natural history of stroke in older population s. CONCLUSION Older patients have high mortality and morbidity from stroke . Older patients should not be excluded from recombinant tissue plasminogen activator treatment on the basis of age alone BACKGROUND Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials . We performed a r and omized , double-blind trial of intravenous recombinant tissue plasminogen activator ( t-PA ) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke . METHODS The trial had two parts . Part 1 ( in which 291 patients were enrolled ) tested whether t-PA had clinical activity , as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale ( NIHSS ) or the resolution of the neurologic deficit within 24 hours of the onset of stroke . Part 2 ( in which 333 patients were enrolled ) used a global test statistic to assess clinical outcome at three months , according to scores on the Barthel index , modified Rankin scale , Glasgow outcome scale , and NIHSS : RESULTS In part 1 , there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours , although a benefit was observed for the t-PA group at three months for all four outcome measures . In part 2 , the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed ( global odds ratio for a favorable outcome , 1.7 ; 95 percent confidence interval , 1.2 to 2.6 ) . As compared with patients given placebo , patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales . Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo ( P < 0.001 ) . Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group ( P = 0.30 ) . CONCLUSIONS Despite an increased incidence of symptomatic intracerebral hemorrhage , treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months BACKGROUND AND PURPOSE We sought to identify variables associated with intracerebral hemorrhage in patients with acute ischemic stroke who receive tissue plasminogen activator ( t-PA ) . METHODS We performed subgroup analyses of data from a r and omized , double-blind , placebo-controlled trial of intravenous t-PA administered to stroke patients within 3 hours of onset . Using multivariable regression modeling procedures , we assessed the relationship of baseline and after-treatment variables with symptomatic and asymptomatic intracerebral hemorrhage during the first 36 hours after treatment . RESULTS Overall , t-PA-treated patients had an increase in the absolute risk of symptomatic intracerebral hemorrhage of 6 % and a decrease in the absolute risk of 3-month mortality of 4 % compared with placebo-treated patients . The only variables independently associated with an increased risk of symptomatic intracerebral hemorrhage in the final multivariable logistic regression model for the 312 t-PA-treated patients were the severity of neurological deficit as measured by the National Institutes of Health Stroke Scale score ( five categories ; odds ratio [ OR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.2 to 2.9 ) and brain edema ( defined as acute hypodensity ) or mass effect by CT before treatment ( OR , 7.8 ; 95 % CI , 2.2 to 27.1 ) . This final model correctly predicted those t-PA-treated patients who would or would not have a symptomatic hemorrhage with only 57 % efficiency . In the subgroup of patients with a severe neurological deficit , t-PA-treated patients were more likely than placebo-treated patients to have a favorable 3-month outcome ( adjusted OR based on multiple outcomes , 4.3 ; 95 % CI , 1.6 to 11.9 ) . These results were similar for the subgroup with edema or mass effect by CT ( adjusted OR , 3.4 ; 95 % CI , 0.6 to 20.7 ) . The likelihood of severe disability or death was similar for t-PA- and placebo-treated patients with these two baseline characteristics . CONCLUSIONS Despite a higher rate of intracerebral hemorrhage , patients with severe strokes or edema or mass effect on the baseline-CT are reasonable c and i date s for t-PA , if it is administered within 3 hours of onset Aim : Stroke is common in older people . The objective of the study was to determine if older stroke patients have a higher mortality and disability compared with younger patients for comparable stroke severity and pathology and whether there is an explanation for the difference . Methods : A prospect i ve study was undertaken in 296 consecutive patients admitted with acute stroke . Patients were studied for neurological features , pre-stroke functional disability , severity of stroke defined by stroke syndromes and pathology of stroke on CT scans ( 202 patients ) . Post-stroke disability was defined according to the functional status within 72 h of admission . A record was made of the intercurrent illness while the patients were in acute wards and of the risk factors . Patients were dichotomised into two age groups : younger group – up to 75 years ( 163 patients ) and older group – over 75 years ( 133 patients ) . Outcome was measured according to ( 1 ) discharge status from acute wards , i.e. , dead or alive , and ( 2 ) mortality at 3 months . Results : Although there was no significant difference in severe clinical stroke syndromes ( p = 0.72 ) , CT scan features ( p = 0.68 ) and pyrexia ( 0.38 ) between the two age groups , the older patients had significantly more disabling strokes as defined on Barthel Index ( p = 0.015 ) and a higher mortality in the acute phase ( p < 0.01 ) and at 3 months ( p = 0.001 ) . The older stroke patients had more severe pre-stroke disability ( p < 0.001 ) and more severe neurological impairment for similar stroke severity and pathology . Early mortality was more influenced by pre-stroke global health than age whereas 3-month mortality was influenced by age to the exclusion of all other known prognostic factors . Conclusion : The older stroke patients have more disabling stroke and an increased mortality for a similar spectrum of stroke severity and pathology . The explanation for higher mortality of the older patients is the poor pre-stroke health and higher immediate post-stroke disability |
11,125 | 23,712,349 | Glycated hemoglobin level had poorer test characteristics than fasting plasma glucose level or the OGCT .
The OGCT and fasting plasma glucose level ( at a threshold of 4.7 mmol/L [ 85 mg/dL ] ) by 24 weeks ' gestation are good at identifying women who do not have GDM .
The OGCT is better at identifying women who have GDM . | BACKGROUND A 50-g oral glucose challenge test ( OGCT ) is a widely accepted screening method for gestational diabetes mellitus ( GDM ) , but other options are being considered .
PURPOSE To systematic ally review the test characteristics of various screening methods for GDM across a range of recommended diagnostic glucose thresholds . | In this study , we assessed maternal-fetal outcomes in untreated patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes mellitus ( GDM ) , examined the relationship between birth weight and mode of delivery among women with untreated borderline GDM , treated overt GDM , and normoglycemia , and established more efficient screening strategies for detection of GDM . This was a prospect i ve analytic cohort study in which nondiabetic women aged > or = 24 years were eligible for enrollment . A 50-g glucose challenge test ( GCT ) and a 100-g oral glucose tolerance test ( OGTT ) were administered at 26 and 28 weeks gestational age , respectively . Risk factors for unfavorable maternal-fetal outcomes were recorded . Time since the last meal prior to the screening test was recorded , as well . Caregivers and patients were blinded to glucose values except when test results met the National Diabetes Data Group criteria for GDM . Maternal and fetal outcomes , including the mode of the delivery , were recorded in the postpartum period . Of 4,274 patients screened , 3,836 ( 90 % ) continued to the diagnostic oral glucose tolerance test . GDM was seen in 145 women . Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean section , preeclampsia , macrosomia , and need for phototherapy , as well as an increased length of maternal and neonatal hospital stay . Multivariate analysis showed that increasing carbohydrate intolerance remained an independent predictor for various unfavorable outcomes , but the strength of the associations was diminished . Compared with normoglycemic control subjects , the untreated borderline GDM group had increased rates of macrosomia ( 28.7 vs. 13.7 % , P < 0.001 ) and cesarean delivery ( 29.6 vs. 20.2 % , P = 0.03 ) . Usual care of known GDM patients normalized birth weights , but the cesarean delivery rate was about 33 % , whether macrosomia was present or absent . An increased risk of cesarean delivery among treated patients compared with normoglycemic control subjects persisted after adjustment for multiple maternal risk factors . As for the screening tests , time since the last meal had a marked effect on mean plasma glucose . Receiver operating characteristic curve analysis allowed the selection of the most efficient cut points for the GCT based on the time since the last meal . These cut points were 8.2 , 7.9 , and 8.3 mmol/l ( 1 mmol/l = 18.015 mg/dl ) for elapsed postpr and ial time of < 2 , 2 - 3 , and > 3 h , respectively . With this change from the current threshold of 7.8 mmol/l , the number of patients with a positive screening test dropped from 18.5 to 13.7 % . There was an increase in positive predictive value from 14.4 to 18.7 % . The overall rate of patient misclassification fell from 18.0 to 13.1 % . In conclusion , increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a grade d increase in adverse maternal and fetal outcomes . Infant macrosomia is an important factor in high cesarean delivery rates for women with untreated borderline GDM . Although detection and treatment of GDM normalizes birth weights , rates of cesarean delivery remain inexplicably high . Recognition of GDM may lead to a lower threshold for surgical delivery . The efficiency of screening for GDM can be enhanced by adjusting the current GCT threshold of 7.8 mmol/l to new values related to time since the last meal before screening . Further analyses are underway to eluci date whether maternal risk factors can be used to achieve additional efficiency gains in screening OBJECTIVE Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes . STUDY DESIGN We conducted a prospect i ve analytic cohort study in which nondiabetic women aged > or = 24 years , receiving prenatal care in three Toronto teaching hospitals , were eligible for enrollment . A glucose challenge test and an oral glucose tolerance test were administered at 26 and 28 weeks ' gestation , respectively ; risk factors for unfavorable maternal-fetal outcomes were recorded . Caregivers and patients were blinded to glucose values except when test results met the current criteria for gestational diabetes . RESULTS Of 4274 patients screened , 3836 ( 90 % ) continued to the diagnostic oral glucose tolerance test . The study cohort was formed by the 3637 ( 95 % ) patients without gestational diabetes , carrying singleton fetuses . Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean sections , preeclampsia , macrosomia , and need for phototherapy , as well as an increased length of maternal and neonatal hospital stay . Multivariate analysis showed that increasing carbohydrate intolerance is an independent predictor for various unfavorable outcomes . CONCLUSION Increasing maternal carbohydrate intolerance in pregnant women without gestational diabetes is associated with a grade d increase in adverse maternal-fetal outcomes CONTEXT AND OBJECTIVE Lack of consensus about which screening tests to use for gestational diabetes mellitus ( GDM ) and difficulties in performing the gold-st and ard diagnostic test , the 100-g glucose tolerance test ( 100-g GTT ) , justify comparison with alternatives . The aim was to compare this with two other screening tests : combined fasting glucose with risk factors ( FG + RF ) and 50-g GTT . DESIGN AND SETTING Prospect i ve longitudinal cohort study in the Hospital School of Universidade Federal de Mato Grosso do Sul . METHODS The three tests were performed independently on 341 pregnant women . Sensitivity ( S ) , specificity ( Sp ) , positive ( PPV ) and negative ( NPV ) predictive values , positive ( PLR ) and negative ( NLR ) likelihood ratios , and false-positive ( FP ) and false-negative ( FR ) rates obtained with FG + RF and 50-g GTT were compared with values from 100-g GTT . The average one-hour post-intake glucose levels ( 1hPG ) with 50-g and 100-g were compared . Students t test was used in the statistical analysis . RESULTS FG + RF led more pregnant women ( 53.9 % ) to diagnostic confirmation than did 50-g GTT ( 14.4 % ) . The tests were equivalent for S ( 86.4 and 76.9 % ) , PPV ( 98.7 and 98.9 % ) , NLR ( 0.3 and 0.27 ) and FR ( 15.4 and 23.1 % ) . Average 1hPG values were similar : 50-g GTT = 106.8 mg/dl and 100-g GTT = 107.5 mg/dl . CONCLUSION Diagnostic efficiency with simplicity , practicality and low cost make FG + RF more appropriate for screening for GDM . The equivalence of 1hPG allows a new , cheaper and less uncomfortable protocol to be proposed for screening and diagnosing GDM BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life OBJECTIVE The International Association of Diabetes and Pregnancy Study Groups ( IADPSG ) has proposed new criteria for the diagnosis of gestational diabetes mellitus ( GDM ) . The aim of this study was to compare the prevalence of GDM when IADPSG criteria were used with the prevalence when the current Australasian Diabetes in Pregnancy Society ( ADIPS ) criteria were used . DESIGN , SETTING AND PARTICIPANTS This was a prospect i ve study over a 6-month period , examining the results of all glucose tolerance tests ( GTTs ) conducted for the diagnosis of GDM in Wollongong , a city using the public and private sectors . MAIN OUTCOME MEASURES The prevalence of GDM using the existing ( ADIPS ) and the proposed ( IADPSG ) criteria . RESULTS There were 1275 evaluable GTTs ( 571 public and 704 private ) . Using the current ADIPS diagnostic criteria , the prevalence of GDM was 8.6 % ( public ) , 10.5 % ( private ) and 9.6 % ( overall ) . Using the proposed IADPSG criteria , the prevalence of GDM was 9.1 % ( public ) , 16.2 % ( private ) and 13.0 % ( overall ) . CONCLUSIONS The proposed IADPSG criteria would increase the prevalence of GDM from 9.6 % to 13.0 % ( P < 0.001 ) . In our study in the Wollongong area , which has a population with a predominantly white background , this increase came mainly from older women attending a private pathology provider . Data from both the public and private sectors need to be included in any discussion on the change in prevalence of GDM OBJECTIVE The objective of this study was to compare 2-hour postpr and ial glucose measurements with the st and ard 1-hour , 50 gm glucola screen as a predictor of gestational diabetes . STUDY DESIGN In this prospect i ve study , 448 patients were screened for gestational diabetes mellitus after 20 weeks ' gestation . Each patient was instructed to ingest a meal containing at least 100 gm of carbohydrate , and 2 hours later a plasma glucose level was obtained . Shortly after , each patient was given 50 gm glucola followed by a 1-hour glucose measurement . If either screen showed a result of 140 mg/dl or more , a formal 3-hour glucose tolerance test was done . Data were analyzed with use of the receiver operating characteristic curve . RESULTS Of the 448 patients screened , 39 ( 8.7 % ) had a screening result of 140 mg/dl or greater and 16 ( 3.6 % ) of these had gestational diabetes mellitus . The receiver operating characteristic curve showed that the 1-hour glucose screen was more predictive of gestational diabetes than the postmeal assessment . The area under the receiver operating characteristic curve ( plus or minus the SEM ) for the 1-hour glucose test was 0.746 + /- 0.086 ( p < 0.005 ) whereas the 2-hour postpr and ial test produced an area of 0.524 + /- 0.097 ( p = NS ) . The range of optimal 1-hour glucola discriminatory values was 182 to 190 mg/dl . Thus the critical cutoff value of the 1-hour glucola test that minimizes false-positive results and maximizes true-positive screening for gestational diabetes is 182 mg/dl or greater . CONCLUSIONS The 1-hour glucola test is a reliable screening test for gestational diabetes mellitus whereas the 2-hour post-pr and ial test is not OBJECTIVES To vali date a diagnostic test for gestational diabetes which predicts the risk of macrosomia . METHODS A prospect i ve study was carried out among 354 women at risk for gestational diabetes to compare two glucose tests diagnosing pregnancies at risk of macrosomia . The " practical " test consisted in glucose measurement in the fasting state and two hours after an usual breakfast and the " reference " test was the test proposed in France ( O'Sullivan test with or without a 100 g oral glucose tolerance test ) . Both tests were made between the 24(th ) and 28(th ) week of gestation . Women at high risk for macrosomia were treated . The first assessment criterion was macrosomia ( babies large for gestational age ) . Because of the presence of women treated for gestational diabetes in our sample , the sensitivity and specificity of the tests in diagnosing pregnancies at risk of macrosomia were calculated using either the incidence of macrosomia observed in our population , or the incidence of macrosomia observed theoretically in the absence of treatment ( 22 % in literature ) . RESULTS Macrosomia was diagnosed in 49 neonates ( 14 % ) . The " practical " test was significantly more sensitive than the reference test ( respectively 46.9 % versus 16.3 % , p=0.0001 in the first case , and 54.3 % versus 20.1 % , p=0.0001 in the second case ) . The " reference " test was significantly more specific than the " practical " test ( respectively 80 % versus 68.2 % , p=0.0001 in the first case , and 80.6 % versus 70 % , p=0.0001 in the second case ) . CONCLUSION Our study shows that the simplified " practical " test is more sensitive than the " reference " test currently used in France in screening women at risk of macrosomia OBJECTIVE Our aim was to study whether universal screening of all pregnant women by Oral Glucose Challenge Test ( OGCT ) would identify a higher number of women with Gestational Diabetes ( GDM ) than risk factor based screening . STUDY DESIGN A 50 g OGCT test was performed prospect ively in 532 unselected women at 26 - 28 weeks of gestation . The 1-h venous plasma glucose concentration of > 7.3 mmol/l was considered as a positive screening result . Patients with a positive OGCT underwent a 75 g 2-h OGTT , which was used as the actual diagnostic test for GDM . When two or all three of the glucose concentrations in OGTT ( measured at fasting state and 1 and 2 h after the 75 g glucose load ) were above the 97.5th percentile the patient was considered as having GDM . In addition , women with risk factors for GDM also underwent a 75 g OGTT regardless of the result of the OGCT . RESULTS A positive 50 g OGCT was obtained in 123 ( 23 % ) of the women . In 15 ( 12 % ) of these , a diagnosis of GDM was established by the subsequent OGTT . Out of the 409 remaining women with a normal OGCT , 148 ( 36 % ) had risk factors for GDM . An OGTT performed in these patients identified 4 additional women with a GDM . Seventy-nine percent of GDM was thus found with 50 g OGCT without regarding risk factors . Forty-seven percent of the women with GDM would have been missed in screening by risk factors only . CONCLUSIONS In our population 50 g OGCT appears to identify a higher number of GDM than risk factor based screening . Combined with risk factor screening a few more cases of GDM would be found OBJECTIVES To test the validity of a 75-g , 2-h oral glucose tolerance test ( OGTT ) for diagnosing gestational diabetes mellitus ( GDM ) using the criteria and reference values suggested by the American Diabetes Association for the 100-g , 3-h OGTT . METHODS The results of a 75-g , 2-h OGTT were compared with those of a 100-g , 3-h OGTT in 42 pregnant women . The women 's mean+/-S.D. age and gestational age were 33.6+/-5.4 years and 28.2+/-4.2 weeks , respectively . Each subject was r and omly scheduled within 1 week for both the 75-g and 100-g OGTTs . RESULTS The mean plasma glucose concentrations at 1 , 2 , and 3 h during the 100-g OGTT were significantly higher than those during the 75-g OGTT . Using the Carpenter and Coustan criteria , the prevalence of GDM was 21.4 % when using the 100-g , 3-h OGTT , whereas it was found to be at only 7.1 % when using the 75-g , 2-h OGTT . CONCLUSIONS Plasma glucose responses during the 75-g OGTT were found to be lower than those during the 100-g OGTT . When using the same diagnostic criteria , the prevalence of GDM was also found lower using the 75-g glucose load . It would therefore not be appropriate to use the 75-g OGTT for diagnosing GDM using the criteria and reference values of the 100-g OGTT . To give a comparable prevalence of GDM , the threshold of abnormal plasma glucose levels of the 75-g OGTT would need to be lower than that of the 100-g OGTT INTRODUCTION Early diagnosis of gestational diabetes mellitus ( GDM ) is a prerequisite to reducing fetal and neonatal complications of GDM . OBJECTIVES ( a ) To ascertain the prevalence of GDM in a Sri Lankan pregnant population . Using the 75 g oral glucose tolerance test ( GTT ) and WHO criteria . ( b ) To establish the predictive value of a 50 g glucose challenge test ( GCT ) compared to the GTT ( c ) To compare the outcome of pregnancy in GDM with ' non-diabetic pregnancy ' ( NDP ) STUDY DESIGN : Prospect i ve study on a cohort of pregnant women attending antenatal clinics . SETTING Sri Jayawardenepura General Hospital ( SJGH ) RESULTS : Of the 721 patients , 131 ( 18 % ) had a positive GCT . 40 ( 5.5 % ) patients had GDM . If a one-hour GCT of 7.8 mmol/l was considered suspicious of GDM the sensitivity of the glucose challenge test was 63 % and the specificity 84 % . Statistically significant differences in the prevalence was found when the women were > 35 years [ Relative risk ( RR ) = 3.87 ( 95 % CI-2.06 to 7.27 ) ] or the body mass index > or = 25 . ( RR = 2.45 ( 95 CI-1.30 to 4.61 ) Presence or absence of high parity , family history of diabetes or recurrent abortions had no significant impact on the prevalence of GDM . Mean birth weight was higher ( p < 0.05 ) in GDM ( 3615 SD 103 ) than in NDP ( 2898 SD 143.6 ) . The likelihood of having a caesarean section was higher ( p < 0.01 , Relative risk ( RR ) 2.50 , 95 % CI 1.56 - 3.95 ) in GDM when compared to NDP . A higher incidence of hydramnios ( p < 0.01 RR 3.41 95 % CI 1.44 - 8.05 ) was recorded in GDM when compared to NDP . CONCLUSION The prevalence of GDM in the antenatal clinics at SJGH is 5.5 % . Traditional risk factors did not predict GDM . GDM is associated with a higher risk of caesarean section , hydramnios and macrosomia . Hence screening for GDM should be performed in all pregnant women at 24 to 28 weeks of pregnancy using a GCT OBJECTIVE This study was performed to prospect ively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators . STUDY DESIGN In a prospect i ve multicenter study with 5235 consecutive pregnant women , diagnostic testing with a 2-hour 75-g oral glucose tolerance test was routinely performed in women with risk indicators and offered to women without risk indicators as part of the study . RESULTS Forty-four percent of the women underwent testing , 43 % declined participation , 6 % did not speak Danish , and 7 % could not be contacted . By extrapolation of the results from tested women to the whole group in question , a 2.4 % prevalence of gestational diabetes mellitus was calculated . Sensitivity and specificity of the model was 80.6 ( 73.7 - 87.6 ) and 64.8 ( 63.5 - 66.1 ) , respectively ( 95 % CIs ) . CONCLUSION Under ideal conditions , sensitivity of the model was comparable with universal screening by fasting glucose or a 1-hour 50-g glucose challenge test . Both screening and diagnostic testing could be avoided in two thirds of all pregnant women OBJECTIVE This study tested the hypothesis that a st and ardized dose of jelly beans could be used as an alternative sugar source to the 50-g glucose beverage to screen for gestational diabetes mellitus . STUDY DESIGN One hundred sixty pregnant women at 24 to 28 weeks ' gestation were recruited for a prospect i ve study to compare 2 sugar sources for serum glucose response , side effects , preference , and ability to detect gestational diabetes mellitus . Patients were r and omly assigned to consume 50-g glucose beverage or 28 jelly beans ( 50 g simple carbohydrate ) . Serum glucose values were determined 1 hour later . The test was later repeated with the other sugar source . Finally , a 100-g 3-hour oral glucose tolerance test was performed . Participants completed a question naire recording subjective outcome variables . American Diabetes Association criteria were used to interpret all test results . RESULTS Among 136 participants completing the study no significant differences were found between 1-hour serum glucose values ( 116.5 + /- 27 mg/dL with 50-g glucose beverage , 116.9 + /- 23.6 mg/dL with jelly beans ; P = .84 ) , frequency of discrepant results ( P = .47 ) , sensitivity , specificity , or predictive value . Jelly beans yielded fewer side effects ( 38 % with 50-g glucose beverage , 20 % with jelly beans ; P < .001 ) and were preferred by 76 % of participants ( P < .001 ) . Five cases ( 3.7 % incidence ) of gestational diabetes mellitus were diagnosed , 3 with 50-g glucose beverage alone , 1 with jelly beans alone , and 1 with both sugar sources . CONCLUSIONS Jelly beans may be used as an alternative to the 50-g glucose beverage as a sugar source for gestational diabetes mellitus screening . The 2 sources provoke similar serum glucose responses . Patients report fewer side effects after a jelly bean challenge than after a 50-g glucose beverage challenge OBJECTIVE To evaluate tests used for screening and confirmation of gestational diabetes mellitus ( GDM ) in Sri Lanka . METHODS FIELD BASED Consecutive pregnant women in Homagama DDHS area ( n = 853 ) , were assessed for risk factors and subjected to r and om and postpr and ial urinary Benedict 's and Dipstick tests , fasting and 2 hour post 75 g glucose capillary blood glucose ( FBG and 2hBG ) which were vali date d against 75 g oral glucose tolerance test ( OGTT ) performed at 24 - 28 weeks ( WHO criteria ) . HOSPITAL BASED Retrospective analysis of consecutive high-risk women ( n = 999 ) and prospect i ve study of r and omly selected GDM women ( n = 66 ) to assess predictive value of the OGTT . RESULTS FIELD BASED Sensitivity and specificity respectively of r and om urine Benedict 's , 10 % , 99.2 % ; postpr and ial urine Benedict 's , 52.2 % , 94.5 % ; postpr and ial urine Dipstick , 68.7 % , 90 % ; capillary FBG threshold 4.1 mmol/l , 62.6 % , 73 % ; capillary 2hBG threshold 7.2 mmol/l , 98.5 % , 95.2 % ; risk factors , 93.1 % , 22.2 % . HOSPITAL BASED OGTT-11.6 % lag curves , 16.3 % abnormal , FPG accuracy at 4.7mmol/l ; predictive value of 2 hPG > or = 8.9 mmol/l for insulin treatment-sensitivity 97.2 % , specificity 71.4 % . CONCLUSIONS Current practice of r and om urine testing in community screening for gestational diabetes is unreliable , and glucose specific postpr and ial urine test improves sensitivity . FPG is unsuitable for screening , the 2 hour post 75 g blood glucose at a threshold of > 7.2 mmol/l is sensitive and specific . In laboratory confirmation using 75 g OGTT the fasting plasma glucose has low predictive value , 2 hour test performed alone is liable to false positives and 2 hour glucose > 8.9 mmol/l following a peak at 1 hour suggests the need for insulin treatment AIM This study aim ed to investigate the cut-off value of the glucose challenge test in an Iranian population . MATERIAL S AND METHODS A total of 1804 consecutive native Iranian women who underwent a glucose challenge test were prospect ively investigated . The test was performed between 24 and 28 weeks of gestation ; each subject received a 50-g oral glucose load regardless of her fasting or fed state ; the 1-h venous plasma glucose level was then determined . Women exceeding 130 mg/dl received the diagnostic 100-g , 3-h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus . RESULTS The prevalence of the glucose challenge test for the whole cohort was 7.2 % . The receiver-operator characteristic curve identified a glucose challenge test finding above 135 mg/dl as the cut-off value for detecting gestational diabetes mellitus , which showed a sensitivity and specificity of 95 % and 80 % , respectively . CONCLUSION Our results suggest that the cut-off value of a 50-g glucose challenge test is 135 mg/dl to identify pregnancies with gestational diabetes mellitus in an Iranian population OBJECTIVES To evaluate the applicability of the 50-g glucose challenge test as a screening test for gestational diabetes mellitus in relation to pregnancy outcomes . METHODS A prospect i ve study was conducted on 818 Saudi pregnant females who were r and omly recruited from the Antenatal Clinics at King Abdulaziz University Hospital and New Jeddah Clinic Hospital , Jeddah . All females underwent a 50-g glucose challenge test between 24 - 28 weeks gestation . A result for 50-g glucose challenge test was considered positive at > 7.2 mmol/L and the female was asked to undergo a 100-g oral glucose tolerance test . The diagnosis of gestational diabetes mellitus was carried out according to the National Diabetes Data Group criteria . RESULTS A total of 289 females exhibited plasma glucose level > 7.2 mmol/L following the 50-g glucose challenge test . Of the 289 females enrolled for the 100-g oral glucose tolerance test , 102 were diagnosed to have gestational diabetes mellitus ( positive oral glucose tolerance test ) and 187 were considered oral glucose tolerance test negative according to the National Diabetes Data Group diagnostic criteria . This gave a prevalence of gestational diabetes mellitus of 12.5 % . Gestational diabetes mellitus females were significantly older in age , heavier in weight , with higher gravidity , greater percentage of operative deliveries and still-births , and heavier fetal birth weight as compared with the non-gestational diabetes mellitus group ( P<0.05 in each case ) . The maximum sensitivity and specificity of the 50-g glucose challenge test were found to be at plasma glucose value of 7.8 mmol/L post the 50 g glucose load . The sensitivity and specificity of this value was 88 % and 84 % , with a positive predictive value of 82 % . To determine whether the values of plasma glucose after a 50-g glucose load were detecting abnormalities similar to those detected according to that of oral glucose tolerance test ; the values obtained one-hour post the 50-g glucose challenge test were compared with zero- , one- , 2- and 3-hour values and also the area under the curve in the 100-g oral glucose tolerance test . Plasma glucose post the 50-g glucose challenge test showed marked correlation with oral glucose tolerance test results . This was mostly occurring at the one- and 2-hour oral glucose tolerance test values and was stronger in the gestational diabetes mellitus group and in both the gestational diabetes mellitus plus negative oral glucose tolerance test combined , than in the negative oral glucose tolerance test group on its own . CONCLUSION It is concluded that plasma glucose level measured one-hour post a 50-g glucose challenge test at 24 - 28 weeks of gestation with a cut-off value of 7.8 mmol/L is a reliable screening test for gestational diabetes mellitus in the local population studied . This test offers the best combination of ease and economy of use and reproducibility in screening for gestational diabetes mellitus OBJECTIVE : We sought to describe the predictive value for gestational diabetes mellitus ( GDM ) using different glucose challenge test thresholds in Mexican-American women . METHODS : A prospect i ve population -based study of 6,857 gravid women , who were tested with a 50-g glucose challenge test at 24–28 weeks of gestation , was performed . A screening value of 130 mg/dL or greater was followed by a 3-hour , 100-g oral glucose tolerance test . Gestational diabetes mellitus was diagnosed by 2 or more abnormal values using the Carpenter and Coustan criteria . For purpose of analysis , GDM diagnosis was categorized with glucose challenge test values in 10-mg/dL increments . A comparison between Carpenter-Coustan and the National Diabetic Data Group criteria for GDM diagnosis was performed for each glucose challenge test threshold category . Sensitivity and specificity for GDM diagnosis were further calculated for different glucose challenge test thresholds ( 130 , 135 , and 140 mg/dL ) . RESULTS : Overall , GDM was diagnosed in 469 of 6,857 ( 6.8 % ) women , and one abnormal oral glucose tolerance test value was tested in 351 of 6,857 women ( 5.1 % ) . Normal glucose challenge test results ( threshold less than 130 mg/dL ) were obtained in 4,316 of 6,857 women . An elevated glucose challenge test value increases the risk of GDM , but even in high glucose challenge test thresholds ( more than 180 mg/dL ) , the predictive value for GDM was only 50 % . The sensitivity and specificity for GDM diagnosis using 3 different glucose challenge test thresholds were as follows : threshold 130 mg/dL or more : 97 % and 63 % ; threshold 135 mg/dL or more : 91 % and 73 % ; and threshold 140 mg/dL or more : 85 % and 78 % , respectively . CONCLUSION : Data suggests that an elevated glucose challenge test level can not be used as a single diagnostic tool for GDM even in high test thresholds . A threshold of 130 mg/dL may be recommended as a screening threshold for GDM in Mexican-American women . LEVEL OF EVIDENCE : We evaluated variations in glucose measurements and the reproducibility of glucose tolerance classification in a high-risk screening setting in general practice . Screening for diabetes was performed in persons aged 40 - 69 years . Based on capillary fasting ( FBG ) and 2-h blood glucose ( 2 hBG ) individuals with impaired fasting glycaemia ( IFG ) , impaired glucose tolerance ( IGT ) and diabetes had a second test done after 14 days . Intra-individual coefficients of variation ( CV ) were estimated in each glucose tolerance class using the approximation CV(2)(x)=var(ln(x ) ) . Bl and -Altman plots with limits of agreement were made . In the total population , the CV(intra ) was 7.9 % and 13.8 % for FBG and 2 hBG , respectively . Limits of agreement ranged from -1.15 to 1.67 mmol/l for FBG and from - 2.62 to 3.27 mmol/l for 2 hBG . One individual with IFG and 22.5 % with IGT had diabetes at the second test , 76.1 % with diabetes had this diagnosis confirmed , and about 30 % with IFG and IGT had normal glucose tolerance at the second test . The expected values of repeated capillary blood glucose measurements were about+/-1 and + /-3 mmol/l for FBG and 2 hBG , respectively . Yet , 70 % of high-risk prediabetic individuals were persistently classified with abnormal glucose regulation ; diabetes was confirmed in 76 % of the cases You are back where we put you in the previous article1 on diagnostic tests in this series on how to use the medical literature : in the library study ing an article that will guide you in interpreting ventilation-perfusion ( V/Q ) lung scans . Using the criteria in Table 1 , you have decided that the Prospect i ve Investigation of Pulmonary Diagnosis ( PIOPED ) study 2 will provide you with valid information . Just then , another AIM Currently , there is no international consensus for gestational diabetes mellitus ( GDM ) diagnosis . This is a report of our experience of GDM screening according to the 1996 French guidelines . METHODS For 5 years , all pregnant women followed at our hospital ( n=11,545 ) were prospect ively screened for GDM between weeks 24 and 28 of pregnancy with a two-step strategy : the O'Sullivan test ( OS ) with a threshold at 130 mg/dL , followed by a 100-g OGTT if positive . GDM was diagnosed according to Carpenter and Coustan criteria . RESULTS Prevalence of GDM was 4.26 % [ 344/1451 of patients with an OS of 130 - 199 mg/dL ( 12.1 % ) ; and 148 patients with an OS greater than 200 mg/dL ] . The false-positive rate for the OS was 76.8 % . Compared with 140 mg/dL , a threshold of 130 mg/dL caused 401 additional negative OGTTs in 90 % of cases . In 80.7 % GDM patients , fasting glucose was less than 95 mg/dL. The time lag between OS and OGTT was 3 weeks ( 1 - 84 days ) . Risk factors associated with GDM were maternal age , preconception overweight and obesity , parity , personal history of GDM or macrosomia , and familial history of obesity ( P<0.05 ) , but not diabetes . Also , 20 % of GDM patients had no risk factors , whereas they were present in 75 % of patients without GDM . CONCLUSION In our population , a two-step screening strategy for GDM was neither relevant nor efficient . It could be simplified with a single-step definitive screening strategy using a 75-g OGTT , as used in the HAPO study , and as recommended by the IADPSG and the recent French Expert Consensus . At present , there are still no evidence -based arguments to help in deciding between selective or universal screening for GDM Objective To test the hypothesis that glucose abnormality , as shown by glucose tolerance test ( GTT ) periodicity , is not affected by different glucose loads , allowing for the identification of gestational diabetes mellitus ( GDM ) under varying glucose challenges . Methods Eighty subjects were tested by multiple GTTs 1 week apart . Each woman served as her own control , undergoing a st and ard 3-hour , 100-g GTT ; then , half of the subject group r and omly underwent a 50-g and the other half a 75-g , 2-hour GTT . Subjects were classified using National Diabetes Data Group thresholds for the 100-g GTT . Those with two or more abnormal values were classified as gestational diabetic ( GDM group ) ; the rest of the women were considered to be nondiabetic . The projected time for the GTT to revert to fasting value , GTT periodicity , was then deter-mined for each glucose load in the GDM and nondiabetic groups . Results All glucose values for the nondiabetic group were significantly lower at 1 and 2 hours than those for the GDM group , regardless of the glucose load ( P < .04 ) . There was a statistically significant difference within the GDM and non-diabetic groups between glucose values of the 100- and 50-g GTTs at 1 hour ( P < .02 ) and between all loads at 2 hours ( P < .04 ) . The GTT periodicity for the 3-hour , 100-g test was significantly longer for patients with GDM , as shown previously ( 5.6 ± 1.9 versus 3.2 ± 1.7 hours , P < .0001 ) . In addition , similar values were found for nondiabetic and GDM subjects for the 75-g ( 5.1 ± 2 versus 3.6 ± 1.8 hours , P < .04 ) , but not the 50-g load ( 2.2 ± .6 versus 1.34 ± .8 hours , P < .01 ) . Conclusion Glucose tolerance test periodicity will identify subjects with GDM regardless of GTT load because the physiologic disturbance of glucose level measured by this time period remains comparably longer than in normal subjects . We speculate that the relatively shorter cycle of the 50-g load may reflect an insufficient challenge to pancreatic function AIMS To clarify risk factors predictive of glucose intolerance in later pregnancy . METHODS We prospect ively studied 509 pregnant women who visited the obstetrics clinic in Tokyo prior to week 13 of gestation , between September 2008 and January 2010 . Biochemical parameters were measured in fasting plasma sample s collected at week 8.0 ± 2.0 of gestation . A 50 g glucose challenge test ( GCT ) was performed between weeks 26 and 29 : plasma glucose levels ≥ 7.8 mmol/l 1h after ingestion indicated a positive GCT . Logistic regression was performed , adjusting for relevant covariates . RESULTS We identified 114 patients with positive GCTs , including 8 with gestational diabetes mellitus ( GDM ) . After correcting for baseline body mass index , only the homeostasis model assessment of insulin resistance value remained a significant predictor of GCT positivity ( OR 2.07 ; 1.21 - 3.55 ) . We identified threshold values of fasting plasma glucose ( FPG ) ≥ 3.66 mmol/l and fasting plasma insulin ( FPI ) ≥ 36.69 pmol/l as indicative of a higher risk of positive GCT ( OR 2.38 ; 1.49 - 3.80 ) . CONCLUSIONS First trimester FPI levels improve the predictive ability of FPG level on subsequent GCT positivity This study compared the results of a 75-g , 3-hour oral glucose tolerance test with those of a traditional 100-g oral glucose tolerance test . Thirty-two pregnant women participated in the study . Each patient served as her own control , undergoing both a 100- and a 75-g oral glucose tolerance test within 1 week . Despite a strong positive correlation between the results of the two tests , the 1- , 2- , and 3-hour glucose values of the 100-g glucose load were significantly higher than the comparable values of the 75-g oral glucose tolerance test . Sixteen of 32 women were diagnosed as having gestational diabetes mellitus using the National Diabetes Data Group criteria and the 100-g oral glucose tolerance test , whereas only 6 of these 16 women would have been identified with the 75-g oral glucose tolerance test . If data from one test are to be compared with the other , new thresholds of glucose abnormality need to be developed Please cite this paper as : Meltzer S , Snyder J , Penrod J , Nudi M , Morin L. Gestational diabetes mellitus screening and diagnosis : a prospect i ve r and omised controlled trial comparing costs of one‐step and two‐step methods . BJOG 2010;117:407–415 |
11,126 | 26,174,117 | Depression and fatigue are highly prevalent , and the dyads , patient and partner , are at higher risk for distress symptoms .
The efforts of individuals to cope with metastatic PC appear influenced by adaptative skills and specific types of family support .
In metastatic PC patients , needs change during the course of the disease .
Social support plays a major role in maintaining or disrupting QoL and in the efficacy of psychosocial treatments . | Patients with metastatic prostate cancer ( PC ) live longer than patients with metastatic tumours of other sites .
Consequently , their social network can influence their quality of life ( QoL ) during a remarkable life span .
The aim of this article is to present the findings of a systematic review of the studies that focused on social network supporting the quality of life of these patients .
Psychological and relational problems predominate in the hormone-sensitive stage and are increasingly replaced by physical symptoms , social and spiritual needs in the later stages . | The objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer . Semi-structured qualitative interviews were conducted with 50 women at two time points ( baseline and 6 months later ) . The interviews examined emotions , experiences , attitudes to sexual and continence issues and treatment decision making . As part of a larger prospect i ve observational study , demographic data and scores for depression and anxiety were collected . Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months . In contrast , the 39 women in the non-distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves , appraisal of coping strategies and re appraisal of the situation . A surprise finding was the high level of resilience displayed by majority of these women . Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples Prostatic carcinoma and its treatment have been associated with adverse effects on health-related quality of life ( HRQoL ) . Individual differences in appraisal and coping have been suggested to mediate these HRQoL outcomes . A r and omized trial of 65 men with non-localized prostate cancer compared several treatments and tested associations between appraisal , coping , and HRQoL. These patients , and 16 community volunteers matched for age and general health , undertook psychosocial assessment s before treatment and after 6 months of treatment . Compared with baseline assessment s , men on hormonal treatments reported impaired sexual function . Groups did not differ on emotional distress , existential satisfaction , subjective cognitive function , physical symptoms , or social and role functioning . For individuals , hormonal treatments were more frequently associated with decreased sexual , social and role functioning , but were also associated with improved physical symptoms . In hierarchical regression analysis , HRQoL was lower for men who had more comorbid illnesses , a history of neurological dysfunction , higher threat appraisal s , or higher use of coping strategies at baseline . These results showed that pharmacological hormonal ablation for prostate cancer can improve or decrease HRQoL in different domains . HRQoL in men with prostate cancer was associated more strongly with appraisal and coping than with medical variables PURPOSE We prospect ively examined the development of depressive symptoms and fatigue among men with locally advanced prostate cancer receiving hormone therapy . METHODS Fifty-two men with advanced or recurrent prostate cancer were r and omly assigned to receive either parenteral leuprolide or oral bicalutamide . Patients completed the Beck Depression Inventory ( BDI ) and Fatigue Severity Scale ( FSS ) at pretreatment baseline , 6 months , and 12 months . RESULTS Rates of at least mild depression ranged from 10.4 to 16.3 % over the 12 months and were not significantly different at each time point . Mean change in BDI scores from baseline to 6 months for the entire sample was 0.91 ( SE = 0.73 ) , and from baseline to 12 months was 0.35 ( SE = 0.67 ) . Mean FSS scores increased significantly from baseline ( M = 24.43 , SD = 11.75 ) to 6 months ( M = 27.93 , SD = 13.52 ) and remained steady at 12 months ( M = 27.80 , SD = 14.44 ) . There were no significant differences in depression between the two types of hormone therapy . CONCLUSION Hormone therapy does not appear to cause clinical ly significant changes in depression among men with locally advanced prostate cancer . However , fatigue increased significantly over the study period This study was undertaken to evaluate the quality of life ( QoL ) of previously untreated patients with M1 prostate cancer before and during and rogen-suppressive treatment . Assessment of QoL was included as an optimal component of EORTC protocol 30853 , a phase III trial comparing LH-RH ( luteinising hormone-releasing hormone ) analogue combined with a non-steroidal anti- and rogen versus orchiectomy in patients with M1 prostate cancer . At pretreatment and during the follow-up period , patients were asked to complete a question naire assessing their physical and psychosocial functioning , and their symptom levels . Physicians rated the patients ' performance status , pain , urological symptoms and erectile function . Due to its optional nature , only a minority of the patients in the trial were recruited for the QoL investigation . 63 patients completed a pretreatment question naire , of whom 49 completed a second question naire at least once during the initial 15 month follow-up period . While statistically significant correlations were observed between patients ' and physicians ' ratings of physical functioning and pain , these were of only a moderate magnitude ( r = 0.43 and 0.30 , respectively ) . No significant association was observed between physicians ' and patients ' ratings of micturation problems or of erectile function . Before treatment , fatigue , pain and decreased social role and sexual functioning were the problems most frequently reported by patients . With an average of approximately 1 year follow-up , statistically significant improvements were observed in patients ' self-reported urological symptoms and metastatic pain . No significant changes were noted for the other QoL domains assessed . The results of this study confirm earlier findings that physicians ' ratings may not reflect accurately the functional health and symptom experience of their patients . Patient-based QoL question naires offer the most direct means of evaluating the subjective morbidity associated with prostate cancer and its treatment . To increase participation and compliance rates in future studies , it is recommended that QoL assessment be made m and atory in those clinical trials in which QoL is considered to be an important study endpoint OBJECTIVES The quality of life ( QoL ) of 44 men with HRPC and 37 partners ( primary caregivers , most residing with the patient ) was assessed in a multicenter Phase II trial of docetaxel , estramustine and low dose hydrocortisone ( CALGB 9780 ) . A secondary objective was to test the feasibility of assessing partners ' QoL in a cooperative group setting . PATIENTS AND METHODS Patients and partners were separately interviewed by telephone at baseline , two , four and six months by a single trained research interviewer . Patients ' QoL was measured by the FACT-P , Mental Health Inventory-17 ( MHI-17 ) , Brief Pain Inventory ( BPI ) , a two-day log of pain medications , and the OARS for co-morbid conditions . Partners ' QoL was measured by the MHI-17 , Caregiver Burden Interview , and co-morbid conditions . RESULTS The QoL study refusal rates were low for patients ( 4 % ) and partners ( 3 % ) . Although patients tended to experience greater treatment side effects in the first two months ( FACT Physical Well-Being item , P = 0.057 ) , their cancer-specific emotions ( e.g. , worrying about worsening health ) significantly improved at two and four months ( FACT-Emotional Well-Being , P = 0.003 , P = 0.03 , respectively ) , as did their prostate cancer-specific physical problems ( e.g. , urination , pain ) , at two and four months ( FACT-P , P = 0.001 , P = 0.005 , respectively ) . Partners ' anxiety significantly decreased over time ( MHI , P < 0.05 ) . Patients ' quality of life at two months was significantly related to their clinical response ( FACT-P total and prostate cancer-specific problems , P < 0.05 ) , and their clinical response was significantly related to a decrease in their partners ' anxiety at two months ( MHI , P < 0.05 ) . CONCLUSIONS Despite feeling worse from side effects , patients ' prostate cancer-specific problems and emotional state significantly improved in the first four months of treatment . With treatment significantly affecting both patients ' and partners ' lives . and the successful assessment of partners ' QoL , QoL of both patients and partners could be used as important endpoints in selected clinical trials OBJECTIVE To assess psychosocial distress in patients with early ( localised ) and advanced ( metastatic ) prostate cancer ( PCA ) at diagnosis ( Time 1 ) and 12 months later ( Time 2 ) , and identify psychosocial factors predictive of later distress . DESIGN , PARTICIPANTS AND SETTING Observational , prospect i ve study of 367 men with early ( 211 ) or advanced ( 156 ) PCA recruited as consecutive attendees at clinics at seven public hospitals and practice s in metropolitan Melbourne between 1 April 2001 and 30 December 2005 . Both groups completed question naires at Time 1 and Time 2 . MAIN OUTCOME MEASURES Health-related quality of life as assessed by the Short Form 36-item Health Survey ; psychological distress , including depression and anxiety as assessed by the Brief Symptom Inventory ; and coping patterns as assessed by the Mini-Mental Adjustment to Cancer scale . RESULTS Over the 12 months , both the early and advanced PCA group showed reduced vitality and increased depression and anxiety ; this effect was greater in the advanced PCA group . Mental health , social functioning and role-emotional functioning also deteriorated in the advanced group . Predictors of depression at Time 2 for the early PCA group were depression , vitality and a fatalistic coping pattern at Time 1 ; anxiety at Time 2 was predicted by anxiety and vitality at Time 1 . In the advanced PCA group , depression at Time 2 was predicted by depression and mental health at Time 1 ; anxiety at Time 2 was predicted by anxiety , mental health , cognitive avoidance and lower anxious preoccupation at Time 1 . CONCLUSIONS Men with early PCA experience decreasing vitality and increasing psychological distress over the 12 months following diagnosis ; this trend is accelerated after diagnosis with advanced PCA . A fatalistic coping pattern at diagnosis of early PCA predicts later depression while cognitive avoidance and lower anxious preoccupation at diagnosis of advanced PCA predict later anxiety AIMS The prevalence of anxiety and depression in patients with advanced cancer has been reported to be on average 25 % and to significantly affect patients ' quality of life . Despite high prevalence rates , these disorders remain underdiagnosed and undertreated . The purpose of our study was to examine the self-report rates of anxiety and depression with the Edmonton Symptom Assessment System ( ESAS ) and to assess the predictive factors for these reports in cancer patients with metastatic disease . MATERIAL S AND METHODS Consecutive patients who attended the Rapid Response Radiotherapy Program ( RRRP ) completed the ESAS as well as baseline demographic information . Ordinal logistic regression analysis was used to determine factors that significantly predicted anxiety and /or depression . Pearson χ(2 ) was used to test goodness-of-fit for categorical variables and established whether or not an observed frequency distribution differed from a predicted frequency distribution . A univariate analysis was conducted first and those variables with a P value<0.100 were included in a multivariate analysis . A score test was used to test the proportional odds assumption . RESULTS In total , 1439 patients seen in the RRRP between January 1999 and October 2009 completed ESAS question naires . Fifty-five per cent of patients reported at least mild symptoms of depression and 65 % reported at least mild anxiety . In the univariate analysis , patients who were female , who had a lower performance status score , or primary lung cancer were more likely to report depressed and anxious feelings . Primary prostate cancer patients were significantly less likely to report depression and anxiety . Patients referred for spinal cord compression were significantly less depressed . The multivariate models showed that younger patients were significantly more anxious than older patients and females reported more anxiety than males . Patients who reported higher feelings of nausea , tiredness , drowsiness , dyspnoea , and worse appetite and overall well-being on the ESAS tool were more likely to report feelings of depression . Patients who reported higher nausea , drowsiness , dyspnoea and worse overall well-being more often reported higher feelings of anxiety . CONCLUSION The self-report rates of anxiety and depression were consistent with published prevalence rates . However , the explained variance based on factors included in the model remains low . Additional predictive factors should be examined in future studies in this population . The ESAS tool seems to be an efficient screening tool for anxiety and depression ; however , future studies should examine its correlative properties with other known screening tools in the advanced cancer population . A prospect i ve study should be conducted to assess the severity cut-off point in which the ESAS scores most frequently lead to a further diagnosis of an anxiety or depressive disorder in the advance cancer population PURPOSE To examine prospect ively the influence of social networks on health-related quality of life ( HRQoL ) among breast cancer survivors . METHODS Social networks and HRQoL were assessed among women free of breast cancer in the Nurses ' Health Study ( NHS ) . Women who developed breast cancer over a 4-year follow-up ( n=708 ) completed detailed questions related to treatment together with an assessment of general and cancer-specific HRQoL. RESULTS On average , socially isolated women were more adversely affected by breast cancer -- their role function was lower by 14 points , vitality lower by 7 points , and physical function lower by 6 points compared to the most socially integrated women . CONCLUSION Prediagnosis level of social integration is an important factor in future HRQoL among breast cancer survivors , and appears to explain more of the variance in HRQoL than treatment or tumor characteristics . Rehabilitation programs should incorporate interventions that address the availability of adequate social support among breast cancer survivors |
11,127 | 20,878,529 | Conclusion The systemic inflammatory response predicted poor survival in patients with renal cell carcinoma | Purpose To summarize the global predicting role of systemic inflammatory response for survival in renal cell carcinoma . | OBJECTIVES To determine whether preoperative laboratory values are independently associated with death from clinical ly confined clear cell renal cell carcinoma ( RCC ) after radical nephrectomy . METHODS We identified 1707 patients with clinical ly confined ( pNx/pN0 , pM0 ) , unilateral , sporadic clear cell RCC treated with radical nephrectomy between 1970 and 2002 . Associations of abnormal preoperative laboratory values including hypercalcemia , anemia , elevated erythrocyte sedimentation rate ( ESR ) , and elevated alkaline phosphatase with death from RCC were evaluated using Cox proportional hazards regression models , both univariately and multivariately by adjusting for known prognostic features of the 2002 primary tumor classification , tumor size , nuclear grade , and coagulative tumor necrosis . RESULTS At last follow-up , 1009 patients had died , including 425 who died from RCC at a median of 3.0 years after surgery ( range , 0 to 26 years ) . Even after adjusting for known prognostic features , 9 % of patients with preoperative hypercalcemia exhibited significantly increased likelihood of dying from RCC compared with patients with normal or lower levels of serum calcium ( relative ration [ RR ] 1.64 ; P = 0.002 ) . Similarly , preoperative anemia ( 35 % of patients ; RR 1.27 ; P = 0.026 ) and elevated ESR ( 44 % of patients ; RR 1.66 ; P = 0.003 ) portended an increased risk of death from RCC even after multivariate adjustment . CONCLUSIONS Abnormal preoperative laboratory values including hypercalcemia , anemia , and elevated ESR are independently associated with increased risk of cancer-specific death from clinical ly confined clear cell RCC . Consideration of these variables in future models may improve prognostic accuracy . We believe these factors should be routinely assessed and included in prospect i ve studies of outcome in RCC patients |
11,128 | 21,537,143 | Overall , a melanoma-specific immune response predicted longer overall survival , although no evidence was found that vaccine therapy provides better overall disease control or overall survival compared with other treatments | Clinical trials of melanoma vaccines have yielded inconclusive data on whether a positive melanoma-specific immune response predicts treatment benefit .
The objective of this study was to evaluate the effect of different melanoma vaccine strategies and the association between immunologic response and survival . | We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells ( DCs ) with autologous tumor-mRNA . Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens , including unique patient-specific antigens . The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine , and the ability of the DCs to elicit T-cell responses in melanoma patients . Further , we compared intradermal ( i.d . ) and intranodal ( i.n . ) vaccine administration . Twenty-two patients with advanced malignant melanoma were included , each receiving four weekly vaccines . Monocyte-derived DCs were transfected with tumor-mRNA by electroporation , matured and cryopreserved . We obtained successful vaccine production for all patients elected . No serious adverse effects were observed . A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays ( T-cell proliferation/interferon-γ ELISPOT ) and in 8/18 patients evaluable by delayed-type hypersensitivity ( DTH ) reaction . The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally . We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe , and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA . The response rates do not suggest an advantage in applying i.n . vaccination Adoptive immunotherapy with anti-CD3-exp and ed lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors . This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-exp and ed tumor vaccine draining lymph node lymphocytes ( TVDLN ) in patients with metastatic melanoma and renal cell cancer ( RCC ) . To facilitate the generation of tumor-specific lymphocytes in the TVDLN , autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7 , a modification that has the potential to enhance the immunogenicity of the tumor cells . After vaccination with gene-modified tumor cells , patients ' lymph nodes were harvested ; TVDLN lymphocytes were activated and exp and ed ex vivo with anti-CD3 and interleukin-2 ( IL-2 ) , and adoptively transferred to patients in combination with systemic IL-2 . Twenty patients , nine with melanoma and 11 with RCC were treated . Tumor was harvested successfully in all 20 patients . Ex vivo gene transfer was performed using lipofection with a lipid : DNA plasmid complex containing the genes for HLA-B7 and & bgr;2-microglobulin . The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53 % ( range 0.3%–12.1 % ) . Lymph nodes were harvested from all 20 patients with a mean of 53 × 107 and 60 × 107 cells obtained from the gene-modified and unmodified tumor vaccine sites , respectively . Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines . No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes . Typical IL-2-related toxicities were observed in all patients . No objective tumor regressions were observed . MHC class I restricted , tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients PURPOSE To assess the antitumor activity of vitespen ( autologous , tumor- derived heat shock protein gp96 peptide complexes ) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician 's choice . PATIENTS AND METHODS Patients ( N = 322 ) were r and omly assigned 2:1 to receive vitespen or physician 's choice ( PC ) of a treatment containing one or more of the following : dacarbazine , temozolomide , interleukin-2 , or complete tumor resection . This open-label trial was conducted at 71 centers worldwide . Patients were monitored for safety and overall survival . RESULTS Therapy with vitespen is devoid of significant toxicity . Patients r and omly assigned to the vitespen arm received variable number of injections ( range , 0 to 87 ; median , 6 ) in part because of the autologous nature of vitespen therapy . Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm . Exploratory l and mark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments . Such difference was not detected for substage M1c patients . CONCLUSION These results are consistent with the immunologic mechanism of action of vitespen , indicating delayed onset of clinical activity after exposure to the vaccine . The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the c and i date population for a confirmatory study Dendritic cell (DC)‐based therapy has proved to be effective in patients with a variety of malignancies . However , an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described . In this study , 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate , alone ( n = 13 ) or in combination with low doses of subcutaneous ( s.c . ) interleukin (IL)‐2 injections ( n = 7 ) , to assess toxicity , immunological and clinical responses . Monocyte‐derived DCs were morphological , phenotypic and functionally characterized in vitro . Peripheral blood mononuclear cells ( P BMC ) , harvested from patients either prior to and after the treatment , were analysed using enzyme‐linked immunosorbent spot ( ELISPOT ) . After vaccination , 50 % of the patients tested ( seven of 13 ) from the first group and ( three of seven ) from the second , showed an increase in interferon (IFN)‐γ production in response to allogeneic melanoma cell lines but not to controls . Four of five tested human leucocyte antigen (HLA)‐A2 + patients with anti‐melanoma activity also showed specific T cell responses against peptides derived from melanoma‐associated antigens . Delayed type IV hypersensitivity reaction ( DTH ) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL‐2 . Significant correlations were found between DTH‐positive responses against tumour lysate and both disease stability and post‐vaccination survival on the stage IV patients . There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo . Furthermore , no significant enhancement was observed as a result of combining DC vaccination with IL‐2 . Our data suggest that autologous DCs pulsed with tumour lysate may provide a st and ardized and widely applicable source of melanoma specific antigens for clinical use . It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti‐melanoma immunity Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models . Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits . The active pharmaceutical ingredient in such vaccines can be DNA , RNA , protein , or peptide and can be administered naked , encapsulated , or after delivery in vitro into cells that are then adoptively transferred . One of the easiest , most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA ( mRNA ) that code for tumor antigens . We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response . We used this protocol to vaccinate 15 melanoma patients . For each patient a growing metastasis was removed , total RNA was extracted , reverse-transcribed , amplified , and cloned . Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA . Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant . We demonstrate here that such treatment is feasible and safe ( phase 1 criteria ) . Furthermore , an increase in antitumor humoral immune response was seen in some patients . However , a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials Advanced metastatic melanoma is incurable by st and ard treatments , but occasionally responds to immunotherapy . Recent trials using dendritic cells ( DC ) as a cellular adjuvant have concentrated on defined peptides as the source of antigens , and rely on foreign proteins as a source of help to generate a cell-mediated immune response . This approach limits patient accrual , because currently defined , non-mutated epitopes are restricted by a small number of human leucocyte antigens . It also fails to take advantage of mutated epitopes peculiar to the patient 's own tumour , and of CD4 + T lymphocytes as potential effectors of anti-tumour immunity . We therefore sought to determine whether a fully autologous DC vaccine is feasible , and of therapeutic benefit . Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC , matured after culture with irradiated tumour cells . Of 19 patients enrolled into the trial , sufficient tumour was available to make treatments for 17 . Of these , 12 received a complete priming phase of six cycles of either 0.9 × 106 or 5 × 106 DC/intradermal injection , at 2-weekly intervals . Where possible , treatment continued with the lower dose at 6-weekly intervals . The remaining five patients could not complete priming , due to progressive disease . Three of the 12 patients who completed priming have durable complete responses ( average duration 35 months+ ) , three had partial responses , and the remaining six had progressive disease ( WHO criteria ) . Disease regression was not correlated with dose or with the development of delayed type hypersensitivity responses to intradermal challenge with irradiated , autologous tumour . However , plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response ( P=0.05 ) and survival ( log rank P<0.001 ) . The treatment had minimal side-effects and was well tolerated by all patients . Mature , monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma , and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses Background In the present study , we have examined whether treatment of patients with metastatic melanoma with matured dendritic cell ( DC ) vaccines with or without low dose IL-2 may improve treatment outcomes . Methods Sixteen patients received DC vaccines ( DCs ) sensitized with autologous melanoma lysates and 18 patients received DCs sensitized with peptides from gp100 , MART-1 , tyrosinase , MAGE-3.A2 , MAGE-A10 and NA17 . IL-2 was given subcutaneously ( sc ) at 1 MU/m2 on the second day after each injection for 5–14 days in half of each group . DCs were given by intranodal injection . Results There were 2 partial responses ( PR ) and 3 with stable disease ( SD ) in the nine patients receiving DCs + peptides + IL-2 , and 1 PR and 1 SD in nine patients treated with DCs + peptides without IL-2 . There were only two patients with SD in the group receiving DCs + autologous lysates and no IL-2 . Median overall survival for all patients was very good at 18.5 months but this was most probably due to selection of a favourable group of patients for the study . There was no significant difference in survival between the groups by log rank analysis . Treatment was not associated with significant side effects . The quality and yield of the DCs in the preparations were generally good . Conclusions We conclude that mature DC preparations may be superior to immature DC preparations for presentation of melanoma peptides and that IL-2 may increase clinical responses to the DCs plus peptides . However , in our view the low response rates do not justify the cost and complexity of this treatment approach PURPOSE The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses . Because melanoma is immunogenic , we investigated whether a therapeutic cancer vaccine called Canvaxin ( CancerVax Corporation , Carlsbad , CA ) could enhance antitumor immune responses and thereby prolong survival . PATIENTS AND METHODS Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma , 150 received postoperative adjuvant vaccine therapy and 113 did not . The overall survival ( OS ) for the two groups was compared by Cox regression . Further survival analysis was performed by matched-pair analysis according to three prognostic variables : sex , metastatic site , and number of tumor-involved organ sites . RESULTS Five-year OS rates were 39 % for vaccine and 19 % for nonvaccine patients . On multivariate analysis , vaccine therapy was the most significant prognostic variable in this cohort ( P = .0001 ) . Analysis of 107 matched pairs of vaccine and nonvaccine patients revealed a significant OS advantage for vaccine therapy ( P = .0009 ) : 5-year OS was 39 % for vaccine patients versus 20 % for nonvaccine patients . There was a significant delayed-type hypersensitivity ( DTH ) response to adjuvant vaccine therapy ( P = .0001 ) , and OS was significantly correlated with DTH to vaccine ( P = .0001 ) but not with DTH to purified protein derivative ( PPD ) , a control antigen . CONCLUSION Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine . The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect . These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma The purpose of this study was to test melanoma vaccines consisting of peptides and immunological adjuvants for optimal immunogenicity and to evaluate laboratory immune monitoring for in vivo relevance . Forty-nine HLA-A2 positive patients with Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide , with or without immune adjuvant AS02B ( QS21 and MPL ) or IFA . Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays . The vaccines were well tolerated . In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients ( 1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA ) . The T cells produced IFN-gamma and downregulated CD45RA and CD28 . T-cell responses correlated with inflammatory skin reactions at vaccine injection sites ( P < 0.001 ) and with DTH reaction to Melan-A peptide ( P < 0.01 ) . Twenty-six of 32 evaluable patients showed progressive disease , whereas 4 patients had stable disease . The two patients with the strongest Melan-A-specific T-cell responses experienced regression of metastases in skin , lymph nodes , and lung . We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions Introduction : TA90 is a tumor-associated 90-kD glycoprotein antigen expressed on most melanoma cells , including those of CancerVax , a polyvalent allogeneic whole-cell vaccine . Previous studies have shown that a TA90 antigen-antibody immune complex ( IC ) in the serum of patients with melanoma is a marker of sub clinical tumor burden and a strong prognostic factor . We hypothesized that the induction of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine-mediated immune destruction of sub clinical melanoma cells with release of TA90 , and thereby serve as a surrogate marker of vaccine efficacy . Methods : From 1993 to 1997 , 219 melanoma patients were enrolled in a prospect i ve phase II trial of CancerVax plus bacille Calmette-Guerin ( BCG ) after complete tumor resection . Coded serum sample s were prospect ively collected and analyzed for TA90-IC before and 2 , 4 , 8 , 12 , and 16 weeks after initiation of CancerVax therapy . TA90-IC seroconverters were those patients whose negative TA90-IC values ( < .410 ) became positive ( ≥ .410 ) after initiation of CancerVax treatment . Results : Before CancerVax therapy , 51 patients had positive TA90-IC values and 168 patients had negative TA90-IC values . During CancerVax treatment , all 51 positive patients remained positive , 79 ( 47 % ) negative patients seroconverted to positive , and 89 ( 53 % ) negative patients remained negative . Seroconverters had higher 2-year rates of disease-free survival ( 59 % vs. 32 % ; P < .006 ) and overall survival ( 78 % vs. 63 % ; P < .02 ) than did patients whose TA90-IC values remained positive . Conclusions : CancerVax induces TA90-IC in melanoma patients with sub clinical disease . TA90-IC seroconverted patients have significantly improved disease-free and overall survival compared with TA90-IC positive patients . TA90-IC is an important prognostic factor that can serve as a surrogate marker for the clinical efficacy of CancerVax A total of 139 patients with disseminated malignant melanoma were enrolled in an uncontrolled Phase II trial evaluating the activity of Melacine , allogeneic vaccine incorporating Detox , immunologic adjuvant . Nineteen patients , including 18 with progressive disease , dropped out of the study prior to receiving one full vaccination course of five injections over 6 weeks . Disease presentation among study participants included skin or lymph nodes ( 34 % ) , pulmonary ( 24 % ) , visceral ( 34 % ) , and no evidence of disease ( NED ) ( 7 % ) . One documented metastatic site was seen in 41 % , two sites in 24 % , and three or more sites in 27 % of the patients studied . Objective clinical response rates for evaluable patients were CR 3 % , PR 5 % , minor response 4 % , stable 23 % , and progressive disease 65 % . Median survival from time of diagnosis for patients treated with Melacine is presently estimated at 23 months ( 45/139 patients censored ) . Median date from diagnosis of metastatic disease to study entry was 3 months . Side effects were generally mild to moderate with pain at injection site ( 37 % ) , granulomas ( 13 % ) , erythema ( 6 % ) , and flu-like symptoms ( 14 - 29 % ) predominating . Precursor antimelanoma cytotoxic T cell ( pre-CTL ) titers , in comparison with pre study evaluations , clearly increased in 42 % of the patients evaluated . Significantly extended survival characteristics were observed among patients who displayed an expansion of a population of CD57 , CD8 co-positive lymphocytes during therapy in comparison with those patients not displaying this peripheral blood lymphocyte ( PBL ) population expansion ( 34 mo vs. 12 mo , respectively , p = 0.04 ) and among those patients displaying disease stabilization or better as a clinical response ( p = 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present phase I/II study was to evaluate the safety , immune responses and clinical activity of a vaccine based on autologous dendritic cells ( DC ) loaded with an allogeneic tumor cell lysate in advanced melanoma patients . DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practice s. Fifteen patients with metastatic melanoma ( stage III or IV ) received four subcutaneous , intradermal , and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein ( HBs ) and /or tetanus toxoid ( TT ) . No grade 3 or 4 adverse events related to the vaccination were observed . Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented , as well as immune responses to HBs/TT antigens . Four out of nine patients who received the full treatment survived for more than 20 months . Two patients showed signs of clinical response and received 3 additional doses of vaccine : one patient showed regression of in-transit metastases leading to complete remission . Eighteen months later , the patient was still free of disease . The second patient experienced stabilization of lung metastases for approximately 10 months . Overall , our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients . Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation Previous studies have suggested that immunotherapy with dendritic cell ( DC ) vaccines may be effective in treatment of patients with AJCC stage IV melanoma . We examined this treatment in phase I/II studies in 33 patients with good performance status and low volume disease . Nineteen patients received DCs plus autologous lysates and 14 patients DCs plus peptides from the melanoma antigens MAGE-3.A2 , tyrosinase , gp100 , and MART-1 . Keyhole limpet hemocyanin ( KLH ) was used as a helper protein and influenza peptide was given as a positive control . DCs were produced from adherent cells in blood lymphocytes ( monocytic DCs ) , grown in IL-4 and GM-CSF without a maturation step . The DCs were injected into inguinal lymph nodes at weekly intervals ( ×4 ) , 2 weeks ( ×1 ) , and 4-weekly intervals ( ×2 ) . There were 3 responses ( 3 partial responses ) and 1 mixed response in the 19 patients treated with DCs plus autologous lysates . No responses were seen in the group treated with DCs plus peptides . Stable disease ( defined as no progression over a period of 3 months ) was seen in 4 patients in group 1 and 5 patients in group 2 . Treatment was not associated with significant side effects . We examined whether DTH skin tests or assays of IFN-γ cytokine production may be useful predictors of clinical responses . Twenty-two of 30 patients had DTH responses to KLH and 12 of 13 patients had DTH responses to the influenza peptide . Five of 15 DTH responses were seen against autologous lysates . This was strongly correlated with clinical responses . Approximately half the patients had responses to MART-1 peptide and a third to the other melanoma peptides . Similarly , cytokine production assays showed responses to influenza in 7 of 13 patients , and approximately one third of patients had responses to the other peptides . No IFN-γ responses were seen in 5 patients against their autologous lysates . There was no correlation between assays of IFN-γ production and clinical responses . The present studies suggest that autologous lysates may be more effective than the melanoma peptides used in the study as the source of antigen for DC vaccines . DTH responses to autologous lysates appear useful predictors of clinical responses , but further work is needed to identify other measures associated with clinical responses Purpose : To study the effect of autologous tumor cell vaccinations on the presence and numbers of circulating CD8 + T cells specific for tumor-associated antigens ( TAA ) in metastatic melanoma patients . To investigate the correlation between the presence of tumor-infiltrating lymphocytes ( TIL ) and circulating TAA-specific CD8 + T cells before and after autologous tumor cell vaccination with overall survival . Experimental design : Twenty-five stage III and resected stage IV metastatic melanoma patients were adjuvantly treated with a series of intracutaneously injected autologous tumor cell vaccinations , of which the first two contained BCG as an immunostimulatory adjuvant . Tumor sample s and blood sample s obtained before and after vaccination of these patients were studied for the presence of TAA-specific T cells using HLA-tetramers and results were correlated with survival . Results : In 5 of 17 ( 29 % ) melanoma patients , circulating TAA-specific T cells were detectable prior to immunizations . No significant changes in the frequency and specificity were found during the treatment period in all patients . Presence of circulating TAA-specific T cells was not correlated with survival ( log rank , P=0.215 ) . Inside melanoma tissue , TAA-specific TIL could be detected in 75 % of 16 available tumor sample s. In case of detectable TAA-specific TIL , median survival was 22.5 months compared to median survival of 4.5 months in case of absence of TAA-specific T cells ( log rank , P=0.0094 ) . In none of the patients , TAA-specific T cells were found both in tumor tissue and blood at the same time . Conclusions : These data suggest that the presence of TAA-specific TILs forms a prognostic factor , predicting improved survival in advanced-stage melanoma patients . The absence of TAA-specific T cells in the circulation suggests that homing of the tumor-specific T cell population to the tumor site contributes to the effectiveness of antitumor immunity Previous studies in small groups of patients suggested that immunization of melanoma patients with peptide epitopes recognized by T cells could induce regression of melanoma . This approach was tested in 36 patients with stage IV melanoma . The ( MHC class I – restricted ) peptides were from gp100 , MART-1 , tyrosinase , and MAGE-3 . The gp100 and MART-1 peptides had been modified to increase their immunogenicity . In half the patients ( groups 3 and 4 ) the peptides were given in the adjuvant Montanide-ISA-720 , and half the patients in both groups were given GM-CSF s.c . for 4 days following each injection . Treatment was well tolerated except for two severe erythematous responses to Montanide-ISA-720 and marked inflammatory responses at sites of GM-CSF administration in three patients . There were no objective clinical responses but stabilization of disease for periods from 3 to 12 months were seen in seven patients . Five of these were patients given the peptides in Montanide-ISA-720 . Delayed-type hypersensitivity ( DTH ) skin test responses were also seen mainly in the patients given the peptides in Montanide-ISA-720 . GM-CSF did not increase DTH responses in patients in the latter group but may have increased DTH responses in those not given peptides in Montanide-ISA-720 . Inflammatory responses around s.c . metastases or regional lymph nodes were observed in two patients . These results suggest that the peptides are more effective when given in the adjuvant Montanide-ISA-720 . Nevertheless , results from this study , together with those from a number of comparable studies , indicate that peptide vaccines are currently of minimal benefit to patients and support the need for ongoing development of new strategies in treatment of this disease PURPOSE The aim of this work was to assess immunologic response , disease progression , and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells ( DCs ) pulsed with a novel allogeneic cell lysate ( TRIMEL ) derived from three melanoma cell lines . PATIENTS AND METHODS Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine . Specific delayed type IV hypersensitivity ( DTH ) reaction , ex vivo cytokine production , and regulatory T-cell population s were determined . Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records . RESULTS The overall survival for stage IV patients was 15 months . More than 60 % of patients showed DTH-positive reaction against the TRIMEL . Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients ( P = .0014 ) . All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months ( range , 33 to 64 months ) . DTH-positive patients showed a marked reduction in the proportion of CD4 + transforming growth factor ( TGF ) beta+ regulatory T cells compared to DTH-negative patients ( 1.54 % v 5.78 % ; P < .0001 ) . CONCLUSION Our findings strongly suggest that TRIMEL-pulsed DCs provide a st and ardized and widely applicable source of melanoma antigens , very effective in evoking antimelanoma immune response . To our knowledge , this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability PURPOSE High-dose interleukin-2 ( IL-2 ) induces responses in 15 % to 20 % of patients with advanced melanoma ; 5 % to 8 % are durable complete responses ( CRs ) . The HLA-A2-restricted , modified gp100 peptide ( 210 M ) induces T-cell immunity in vivo and has little antitumor activity but , combined with high-dose IL-2 , reportedly has a 42 % ( 13 of 31 patients ) response rate ( RR ) . We evaluated 210 M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial . PATIENTS AND METHODS In three separate phase II trials , patients with melanoma received 210 M subcutaneously during weeks 1 , 4 , 7 , and 10 and st and ard high-dose IL-2 during weeks 1 and 3 ( trial 1 ) , weeks 7 and 9 ( trial 2 ) , or weeks 1 , 4 , 7 , and 10 ( trial 3 ) . Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment . RESULTS From 1998 to 2003 , 131 patients with HLA-A2-positive were enrolled . With 60-month median follow-up time , the overall RR for 121 assessable patients was 16.5 % ( 95 % CI , 10 % to 26 % ) ; the RRs were 23.8 % in trial 1 ( 42 patients ) , 12.5 % in trial 2 ( 40 patients ) , and 12.8 % in trial 3 ( 39 patients ) . There were 11 CRs ( 9 % ) and nine partial responses ( 7 % ) , with 11 patients ( 9 % ) progression free at > or= 30 months . Immune studies including assays of CD3-zeta expression and numbers of CD4(+)/CD25(+)/FoxP3(+ ) regulatory T cells , CD15(+)/CD11b(+)/CD14(- ) immature myeloid-derived cells , and CD8(+)gp100 tetramer-positive cells in the blood did not correlate with clinical benefit . CONCLUSION The results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials PURPOSE To determine clinical and immunologic responses to a multipeptide melanoma vaccine regimen , a r and omized phase II trial was performed . PATIENTS AND METHODS Twenty-six patients with advanced melanoma were r and omly assigned to vaccination with a mixture of four gp100 and tyrosinase peptides restricted by HLA-A1 , HLA-A2 , and HLA-A3 , plus a tetanus helper peptide , either in an emulsion with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) and Montanide ISA-51 adjuvant ( Seppic Inc , Fairfield , NJ ) , or pulsed on monocyte-derived dendritic cells ( DCs ) . Systemic low-dose interleukin-2 ( Chiron , Emeryville , CA ) was given to both groups . T-lymphocyte responses were assessed , by interferon gamma ELIspot assay ( Chiron , Emeryville , CA ) , in peripheral-blood lymphocytes ( PBLs ) and in a lymph node draining a vaccine site ( sentinel immunized node [ SIN ] ) . RESULTS In patients vaccinated with GM-CSF in adjuvant , T-cell responses to melanoma peptides were observed in 42 % of PBLs and 80 % of SINs , but in patients vaccinated with DCs , they were observed in only 11 % and 13 % , respectively . The overall immune response was greater in the GM-CSF arm ( P < .02 ) . Vitiligo developed in two of 13 patients in the GM-CSF arm but in no patients in the DC arm . Helper T-cell responses to the tetanus peptide were detected in PBLs after vaccination and correlated with T-cell reactivity to the melanoma peptides . Objective clinical responses were observed in two patients in the GM-CSF arm and one patient in the DC arm . Stable disease was observed in two patients in the GM-CSF arm and one patient in the DC arm . CONCLUSION The high frequency of cytotoxic T-lymphocyte responses and the occurrence of clinical tumor regressions support continued investigation of multipeptide vaccines administered with GM-CSF in adjuvant BACKGROUND Objective tumor response is a common endpoint in daily practice as well as in clinical trials to evaluate the efficacy of anti-cancer agents . Traditionally , the st and ard World Health Organization ( WHO ) criteria has been adopted in these context s. However , the recent development of new classes of anti-cancer agents and progress in imaging technology have required new methodology to evaluate response to treatment . Recently , the Response Evaluation Criteria in Solid Tumors Group ( RECIST ) proposed new guidelines using unidimensional measurement . Theoretically , the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products . To vali date these new guidelines , we have compared the st and ard WHO response criteria with the new RECIST guidelines in the same patient population . METHODS Data from 79 patients enrolled in eight prospect i ve phase II studies at Samsung Medical Center were retrospectively re-analyzed to determine the concordance between the two response criteria . The two response criteria were applied separately , and the results were compared using the kappa statistic to test concordance for overall response rate . RESULTS The overall response rate according to the WHO criteria was 31.6 % . Using the RECIST criteria , nine patients were reclassified and the overall response rate was 30.4 % . There was excellent agreement between the unidimensional and bidimensional criteria in 23 of 25 responses ( 92 % ) . The kappa statistic for concordance for overall response was 0.91 . CONCLUSIONS We conclude that the new RECIST guidelines are comparable to the old response criteria in evaluating response in solid tumors . Moreover , the new guidelines are just as simple and reproducible in the measurement of response in daily practice as they are in clinical trials High-dose interleukin-2 ( IL-2 ) is the only approved immunologic therapy for advanced melanoma , but response rates are low and significant toxicities limit treatment to otherwise healthy patients . g209 - 2 M is a nanopeptide engineered to mimic an epitope of the gp100 melanocyte differentiation protein that is recognized in a human leukocyte antigen (HLA)-restricted manner by melanoma tumor-infiltrating lymphocytes in some patients . Previous reports indicated that administration of the g209 - 2 M peptide could induce g209-reactive circulating T cells in patients with melanoma and that the combination of g209 - 2 M and high-dose IL-2 might be a more active treatment than high-dose IL-2 alone . Low-dose IL-2 is not active but has significant biologic effects , and because of a different toxicity profile , it can be offered to most patients . The primary objective of this cooperative group phase 2 study was to determine the activity of the combination of g209 - 2 M and low-dose IL-2 in advanced melanoma . Twenty-six HLA appropriate patients with advanced melanoma received subcutaneous g209 - 2 M peptide once every 3 weeks and subcutaneous IL-2 ( 5 million IU/m2 ) daily for 5 days during the first and second weeks . Patients were monitored for tumor response , toxicity , and induction of g209-reactive circulating T cells . There were no objective responses . There were no toxic deaths and no grade 4 toxicities . More than half of the patients experienced some grade 2 toxicity and one quarter experienced grade 3 toxicity . There was no convincing evidence by enzyme-linked immunospot or tetramer analysis of induction of g209-reactive circulating T cells . The combination of g209 - 2 M and low-dose IL-2 is safe and tolerable but inactive against advanced melanoma . Absence of evidence of immunization raises concerns for peptide-based immunization strategies with concurrent IL-2 AIM The aim of this study was to investigate the feasibility , safety , and clinical efficacy of patient-specific dendritic cell vaccines in patients with metastatic melanoma . A planned interim analysis was conducted on the first 20 patients . METHODS Tumor cell lines were established from metastatic tumor , exp and ed to 200 million cells , and then incubated with interferon-gamma for patients who were c and i date s for therapy . Cells were irradiated and cryopreserved . Patients underwent leukapheresis to obtain mononuclear cells that were cultured in the presence of IL-4 and GM-CSF to produce dendritic cells , which were incubated with cryopreserved , irradiated tumor cells , and then stored in aliquots of about 20 million cells for subcutaneous ( s.c . ) injections with GM-CSF once a week for 3 weeks , then once a month for 5 months . RESULTS The first 20 eligible patients included 10 men and 10 women , with a median age of 48 years ( range , 16 - 79 years ) . Three ( 3 ) patients had brain metastases , and 13 patients had experienced disease progression after biochemotherapy . At the time of vaccine treatment , 6 patients had evaluable metastatic disease , while 14 patients lacked measurable disease . Vaccine therapy was well tolerated , except for what appeared to be GM-CSF-related allergic reactions in 2 patients . Delayed-type hypersensitivity ( DTH ) tests to irradiated tumor cells were positive in 0 of 20 patients tested at baseline , but converted to positive in 8 patients ( 40 % ) . At a median follow-up of 13.8 months , there is a 95 % overall survival and a 48 % progression-free survival . Four ( 4 ) patients have already survived more than 3.0 years since starting the vaccine . CONCLUSION Based on tolerability , rate of tumor DTH conversion , and encouraging survival , the trial will continue accrual to at least 19 patients with measurable disease and 40 patients who lack measurable disease at the time of treatment MPS160 ( GRAMLGTHTMEVTV ) is a glycoprotein 100‐derived melanoma peptide that contains overlapping human leukemic antigen A2‐ , DR53‐ , and DQw6‐restricted T‐cell epitopes . In pre clinical testing , MPS160 demonstrated superior immunization and antitumor activity . In this report , the authors present the results from a clinical trial that evaluated the safety and immunologic efficacy of the MPS160 vaccine in patients with metastatic melanoma BACKGROUND The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy . A phase I/II trial was undertaken to define the feasibility , safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells . PATIENTS AND METHODS Twenty-one patients ( 17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma ) were enrolled in this study . Cytoreduction was performed in all cases prior to therapy . Autologous tumor cells were transfected with the tag7/PGRP-S gene , irradiated and injected intradermally every 3 weeks . RESULTS Vaccinations were well tolerated by all patients , without clinical ly significant signs of toxicity . Delayed-type hypersensitivity was observed in 48 % of cases . Antitumor immune response was observed in 95 % of patients . There were no complete or partial responses ; however , a minor response was achieved in one patient with renal cell carcinoma . The stabilization of neoplastic disease was observed in eight patients ( seven with malignant melanoma and one with renal cell carcinoma ) . Median time to tumor progression was 3 months . CONCLUSIONS The approach suggested here appears to be well tolerated and produces a number of durable clinical effects . Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma PURPOSE A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells . Source proteins for these peptides include MAGE proteins , MART-1/MelanA , gp100 , and tyrosinase . PATIENTS AND METHODS Thirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels , with a preceding phase I dose escalation and subsequent r and om assignment among the dose levels . Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing . Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors . RESULTS Vaccination with the helper peptide vaccine was well tolerated . Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81 % of patients . Among 17 patients with measurable disease , objective clinical responses were observed in two patients ( 12 % ) , with response duration s of 1 and 3.9 + years . Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6 + years . CONCLUSION Results of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides . There is also early evidence of clinical activity |
11,129 | 23,165,810 | Our data shows that in pain management all tested drugs can decrease pain significantly comparing with placebo ( P=0.017 ) .
In control of hemodynamic parameters ephedrine could efficiently control SBP , DBP , MAP at the time 1 min after intubation . | Propofol is a widely used anesthetic drug because of its minor complication and also its fast effect .
One of most popular complication in using this drug is pain during injection that is more sever in new generation of its components ( lipid-free microemulsion ) .
Other complications of propofol are bradycardia and hypotension .
This study compares 3 drugs with placebo in control of these complications of propofol . | The prophylactic use of small doses of ephedrine may counter the hypotension response to propofol anesthesia with minimal hemodynamic changes . One hundred-fifty patients scheduled for valve surgery were r and omly assigned into five groups ( n = 30 for each ) to receive saline , 0.07 , 0.1 , or 0.15 mg/kg of ephedrine , or phenylephrine 1.5 μg/kg before induction of propofol-fentanyl anesthesia . After induction , patient receiving ephedrine had higher mean arterial pressure , systemic vascular resistance ( SVRI ) , cardiac ( CI ) , stroke volume ( SVI ) , and left ventricular stroke work ( LVSWI ) indices . Patients received 0.15 mg/kg of ephedrine showed additional increased heart rate and frequent ischemic episodes ( P < 0.001 ) . However , those who received phenylephrine showed greater rise in SVRI , reduced CI , SVI , and LVSWI and more frequent ischemic episodes . We conclude that the prophylactic use of small doses of ephedrine ( 0.07 - 0.1 mg/kg ) is safe and effective in the counteracting propofol-induced hypotension during anesthesia for valve surgery Background and objective : This prospect i ve , double‐blind , r and omized , placebo‐controlled study compares the effects of ephedrine and ketamine on injection pain , and hypotension from propofol . Methods : After obtaining the approval of the Ethics Commitee , 75 patients ( ASA I‐II ) scheduled for elective operations with general anaesthesia were divided into three groups . Saline 2 mL ( Group S , n = 25 ) , ketamine 0.5 mg kg−1 ( Group K , n = 25 ) or ephedrine 70 μg kg−1 ( Group E , n = 25 ) were administered over 5 s after tourniquet application . After releasing the tourniquet , propofol 2 mg kg−1 was injected in 30 s. Pain was evaluated on a numerical scale ( 0‐10 ) where 0 represented no pain and 10 the most severe pain possible . Systolic , diastolic blood pressures and heart rates were recorded preoperatively , 1 min after propofol injection , before intubation and 1 , 2 and 3 min after intubation in all patients . Results : The incidences of pain in Groups S , E and K were similar ( 84 % , 80 % and 72 % , respectively ) . The mean pain score in Group K ( 2.1 , SD 3.1 ) was significantly lower than those of Groups S and E ( 4.9 , SD 2.6 and 4.6 , SD 3.3 , respectively ) ( P < 0.05 ) . The systolic and diastolic blood pressure values in Group K ( 120 ± 27 mmHg ) and Group E ( 123 ± 21 mmHg ) before intubation were significantly higher than that of Group S ( 104 ± 25 mmHg ) ( P < 0.05 ) . There was no significant difference between the mean heart rate values of the groups . Conclusions : Low dose ketamine or ephedrine pretreatment may prevent hypotension due to propofol induction . Despite the reduction in injection pain intensity after ketamine , the study drugs were found to be ineffective in lowering the injection pain incidence BACKGROUND Pain on injection is a recognized adverse event ( AE ) with propofol , an agent used to induce general anesthesia in surgical patients . Lidocame ( LID ) has been found efficacious in reducing pain on injection of propofol ; however , this type of pain may not be completely eliminated with LID . Metoclopramide ( MET ) is a dopamine receptor agonist with antiemetic and prokinetic properties used for the treatment of nausea and facilitation of gastric emptying in patients with gastroparesis . MET also has local anesthetic properties similar to those of LID . OBJECTIVE The aim of this study was to examine the effects of LID administered with 3 different doses of MET or saline on pain on injection of propofol in Japanese adults undergoing elective surgery . METHODS This r and omized , double-blind study was conducted at the Department of Anesthesiology , University of Tsukuba Institute of Clinical Medicine , Tsukuba , Japan . Japanese patients aged 20 to 67 years who were scheduled to undergo elective surgery were eligible for participation . Patients were r and omized to receive N administration of LID 40 mg + MET 2.5 , 5 , or 10 mg or saline . A rubber tourniquet was used to perform 1 minute of venous occlusion before administration of the study and control drugs , and then 25 % of the total calculated dose of propofol ( 2 mg/kg ) was injected into the dorsal vein of the h and through a 20-G N cannula at a rate of 1 mL/s . During a 10-second pause before the induction of anesthesia , patients were question ed by a blinded investigator about the pain intensity on injection . Pain intensity was assessed through the use of a 4-point verbal rating scale , with scores ranging from 0 ( no pain ) to 3 ( severe pain ) . Incidence and intensity of pain ( as assessed by mean pain scores ) were determined in each of the 4 study groups . Extrapyramidal reactions and injection-site AEs , including pain , edema , wheals , and inflammation occurring up to 24 hours after surgery were recorded by a blinded investigator . RESULTS The study enrolled 240 patients ( 126 men , 114 women ; mean [ SD ] age , 43 [ 13 ] years [ range , 20 - 67 years ] ; mean [ SD ] height , 160 [ 8 ] cm [ 133 - 181 cm ] ; mean [ SD ] body weight , 57 [ 10 ] kg [ range , 33 - 85 kg ] ) . There were 60 patients r and omized to each of the 4 study groups , which were comparable in distribution of demographic characteristics . Incidence of propofol-induced pain was significantly lower , but the intensity of pain was not less , in the groups that received LID/MET 40/5 or 40/10 ( both , 5 % ) compared with those who received LID/MET 40/2.5 or LID/saline ( 18 % and 20 % , respectively ) ( all , P < 0.05 ) . There were no reports of injection-site AEs or extrapyramidal reactions after injection of the control or study drugs in any of the study groups . CONCLUSION Among these 240 Japanese patients undergoing elective surgery , N administration of LID/MET 40/5 or 40/10 was associated with lower incidence , but not lower mean pain intensity scores , of pain on injection of propofol than LID/MET 40/2.5 or LID/saline before induction of anesthesia BACKGROUND The aims of this study were to investigate the effectiveness , safety , pharmacokinetics , and pharmacodynamics of microemulsion propofol , Aquafol ( Daewon Pharmaceutical Co. , Ltd , Seoul , Republic of Korea ) . METHODS In total , 288 patients were r and omized to receive 1 % Aquafol or 1 % Diprivan ( AstraZeneca , London , UK ) ( n=144 , respectively ) . A 30 mg test dose of propofol was administered i.v . over 2 s for assessing injection pain . Subsequently , a bolus of propofol 2 mg kg(-1 ) ( -30 mg ) was administered . Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil . Mean infusion rates of both formulations and times to loss of consciousness ( LOC ) and recovery of consciousness ( ROC ) were recorded . Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated . RESULTS Mean infusion rate of Aquafol was not statistically different from that of Diprivan ( median : 6.2 vs 6.3 mg kg(-1 ) h(-1 ) ) . Times to LOC and ROC were slightly prolonged in Aquafol ( median : 21 vs 18 s , 12.3 vs 10.8 min ) . Aquafol showed similar incidence of adverse events to Diprivan . Aquafol ( vs Diprivan caused more severe ( median VAS : 72.0 vs 11.5 mm ) and frequent ( 81.9 vs 29.2 % ) injection pain . The dose-normalized AUC(last ) of Aquafol and Diprivan was 0.71 ( 0.19 ) and 0.74 ( 0.20 ) min litre(-1 ) . The V(1 ) of both formulations were proportional to lean body mass . Sex was a significant covariate for k(12 ) and Ce(50 ) of Aquafol , and for k(e0 ) of Diprivan . CONCLUSIONS Aquafol was as effective and safe as Diprivan , but caused more severe and frequent injection pain . Aquafol demonstrated similar pharmacokinetics to Diprivan The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol . We conducted a prospect i ve , r and omized , double-blind trial on 310 patients undergoing anaesthesia . Patients were allocated to four groups according to the lignocaine dosage : group A ( control ) , no lignocaine ; group B , lignocaine 0.1 mg kg-1 ; group C , lignocaine 0.2 mg kg-1 ; group D , lignocaine 0.4 mg kg-1 . Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased Background The purpose of this study was to determine the optimal dose of remifentanil for minimizing hemodynamic changes during intubation and reducing propofol-induced pain in elderly patients . Methods In a r and omized prospect i ve study , 60 patients ( ASA I-II , elder than 65 years ) were enrolled to determine which of two target remifentanil blood concentrations ( 3 ng/ml , 5 ng/ml ) was required to blunt hemodynamic changes during intubation and to reduce propofol-induced pain . After the target effect site concentration of remifentanil had been reached , the target controlled infusion of propofol was started and propofol-induced pain was recorded . Blood pressure and heart rate were recorded at baseline , just before intubation and 1 , 3 , 5 min after intubation . Results There were no significant differences in the hemodynamic parameters between two groups , but not in arterial pressure at just before intubation and 1 minute after intubation . However , the group R5 ( 5 ng/ml ) showed significantly less intense pain induced by propofol than in the group R3 ( 3 ng/ml ) . Conclusions The results suggest that the group R5 provide more relief in propofol induced pain than the group R3 , but showed great possibility of hypotension and bradycardia in both groups , which means it should be used with caution s in the elderly patients The effects of three premeditation regimens were compared in 45 healthy patients in whom anaesthesia was induced with diprivan 2mgkg-1 i.v Premedication with diazepam 10 mg orally and droperidol 2.5–5 Omg and piritramide 7.5–15.0 mg i.m . result ed in less pain on injection and a more profound sleep fro M. Dipnvan than premedication with diazepam 10 mg orally or no premedication . No differences in speed of induction were found when cessation of counting was used as a sign of unconsciousness . When the loss of eyelash reflex was used to define unconsciousness , the oral and i.m . premedication provided quicker induction after diprivan ( 39.3±2 9s ) than no premedication ( 53.7±3.0s ) ( Background Microemulsion propofol produces more frequent and severe pain upon injection than lipid emulsion propofol . This study examined the analgesic effect of lidocaine-premixed microemulsion propofol in patients pretreated with remifentanil . The induction of anesthesia with this combination was compared with microemulsion propofol accompanied with either remifentanil or lidocaine . Methods One hundred twenty patients aged between 20 - 65 years old were allocated r and omly into one of three groups ( n = 40 , in each ) . The patients in the remifentanil group received remifentanil 0.5 µg/kg IV for 30 seconds before a microemulsion propofol injection . The patients in the lidocaine group received propofol 2 mg/kg premixed with 40 mg lidocaine over a 60 second period . The patients in the combination group received both remifentanil and lidocaine . Results There was a significantly lower incidence of microemulsion propofol injection pain ( severity 2 or more ) in the combination group ( 12.5 % ) than in the remifentanil and lidocaine groups ( 90 % and 65 % , respectively , P < 0.05 ) . The incidence of moderate pain disappeared completely in the combination group ( 0 % ) compared to that in the remifentanil and lidocaine group ( 32.5 % and 20 % , respectively , P < 0.05 ) . Severe pain did not appear in any of the three groups . There were no complications on the injection site in the lidocaine alone and combination groups . Conclusions The combination of microemulsion propofol premixed with lidocaine after a pretreatment with remifentanil was more effective in reducing the incidence of pain upon the injection of microemulsion propofol than either treatment alone The effect of diluting propofol in 5 % dextrose on the incidence of i.v . injection pain was studied in 100 adult patients . Severe injection pain occurred in 32 % ( 16 patients ) who received undiluted propofol , compared with 10 % ( five patients ) who received dilute propofol . We concluded that the dilution of propofol significantly reduced the incidence of severe pain during injection without increasing postoperative venous sequelae Propofol , a commonly used anesthetic , often causes pain on injection . Several methods have been described to reduce this pain , however , complete inhibition has not been achieved . Our r and omized , placebo controlled , double blind study has been conducted to compare the analgesic efficacy of iv pretreatment of ketamine , meperidine , thiopental , lidocaine to minimize the injection pain of propofol . 125 patients ASA I and II were r and omly allocated into 5 groups and received . Group K , ketamine 0.4 mg/kg ; Group T , thiopental 0.5 mg/kg ; Group M , meperidine 0.5 [ corrected ] mg/kg ; Group L , lidocaine 1 mg/kg ; Group S , saline 3 ml . All pretreatment drugs were made into 4 ml solutions and were accompanied by manual venous occlusion for 1 min , followed by tourniquet release and slowly IV administration of propofol . Pain was assessed with a four point scale . All treatment groups had a significantly lower incidence of pain than placebo group ( p < 0.05 ) . However , it has been observed that pretreatment with ketamine was the most effective in attenuating pain associated with propofol injection ( p < 0.05 ) . For painless injection of propofol , routine pretreatment with ketamine 0.4 mg/kg along with venous occlusion is recommended We sought to determine the effect-site concentration of remifentanil blunting sympathetic responses to tracheal intubation and skin incision during bispectral index (BIS)-guided propofol anesthesia . Forty-one ASA physical status I – II patients , aged 20–65 yr and undergoing major abdominal surgery , were r and omly assigned to one of two groups : tracheal intubation ( group TI , n = 20 ) or skin incision ( group SI , n = 21 ) . All patients received a target-controlled infusion of propofol of 4 & mgr;g/mL , which was then adjusted to maintain a BIS value ranging between 40 and 50 . The effect-site concentration of remifentanil blocking the sympathetic responses to tracheal intubation and skin incision in 50 % of cases ( Ce50 ) was determined using an up- and -down sequential allocation method . The mean ( 95 % confidence interval [ CI ] ) Ce50 of remifentanil was 5.0 ng/mL for TI ( 95 % CI , 4.7–5.4 ng/mL ) and 2.1 ng/mL for SI ( 95 % CI , 1.4–2.8 ng/mL ) . This study shows that effect-site concentrations of remifentanil of 5 ng/mL and 2 ng/mL are effective in blunting sympathetic responses to tracheal intubation and skin incision in 50 % of patients when combined with a BIS-guided target controlled infusion of propofol STUDY OBJECTIVE To compare the efficacy of alfentanil , remifentanil , and saline in minimizing the propofol injection pain . DESIGN R and omized , double-blind study . SETTING University hospital . PATIENTS 175 ASA physical status I and II , adult female patients undergoing minor gynecological procedures with general anesthesia . INTERVENTIONS Unpremedicated patients were r and omly allocated to one of four groups . Patients received 2 mL ( 1 mg ) of alfentanil ( n=43 ) , 2 mL of remifentanil 0.01 mg ( n = 43 ) , 2 mL of remifentanil 0.02 mg ( n=45 ) , or 2 mL of saline ( n=44 ) 30 seconds prior to administration 5 mL of propofol 1 % . MEASUREMENTS Patients were asked whether they had pain due to propofol injection . Their pain scores were evaluated with a Visual Analogue Scale . In the Postanesthesia Care Unit , frequency of postoperative nausea , vomiting , hypotension , and flushing were all determined . MAIN RESULT The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group ( p < 0.05 ) . When the alfentanil group was compared with the remifentanil groups , significant differences in pain relief associated with injection of propofol ( p < 0.001 ) were noted . Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg ( p < 0.001 ) . CONCLUSIONS The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group . Remifentanil was effective in preventing propofol injection pain , and should be used at a dose of at least 0.02 mg for this purpose . Remifentanil may be an alternative drug for prevention of propofol injection pain Propofol causes pain on intravenous injection in 28 to 90 % of patients . A number of techniques have been tried to minimize propofol-induced pain , with variable results . In a r and omized , double-blind , placebo-controlled trial , we compared the efficacy of ephedrine 30 μg/kg pretreatment to lignocaine 40 mg for prevention of propofol-induced pain . Ninety-three adult patients , ASA 1 and 2 , undergoing elective laparoscopic cholecystectomy were r and omly assigned to three groups of 31 each . Group 1 received normal saline , group 2 received lignocaine 2 % ( 40 mg ) and group 3 received 30 μg/kg ephedrine . All pretreatment drugs were made up to 2 ml . Pain at the time of propofol injection was assessed on a four-point scale : 0=no pain , 1=mild pain , 2=moderate pain , and 3=severe pain . Twenty-seven patients ( 87 % ) of ephedrine pretreatment patients had pain during intravenous injection of propofol as compared to 24 ( 77 % ) in the normal saline group . In the lignocaine group , propofol-induced pain was observed in only 13 ( 42 % ) when compared with other study groups ( P<0.05 ) . Pretreatment with ephedrine 30 μg/kg did not attenuate pain associated with intravenous injection of propofol , nor did it improve haemodynamic stability during induction . However , pretreatment with 2 % lignocaine ( 40 mg ) was effective in attenuating propofol-associated pain BACKGROUND Pain on injection is a common adverse effect with propofol used for general anesthesia . OBJECTIVES The aims of this study were to evaluate the analgesic effect of dexamethasone during propofol injection and investigate whether a combination of dexamethasone and lidocaine produced additional analgesic efficacy compared with either treatment alone . METHODS In a double-blind , prospect i ve trial , patients scheduled to undergo elective plastic surgery were r and omized to receive lidocaine 20 mg , dexamethasone 6 mg , combination lidocaine 20 mg and dexamethasone 6 mg , or normal saline with venous occlusion for 1 minute , followed by administration of 25 % of the total calculated dose of propofol ( 2.5 mg/kg ) into a dorsal h and vein . Pain intensity and incidence were evaluated during a 10-second pause before the induction of anesthesia , using a 4-point verbal rating scale ( 0=none , 1=mild , 2=moderate , 3=severe ) ; a score of 1 to 3 was counted as pain . Patients were monitored hourly for 24 hours postsurgery by a blinded investigator for adverse effects at the injection site ( eg , pain , edema , wheal , flare response ) . RESULTS A total of 140 ( 35 per group ) Korean patients ( 91 women , 49 men ; mean [ SD ] age , 47 [ 14 ] years ; mean [ SD ] height , 162 [ 8 ] cm ; and mean [ SD ] body weight , 60 [ 8 ] kg ) completed the study . Demographic variables were similar among groups . With respect to pain intensity , mean pain score was significantly less in the combination group than in the lidocaine or dexamethasone groups ( P<0.01 , respectively ) , although the median pain scores for all groups were 0 . The incidence of pain associated with propofol injection was reduced significantly in the combination group compared with the lidocaine or dexamethasone group ( 0 % vs 34.3 % and 37.1 % , respectively ; both , P<0.01 ) . One patient ( in the combination group ) complained of perineal itching immediately following injection ; however , this subsided within a few seconds and did not require any intervention . No other adverse effects at the injection site were observed in any patient in the 24 hours post surgery . CONCLUSION Combination lidocaine 20 mg and dexamethasone 6 mg , with venous occlusion for 1 minute , was more effective than lidocaine 20 mg or dexamethasone 6 mg alone for pain control during propofol injection in these Korean patients UNLABELLED We used a r and omized , controlled , double-blinded design to study the effect of ondansetron ( OND ) pretreatment on the pain produced by the IV injection of propofol . Eighty patients were r and omly assigned to one of two groups : Group I received 2 mL of IV 0.9 % saline pretreatment , and Group II received OND ( 4 mg in 2 mg/mL solution ) pretreatment in the dorsum of the h and , followed by propofol 1 min later . Pain was reduced significantly in the OND group ( P<0.05 ) . Approximately one third of the patients in each group had myoclonic movements or skin rashes in the limb that received propofol . We conclude that the OND pretreatment may be used to reduce the incidence of pain on injection of propofol and to prevent postoperative nausea and vomiting . IMPLICATION S In a double-blinded , controlled study , IV ondansetron ( 4 mg ) pretreatment was used to alleviate pain on injection of propofol . Ondansetron was successful in relieving pain without any adverse effect in a significant number of patients Background Propofol and alfentanil often are combined during induction of anesthesia . However , the interaction between these agents during induction has not been studied in detail . The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex , loss of consciousness , and hemodynamic function in 20 un-premedicated ASA physical status 1 patients aged 20 - 55 yr . Methods Patients were r and omly divided into four groups to receive a computer-controlled infusion of alfentanil with target concentrations of 0 , 50 , 200 , or 400 ng/ml ( groups A , B , C , and D , respectively ) . While the target concentration of alfentanil was maintained constant , patients received a computer-controlled infusion of propofol , with an initial target concentration of 0.5 - 1 micro gram/ml , that was increased every 12 min by 0.5 - 1 micro gram/ml . Every 3 min , the eyelash reflex and state of consciousness were tested and an arterial blood sample was taken for blood propofol and plasma alfentanil determination . The propofol-affentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression , and for the percentage of change in systolic blood pressure and heart rate by logistic regression . Results The patient characteristics did not differ significantly among the four groups . The patients in groups A and B continued to breathe adequately , whereas all patients in groups C and D required assisted ventilation . End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients . With plasma alfentanil concentrations increasing from 0 to 500 ng/ml , the EC50 of propofol decreased from 2.07 to 0.83 micro gram/ml for loss of eyelash reflex and from 3.62 to 1.55 micro gram/ml for loss of consciousness . With plasma alfentanil concentrations increasing from 0 to 500 ng/ml , the blood propofol concentrations associated with a 10 % decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 micro gram/ml and from 2.36 to 0.04 micro gram/ml , respectively . Conclusions Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness . In addition , alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate . Hemodynamic stability , therefore , does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia One hundred seventy-six patients ( ASA physical status I or II ) presenting for elective surgery were r and omly allocated into six study groups to compare the incidence of propofol-induced pain after pretreatment with different doses of ephedrine as compared with lidocaine . Patients in Group P ( n = 30 ) received saline placebo ; patients in Group L ( n = 30 ) received 2 % lidocaine 40 mg ; patients received ephedrine 30 & mgr;g/kg ( Group E30 , n = 28 ) , 70 & mgr;g/kg ( Group E70 , n = 30 ) , 110 & mgr;g/kg ( Group E110 , n = 30 ) , and 150 & mgr;g/kg ( Group E150 , n = 28 ) , respectively , followed 30 s later by propofol 2.5 mg/kg . A blinded anesthesiologist asked the patient to evaluate the pain score ( verbal rating scale and face pain scale ) . The incidence and intensity of pain was less in the lidocaine and ephedrine groups than in the placebo group ( P < 0.01 ) . Before tracheal intubation , the arterial blood pressure was decreased in the P and L groups , and after intubation , hemodynamics were increased in the E110 and E150 groups , respectively ( P < 0.05 ) . We concluded that pretreatment with a small dose of ephedrine ( 30 and 70 & mgr;g/kg ) reduced the incidence and intensity of propofol-induced pain with a lesser decrease in arterial blood pressure than from propofol alone in lidocaine pretreatment |
11,130 | 12,535,436 | Brushes that worked with a rotation oscillation action removed more plaque and reduced gingivitis more effectively than manual brushes in the short and long term .
There was no evidence of any publication bias .
No other powered brush design s were consistently superior to manual toothbrushes .
REVIEW ER 'S CONCLUSIONS Powered toothbrushes with a rotation oscillation action achieve a modest reduction in plaque and gingivitis compared to manual toothbrushing . | BACKGROUND Specific oral bacteria , generically known as " dental plaque " are the primary cause of gingivitis ( gum disease ) and caries .
The removal of dental plaque is thought to play a key role in the maintenance of oral health .
There is conflicting evidence for the relative merits of manual and powered toothbrushing in achieving this .
OBJECTIVES To compare manual and powered toothbrushes in relation to the removal of plaque , the health of the gingivae , staining and calculus , dependability , adverse effects and cost . | OBJECTIVES The purpose of the present study was to evaluate the effect of an electrically active toothbrush on established plaque and gingivitis in a 7-month clinical trial . MATERIAL AND METHODS For this study , 66 volunteers ( non-dental University students ) were selected on the basis of having moderate gingival inflammation . At baseline , plaque ( Quigley & Hein ) , bleeding upon marginal probing and the Modified Gingival index were assessed on the vestibular , mesio-vestibular , disto-vestibular and lingual surfaces at four sites per tooth . Subjects were r and omly divided among two groups ; one group brushed with a control brush ( Butler GUM 309 ) while the other used the electrically active test brush . After 2 weeks , 4 weeks , 4 months and 7 months the clinical indices were again recorded . At each assessment the participants received a new brush head for the electrically active brush ( test group ) or a new manual control toothbrush ( control group ) . RESULTS All baseline indices appeared to be well balanced . A mean Quigley & Hein plaque score of 1.98 and 2.13 was found in the control and test group , respectively . Little change was observed from baseline to 7 months . The mean bleeding upon marginal probing score at baseline was 0.62 for the control group and 0.59 for the test group . Little to no improvement was observed for the manual brush , whereas an increase in bleeding was observed in the test group in the course of this study . The mean percent reduction in plaque after 1 min of brushing varied throughout the study between 36 % and 46 % . No difference between the brushes was observed at any time point during the 7-month test period . CONCLUSION No beneficial effect could be shown for the ' electrically active design feature ' compared to a regular manual toothbrush control This single-blind , 8-week study compared the efficacy of a sonic toothbrush and a manual brush in 40 patients with adult periodontitis . Qualitative clinical indices and quantitative laboratory methods were used to monitor the periodontal status of 3 pockets 5 to 7 mm deep in each subject . Patients were r and omly assigned either a sonic or manual toothbrush . The two groups were comparable with respect to age , gender , and anatomical location of the test sites . Data were collected from all sites at baseline and at 2 , 4 , and 8 weeks . Over the 8-week period , both groups showed significant improvements in the clinical indices used . Descriptive statistics indicated the sonic brush group had greater improvement than the manual group in the clinical parameters ( gingival index , bleeding index , probing depth , and clinical attachment level ) . Gingival crevicular fluid ( GCF ) flow was significantly lower in the sonic brush group ( P = 0.018 ) . Considerable variation was present in the levels detected for both inflammatory cytokines tested , however , concentration of interleukin-1 beta was significantly lower in the GCF of sonic group patients ( P = 0.05 ) , while concentration of interleukin-6 was significantly reduced in both groups ( P < or = 0.05 ) ( t tests ) . Under these conditions , there is some evidence to suggest that the sonic toothbrush is more beneficial in resolving inflammation in patients with moderate periodontal disease Twenty-five subjects were assessed for plaque and soft tissue safety monitored by gingival irritation the first thing in the morning of day one following no toothbrushing for 12 - 14 hours . Subjects then brushed with either the Dentrust ( manual toothbrush ) , Crest Complete ( manual toothbrush ) or Interplak ( mechanical toothbrush ) for a timed three minutes under supervision . The toothbrush assignments were by a table of r and om numbers . Following brushing , the subjects were assessed immediately for levels of plaque and gingival irritation . The subjects were then recalled three hours later for another assessment of plaque levels and residual gingival irritation from the morning toothbrushing . After three or four days the subjects were recalled to test an alternate toothbrush . Three or four days later the subjects were recalled to test the final toothbrush . Levels of irritation severity were evaluated using st and ard soft tissue examination procedures , and after rinsing with disclosing solution and photography , with subsequent blind judging of stain intensity and area on the gingiva by a panel of three experienced investigators . In the first morning assessment there was no significant difference among plaque or gingival appearance or stain uptake levels of the three groups before using the three toothbrushes . Immediately following toothbrushing , the three groups exhibited similar levels of plaque removal and clinical or stain-related gingival irritation . There was no significant statistical difference among the plaque or safety evaluations , although the Interplak toothbrush demonstrated higher irritation levels judged by stain uptake than the manual toothbrushes . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of the present study was to test the plaque-removing efficacy of 4 different toothbrushes in relation to duration of toothbrushing . The brushes studied were a manual toothbrush ( M ) , a conventional electric toothbrush -- the Blend-a-Dent ( BL ) , the Interplak ( IP ) and the Braun Plak Control ( BPC ) . For this study , 20 subjects were selected . The study was divided into 5 experiments which differed only in respect to the brushing time . The available time in experiment 1 through 5 was 7.5 , 15 , 30 , 45 , 90 s per quadrant respectively . Prior to each experiment , all subjects were asked to abstain from oral hygiene procedures for at least 24 h. The efficacy of toothbrushing in each experiment was studied while one investigator ( MAL ) brushed the teeth of the subjects . In each subject , all 4 brushes were tested . Each brush was assigned to a quadrant in a r and om order . No toothpaste was used throughout this study . The amount of dental plaque was evaluated before and after brushing by means of the Silness & Löe plaque index at 6 sites around each tooth investigated . The results show an increase in efficacy for all brushes varying from 7.5 s per quadrant to 90 s per quadrant ( mean plaque reduction in terms of percentage 7.5 s-90 s : M = 40%-75 % , BL = 45%-82 % , BPC = 51%-94 % , IP = 64%-92 % ) . The IP removed significantly more plaque than the other 3 after 7.5 s of brushing . From 15 s through 90 s , the IP and BPC were equally effective . ( ABSTRACT TRUNCATED AT 250 WORDS Forty-seven adult orthodontic patients with fixed orthodontic appliances were divided into three study groups : ( 1 ) oral irrigation with automatic toothbrush , ( n = 16 ) ; ( 2 ) oral irrigation with manual toothbrushing , ( n = 16 ) ; ( 3 ) control group with continued normal toothbrushing only , ( n = 15 ) . Gingival and plaque indices , bleeding after probing , and gingival sulcus depths were assessed at baseline , 1-month , and 2-month periods . Marked and significant gingival and plaque improvements from baseline were measured in all three study groups . After 1 to 2 months use of the automatic toothbrush and /or the oral irrigation device , there was a significant reduction in plaque when compared with the control group who used only the manual toothbrush ( p = 0.026 ) . Also , there was a significant reduction in gingival inflammation ( p = 0.045 ) and evidence for reducing bleeding after probing ( p = 0.037 ) . No significant differences were found in probe depths among the three study groups , however , use of both devices reduced the pocket depth significantly from baseline by 0.5 mm ( p < 0.0002 ) . For this population of orthodontic patients , significant reductions in plaque , gingival inflammation , and a tendency for reduced bleeding after probing occurred in both groups with the power device . These improvements were most attributable to the effect of the oral irrigation device Twelve dentulous patients , age 65 or older , with no medical or pharmacologic predisposition to gingival hyperplasia were enrolled in a controlled clinical trial to evaluate the effect of the unaided use of an ultrasonic toothbrush on supragingival plaque and gingival bleeding . Subjects used the ultrasonic toothbrush in lieu of their conventional toothbrushes for a 30-day period . Clinical measurements of the plaque index and bleeding index were made at baseline and at 15 and 30 days . At the end of the 30-day test period , the use of the ultrasonic toothbrush result ed in significant reductions in plaque score , proportion of high plaque surfaces , and bleeding index . The reduction of the bleeding index indicates significant improvement in oral health . In this study , the use of an ultrasonic toothbrush effectively improved oral hygiene and health in a population that often exhibits decreased manual dexterity . Strategies for oral health care assessment and education for guidance of effective interventions are included in checklist form ; level of care classification , cost in both time involved and equipment , and purchase instructions also are discussed . Further study is warranted to evaluate this instrument for cognitively impaired elders , who often rely on caregivers for oral hygiene procedures BACKGROUND The purpose of this 30-day blinded , parallel- design study was to compare the effect of 2 powered toothbrushes , the Rowenta MH700 and the Braun Plak Control Ultra , on reducing plaque accumulation , gingivitis , and gingival bleeding in a cohort of 60 healthy adults . METHODS After baseline evaluation of plaque , gingivitis , and gingival bleeding , subjects were r and omly assigned to one of the experimental groups , provided written and verbal toothbrushing instructions , and had their teeth polished . At 2 weeks ( follow-up 1 ) and 4 weeks ( follow-up 2 ) all clinical parameters were again evaluated . RESULTS The Braun group demonstrated a nearly significant reduction in gingival index ( Gl ) and a significant reduction in GI at follow-up 2 . The Rowenta group demonstrated significant reductions in GI , plaque index ( PI ) , and bleeding index ( GBI ) at both follow-up 1 and 2 examinations . At follow-up 1 , the Braun group demonstrated a nearly significant reduction in GI , a significant reduction in PI , and a non-significant reduction in GBI . At follow-up 2 , the Braun group demonstrated a significant reduction in GBI , but not a significant reduction in PI . The reduction in GI for the Rowenta group was significantly greater ( P values of 0.0001 and 0.0001 , respectively ) than that demonstrated in the Braun group . However , the Rowenta group did not demonstrate a significantly greater reduction in PI ( P values of 0.7135 and 0.3184 for follow-up 1 and follow-up 2 , respectively ) or GBI than the Braun group at either examination ( P values of 0.0663 and 0.3397 for followup 1 and 2 , respectively ) . CONCLUSIONS The results of this study support the findings of numerous other studies that powered toothbrushes have great potential to remove plaque and improve gingival health and that the improvement can be demonstrated in a relatively short period of time . J Periodontol 1999;70:840 - 847 PURPOSE To compare the safety and efficacy of two oscillating-rotating power toothbrushes , the rechargeable Braun Oral-B D8 and the battery-powered Colgate Actibrush . MATERIAL S AND METHODS This was a r and omized , examiner-blind , parallel-group study , carried out over 3 months of product use , involving a total of 113 healthy subjects with a plaque score of > or = 1.5 and a gingivitis score of > or = 1.1 . Subjects were given written and verbal instructions in the use of their respective power brushes and were told to brush twice per day . At baseline , hard and soft tissues were examined , and plaque scores and gingival scores were recorded after 12 - 18 hrs of no oral hygiene . Subjects returned after 3 months , at which time soft and hard tissues were re-examined and plaque and gingivitis scores were recorded . RESULTS No evidence was found of soft or hard tissue trauma and both brushes were considered to be safe when used according to the manufacturers ' instructions . After 3 months , whole mouth plaque scores had decreased by 7 % in the D8 group but had increased by 4.3 % in the Actibrush group . The decrease from baseline in the D8 group was statistically significant , but the increase in the Actibrush group was not . The difference between the two groups was statistically significant both for the whole mouth and all individual sites . Whole mouth gingivitis scores were also reduced significantly from baseline in both groups , by 22.5 % in the D8 group and by 17.5 % in the Actibrush group . For whole mouth scores and all individual sites ( interproximal , buccal and lingual ) , the D8 was significantly more effective than the Actibrush BACKGROUND Reports suggest powered toothbrushing may provide some clinical benefit over manual tooth-brushing , but most studies have been of short duration with subjects trained in toothbrush use . The aim was to determine if the oscillating-rotating powered brush ( PB ) could safely provide clinical benefits over and above a manual brush ( M ) in subjects with no formal instruction or experience in powered brush use . METHODS This 6-month , single-masked , parallel design , r and omized clinical trial compared the PB with an American Dental Association (ADA)-accepted soft-bristle manual brush in a non-flossing gingivitis population ( n = 157 ) . Subjects were given written instructions but no demonstration on toothbrush use at baseline . Efficacy was assessed by changes in gingival inflammation , plaque , calculus , and stain , while changes in clinical attachment levels and recession measurements provided safety data . A prophylaxis was provided after baseline assessment . The 6-month plaque index ( PI ) was recorded immediately post-brushing after covert timing of the subjects , and correlation analyses were run to assess the relationship of brushing time to PI . Paired t tests , analysis of variance ( ANOVA ) , and analysis of covariance ( ANCOVA ) were used to assess within and between treatment group differences for PB ( n = 76 ) versus M groups ( n = 81 ) . RESULTS Measures of inflammation showed a statistically significant drop for both brushes at 3 and 6 months . Mean overnight full-mouth PI scores were significantly lower at 3 months for the PB ( 1.57 ) compared to the M group ( 1.80 ) , P = 0.0013 . Immediate post-brushing PI at 6 months was also significantly lower for the PB ( 1.10 ) versus M ( 1.39 ) ( P= 0.0025 ) . There was an overall negative correlation for PI and brushing time ( r = -0.377 , P= 0.0001 ) . Mean calculus index ( CI ) scores were lower for the PB at 3 ( P= 0.0304 ) and 6 months ( P = 0.0078 ) , while no significant differences in stain were observable . Clinical attachment level and recession measurements showed no significant between-group changes from baseline for either brush on canine teeth or on teeth with recession at baseline . CONCLUSION The oscillating-rotating toothbrush safely provides clinical benefits in plaque and calculus reduction over a manual brush even in subjects with no formal oral hygiene instruction The purpose of the present study was to compare in untreated patients suffering from moderate to severe periodontitis the efficacy of dental floss ( DF ) and interdental brushes ( IDB ) in the reduction of plaque , gingival inflammation , and probing depth in a 6-week period prior to subgingival debridement . Twenty-six patients ( 12 female , 14 male ; mean age 37.4 years ; range 27 to 72 years ) were instructed to use DF for one side of the dentition and IDB for the other side as an adjunct to the daily toothbrushing for 6 weeks . Oral hygiene instructions for toothbrushing and the use of the two devices were given at baseline and at week 3 . Measurements were carried out at baseline and at 6 weeks including plaque scores , probing depth , and 2 bleeding scores ( periodontal pocket bleeding index and angulated bleeding index ) . With the IDB , the approximal plaque score at baseline of 3.09 reduced to 2.15 at 6 weeks and with DF from 3.10 to 2.47 , respectively . IDB proved to remove significantly more plaque than DF . Baseline probing depth of 5.84 mm for IDB sites and 5.59 mm for DF sites was reduced to 5.01 mm at 6 weeks for both regimens . Analysis showed that the use of IDB result ed in a greater pocket reduction . Both bleeding indices were slightly reduced with IDB and DF , but no differences between devices were found . In relation to patient acceptance , more problems were observed with DF , and IDB were felt to be more efficacious . In conclusion , the results of the present study indicate that in combination with a manual toothbrush , the use of interdental brushes is more effective in removal of plaque and results in a larger reduction of probing depth than the use of dental floss . Although the differences were small , they indicate , in combination with patient preferences , that interdental brushes are to be considered preferable to floss for interdental plaque removal in patients suffering from moderate to severe periodontitis Plaque removing efficiency was compared between rotary electric and manual toothbrushes . The first part of the study included 19 dental hygiene students r and omly assigned to a " rotary " or a " manual " brushing group . The subjects were instructed to brush their teeth three minutes twice a day for three weeks either with rotary electric or with manual brushes . Then for another period of three weeks brushing techniques were reversed . The results showed that the median plaque index for all sites and for buccal and lingual sites was significantly lower in the rotary brushing group ( 28 % vs 39 % and 3 % vs 6 % , p less than 0.05 ) . During the second part of the study 10 of the students refrained from all oral hygiene procedures for four weeks in the anterior m and ibular region , i.e. from 33 to 43 . They were then r and omly assigned to a " rotary " or a " manual " brushing group . Registration s of accumulated plaque were made from photographs at baseline and after 15 , 30 and 60 seconds of brushing . ANOVA analysis of the plaque scores showed a significant difference in reduction of plaque in favour of the rotary electric brush ( p less than 0.01 ) . The results suggest that the rotary electric toothbrush removes plaque more efficiently than the conventional manual toothbrush AIM The purpose of the present study was to compare the ability of the Braun Oral-B 3D Excel power toothbrush ( BPT ) , the Sonicare power toothbrush ( SPT ) and the Philips Sensiflex 2000 ( HX 2550 ) power toothbrush ( PPT ) to control plaque and reduce experimentally induced gingivitis . MATERIAL S AND METHODS Two experiments were carried out in two different groups of subjects using a split-mouth design whereby the two halves of the m and ible which had been allowed to develop gingivitis were brushed over a 4-week period with the test toothbrushes . Experiment 1 compared the BPT with the SPT ( n = 35 ) and experiment 2 compared the BPT with the PPT ( n = 32 ) . The study used a run-in period of 2 weeks , which , together with the 3-week experimental gingivitis phase , represented the pretrial phase of the experiment . The purpose of this phase was two-fold : first , to enable the subjects to become acquainted with the two power brushes and for them to receive proper oral hygiene instruction , and , second , to develop a reasonable level of gingivitis on the m and ible . Those subjects with at least 40 % of sites exhibiting bleeding in each quadrant in the m and ible at day 21 of the experimental gingivitis phase were allowed to continue with the trial . During the next 4 weeks ( treatment phase ) of each experiment , subjects were told to brush according to a split-mouth design , the right and left sides of the mouth being r and omly allocated to a toothbrush . During this period , no rinsing with an antiseptic mouthwash or flossing was allowed and a st and ard toothpaste ( Zendium(R ) ) was used . After 1 , 2 and 4 weeks , the plaque index ( Quigley & Hein ) and the bleeding tendency on marginal probing were assessed in the m and ible . RESULTS Experiment 1 showed that the bleeding score was reduced from 1.63 to 1.12 at 4 weeks by the BPT and from 1.65 to 1.26 by the SPT . This reduction was more rapid and greater with the BPT ( P < 0.05 ) . The plaque index was reduced from 2.19 at day 21 - 1.03 at 4 weeks by the BPT , and from 2.18 to 1.20 by the SPT . The difference between the two toothbrushes was not significant . Experiment 2 showed that the bleeding score was reduced from 1.77 at day 21 to 1.07 at 4 weeks by the BPT and from 1.75 to 1.24 by the PPT . This reduction was more rapid and greater with the BPT ( P < 0.05 ) . There was no significant difference in plaque index at 4 weeks ( BPT , 1.09 ; PPT , 0.95 ) . Data from the question naire at the end of the study revealed that , in both experiments , most subjects preferred the BPT . CONCLUSIONS The data from this study show that the design and action of the Braun Oral-B 3D Excel power toothbrush are more effective in resolving gingivitis than the Sonicare & the Philips Sensiflex 2000 power toothbrushes A previous crossover study showed that a watch- and -follow instructional video improved plaque removal by an electric toothbrush compared to the use of the instructional leaflet . This study employed a parallel design to assess the value of an instructional video for plaque removal by a new model oscillating/rotating/reciprocating electric toothbrush . 2 groups of 26 dentate subjects with average oral hygiene , who had never used an electric toothbrush , participated in this single blind , r and omised parallel group design ed study . On day 1 of the study , subjects received a professional prophylaxis to remove all plaque . Oral hygiene measures were then suspended and subjects returned on day 3 when a prebrushing plaque score was recorded by plaque index and area . Subjects withdrew and either read the manufacturers instructional leaflet ( group L ) or observed the instructional video ( group V ) . Groups L and V then performed toothbrushing with toothpaste for 2 minutes and with group V brushing in time with the instructional video . Post-brushing plaque indices and areas were then recorded . Whole mouth , lingual , upper , lower , anterior and posterior but not buccal % reductions in plaque index and area were significantly greater in group V compared to group L. % plaque removal was also significantly greater by area at mid and distal sites but not mesial sites . Whole-mouth plaque reductions were 10 % greater in group V but reached > 15 % at lingual surfaces . Within group differences in plaque removal at paired sites e.g. , buccal/lingual , remained similar , suggesting that further improvement could be achieved by modifying the video to devote more time to the difficult-to-clean areas . In conclusion , in the early period of learning the use of an electric toothbrush , plaque removal can be improved by using an instructional video . Such watch- and -follow video routines could be extended to other areas of oral hygiene practice A single blind 30 day study compared the reduction of plaque and gingivitis for the Hapika Powerbrush to the Interplak ultra 10 tuft . A longitudinal parallel group design was utilized and screening evaluation was performed to determine patient eligibility prior to study enrollment , 66 subjects were entered into the study and assigned to 1 of 2 groups , each using one of the toothbrushes . At baseline , subjects received an oral soft tissue exam , a dental hard tissue exam , and were scored by the Lobene modification of the Löe and Silness gingival index ( GI ) . Plaque was then disclosed and scored both pre and post brushing using the modified Turesky plaque/debris examination and an interproximal bleeding examination was performed post-brushing . On days 15 and 30 , after an oral soft tissue and GI examination , plaque was grade d by the Modified Turesky plaque/debris exam . Subjects then brushed and were grade d by the Modified Turesky plaque/debris examination and an interproximal bleeding index examination . The results showed that both brushes provided a similar change in clinical indices . All produced a statistically significant reduction from baseline to day 30 for the gingival index ( 26.5 - 29.1 % ) , the bleeding index ( 13.8 - 24.1 % ) , and the plaque index ( 16.9 - 19.4 % ) . A comparison of pre and post brushing scores for the plaque index at 30 showed that both brushes reduced plaque similarly with a statistically significant reduction ( P < 0.05 ) from their pre-brushing plaque index scores at all time periods We compared the effects of four oral hygiene methods ( manual tooth-brushing , power toothbrushing , manual toothbrushing plus irrigation , and power toothbrushing plus irrigation ) on plaque and periodontal disease . These methods were tested both when used alone and when used in conjunction with professional mechanical oral hygiene . 108 subjects were clinical ly assessed for plaque , stain , gingival inflammation , bleeding to probing , probing depth and attachment loss , and r and omly assigned to one of the 4 oral hygiene groups . Subjects were carefully instructed in the use of their assigned method and asked to discontinue all other forms of oral hygiene . After 3-months , subjects returned for re-examination and full-month professional mechanical oral hygiene care . 3 months later , subjects returned for a final oral examination . All subjects kept a diary of use of their assigned method and were called every 2 weeks to monitor discomfort , provide reinforcement and answer questions . Results showed that all the oral hygiene methods were equally effective in reducing plaque and stain accumulation , gingival bleeding , bleeding to probing ratio and the % of pockets 4 mm or deeper . None of the oral hygiene methods was associated with injury to soft or hard tissues The purpose of this study was to compare the effectiveness of plaque removal of the Water Pik Automatic Toothbrush and Interplak brush versus the Oral B-40 manual brush . Thirty healthy patients having plaque on all tooth surfaces were admitted for this two-week , double-blind study . Patients served as their own control by brushing manually for one week , and then for a second week with a r and omly-assigned electric brush . Three plaque indexes were scored at baseline , one week and two weeks . For all these indexes , results showed that the Water Pik Automatic Toothbrush removed significantly more plaque than manual brushing . The Interplak brush removed statistically more plaque than manual brushing only with the Turesky Index . The data for all indexes have a trend toward better plaque scores for patients who used the Water Pik Automatic Toothbrush . However , statistical analysis of these scores showed that both electric toothbrushes performed equally well The purpose of this study was to test the plaque-removing efficacy of an electric brush ( Philips HP550 ) in comparison with a manual brush ( Butler Gum 111 ) in five- to ten-year-old uninstructed children . The sample included twenty-three children who were divided into two groups , each group brushing for four weeks with the assigned brush at home . After this period children were asked to brush for two minutes in a dental clinic . Plaque was scored according to the Turesky modified Quigley and Hein Index before and after brushing . Analysis shows that plaque reduction with the electric brush is significantly better than with the manual brush : 46 percent versus 25 percent reduction , respectively . Results are most marked for the lingual posterior areas . Results further indicate that using an electric brush , plaque is reduced more evenly over the dentition . Participants without previous experience with powered toothbrushes showed no problem in adapting to the electric brush In order to evaluate the effectiveness of a counter-rotational powered brush ( CRPB ) during the supportive periodontal therapy ( SPT ) phase of periodontal treatment , 40 treated patients in SPT but with insufficient plaque control were r and omly divided into equal experimental or control groups . All subjects used the same toothpaste , but the CRPB group did not use any interproximal aids . Gingivitis ( MGI ) , plaque , and bleeding on probing ( BOP ) were scored at baseline and 1 , 3 , and 6 months prior to prophylaxis in conjunction with regular SPT visits . While both groups improved from baseline , CRPB use achieved significantly lower mean plaque scores and BOP at 6 months as analyzed by repeated measures ANOVA . The CRPB also showed consistent statistically superior percentage changes from baseline result ing in a general 50 % improvement in clinical conditions compared to a 20 to 25 % improvement for control oral hygiene methods . CRPB use result ed in at least a 50 % improvement from baseline twice as often as did the control . The results of this study demonstrate more substantial and consistent improvement in periodontal conditions and plaque control effectiveness with the CRPB than the control methods that included interproximal hygiene aids . It appears that the CRPB may be a useful adjunct in maintaining reduced plaque levels and favorable gingival conditions in patients in the SPT phase of periodontal therapy BACKGROUND / AIM The purpose of the present investigation was to determine the effect of self-performed supragingival plaque removal using either manual ( Crest Complete ) or power ( Braun 3D Plaque Remover ) toothbrushing on supra and subgingival plaque composition . METHODS 47 periodontal maintenance subjects completed this single-blind 6 month longitudinal study . At baseline , sample s of supra and separately subgingival plaque were taken from the mesial aspect of each tooth in each subject using sterile curettes and individually analyzed for their content of 18 bacterial taxa using checkerboard DNA-DNA hybridization . After r and om assignment to groups receiving either a manual ( n=25 ) or power toothbrush ( n=22 ) , subjects received instruction in oral hygiene and used their assigned toothbrush 2x daily for 6 months . Clinical monitoring and microbiological sampling were repeated at 3 and 6 months . Significant differences in microbiological measures over time were sought using the Quade test and between brushing groups at each time point using the Mann-Whitney test . RESULTS Mean total counts were significantly reduced for supra- and subgingival plaque sample s in the manual group and subgingival sample s in the powered brushing group . Actinomyces naeslundii and Actinomyces israelii/gerencseriae were the most numerous organisms detected at baseline and showed the greatest reductions in counts in both brushing groups . Streptococcus constellatus/intermedius was significantly reduced in both groups , while Streptococcus mitis/oralis/sanguis was significantly reduced in the manual toothbrushing group . Mean counts of species were more markedly altered in subgingival plaque . Major reductions occurred in both groups for A. naeslundii , A. israelii/gerencseriae , Peptostreptococcus micros , Veillonella parvula , Prevotella intermedia/nigrescens , S. mitis/oralis/sanguis and S. constellatus/intermedius . All taxa examined were reduced in prevalence ( % of sites colonized ) in the subgingival plaque sample s for both brushing groups . The reductions in prevalence were greater for A. naeslundii , S. constellatus/intermedius , V. parvula , A. israelii/gerencseriae , S. mitis/oralis/sanguis , P. micros , Streptococcus mutans and P. intermedia/nigrescens . Mean prevalence was decreased more for Porphyromonas gingivalis , Campylobacter rectus/showae , Treponema denticola and Bacteroides forsythus in supragingival plaque than subgingival plaque . CONCLUSIONS The major finding was the effect of supragingival plaque removal on the composition of the subgingival microbiota . Counts and prevalence of most taxa examined were markedly decreased in both toothbrushing groups . This reduction should translate to a decreased risk of periodontal disease initiation or recurrence . Further , the decreased prevalence of periodontal pathogens in supragingival plaque lowers potential reservoirs of these species The objective of this three treatment , three period , single blind , cross-over trial was to evaluate the efficacy of three toothbrushes in a cohort of children undergoing fixed appliance orthodontic therapy . The brushes used were : ( 1 ) Dental Logic HP550 with regular brush head HP5924 ( Philips , U.K. ) ; ( 2 ) Braun Oral B Plaque Remover ( D7 ) with dedicated orthodontic brush head OD5 - 1 ( Braun AG , Germany ) ; and ( 3 ) a manual dedicated orthodontic toothbrush ( P35 , Oral B Laboratories , Calif. ) . Sixty orthodontic patients , aged 10 to 16 years and wearing upper and lower fixed appliances , were screened and recruited with parental consent . After an oral soft tissue examination at baseline , the percentage of plaque-covered tooth surfaces and gingival bleeding sites were recorded using visible plaque and gingival bleeding indexes . Each subject was r and omly allocated to one of three groups ( n = 20 ) with brushing sequences 1 - 2 - 3 , 2 - 1 - 3 , 3 - 2 - 1 . The first brush was given 2 weeks after baseline ( visit 1 ) . The time interval for using each brush was 4 weeks at the end of which visible plaque and gingival bleeding indexes were recorded and a further prophylaxis given . Statistical analysis was undertaken with analysis of variance . Data were analyzed on a site-specific basis ; buccal smooth and interproximal surfaces , lingual smooth and interproximal surfaces . At baseline the mean visible plaque index for all subjects were ; buccal smooth , 52.5 % ( + /- 22.5 % ) ; buccal interproximal , 70.5 % ( + /- 18.5 % ) ; lingual smooth , 68.5 % ( + /- 21 % ) ; lingual interproximal , 76 % ( + /- 16 % ) . At visit 1 , the plaque scores at all surfaces had reduced significantly compared to baseline , but there had been no active treatment . This was attributed to a Hawthorne effect . Subsequently , there were no significant effects on visible plaque ( or gingival bleeding ) indexes with any toothbrush at any tooth surfaces . This suggests that the new HP550 is equally effective as specifically design ed orthodontic toothbrushes in removing plaque from patients with fixed orthodontic appliances Many plaque-scoring methods are based on a subjective assessment of the amount of tooth surface covered by plaque or the presence or absence of plaque at specific sites . The 2x modified Navy plaque index is an example of the latter and requires chairside decisions from 9 zones of all buccal and lingual tooth surfaces , i.e. , up to 576 for a complete dentition . The present study describes a procedural modification to the index , whereby plaque is recorded using an established planimetric plaque area method . Scoring is then performed using an overlay away from the clinic . To test the method , plaque-area measurements were made during a 30-subject , crossover study to compare plaque removal following single toothbrushings with 3 different types of manual toothbrush . Consistent with many such studies , no significant differences in plaque removal were noted between the brushes . The method was found quick and simple at the chairside , provided a permanent record of plaque distribution and could be analysed by clinical or non clinical personnel under ideal conditions . The same method could be employed for other plaque indices based on area or site subjective decisions This study compared the effectiveness of three different types of electric toothbrushes , i.e. , Interplak , Philips , and Rotadent , with a manual multitufted toothbrush ( Blend-a-Med ) , in removing supragingival plaque and in preventing the development of gingivitis in adolescent patients with fixed orthodontic appliances . A single blind , cross-over , clinical trial was carried out in 36 adolescent patients , r and omly divided into four equal groups . Every group tested each type of toothbrush , in a different sequence . Plaque and gingival scores were recorded at baseline and after 1 and 2 months of the test period . All patients received a professional prophylaxis after each clinical evaluation , except during the test period . The analysis of the data was performed with the nonparametric Friedman test . The results demonstrated , in essence , for all parameters that the manual toothbrush was the most effective . Of the three electric toothbrushes tested , the Philips toothbrush seemed to give slightly better results than the Interplak toothbrush , whereas Rotadent very clearly gave results inferior to all others . Personal preference on the four toothbrushes used revealed that the group as a whole least preferred a manual brush . However , the answers on the question naire did not always show a logical consistency . Therefore it should be interpreted with some caution The purpose of this study was to compare the subgingival and interproximal plaque removal of a manual toothbrush to that of an oscillating counter-rotational electric toothbrush . Ninety teeth were divided into control , manual , and electric groups and test teeth received a total of 20 seconds of brushing . The teeth were then anesthetized , extracted , stained , dried , and examined with a computer-assisted video analysis system . The control group had 13.88 % plaque-free interproximal surfaces , compared to 30.57 % for the manual group and 53.23 % for the electric group . The mean subgingival plaque-free measurement was 0.05 mm for the control group , 0.64 mm for the manual group , and 1.36 mm for the electric group . The differences between the means were statistically significant for both measurements The clinical effectiveness of a manual ionic toothbrush in the removal of dental plaque and the reduction of gingivitis was evaluated . A double-blind study evaluated the effect of a small , imperceptible electric current on established dental plaque and gingivitis during toothbrushing . Sixty-four adults completed the study . Gingivitis and plaque scores were determined at baseline and after 3 and 6 months . The baseline indices of the two groups were well balanced . At each examination , the participants were instructed how to hold the toothbrush properly and reminded to change brush heads every 4 weeks . Statistically significant improvements in Löe Gingival Index scores were observed from baseline to 6 months between the control and test groups and within the test group . The Quigley-Hein Plaque Index scores also showed a significant improvement from baseline to 6 months between the control and test groups and within the test group The Sonicare sonic toothbrush and a traditional manual toothbrush were compared for efficacy in improving periodontal health in young orthodontic patients with existing gingival inflammation . A 4-week , single-blind clinical trial was employed . Twenty-four subjects , ages 11 - 17 years , who were fully bonded and b and ed with fixed orthodontic appliances were selected . Subjects were r and omly assigned to use either the manual or the Sonicare toothbrush , instructed in its use , and asked to brush each morning and evening for 2 minutes . Plaque index , gingival index , percentage of sites which bled on probing , pocket depth , and total gram-negative bacteria in a subgingival plaque sample were assessed at baseline and 4 weeks around the b and ed teeth . The results demonstrate that the Sonicare brush was significantly more effective than the manual brush in all clinical parameters . Sonicare was statistically superior to the manual brush in supragingival plaque reduction ( 57 % vs. 10 % , respectively ; p < 0.001 ) . Gingival Index scores fell by 29 percent in the Sonicare group , but only 3 percent in the manual group . Reduction of bleeding on probing was significantly greater in the Sonicare group than in the manual group ( p < 0.001 ) . The Sonicare group decreased from 78 % bleeding sites at baseline to 24.5 % after 1 month . In the manual group there was only a slight reduction in bleeding on probing ( 70 % of sites at baseline and 64.6 % sites after 1 month ) . Mean pocket depths were significantly reduced compared to baseline values in both the Sonicare and the manual groups ( p < 0.001 ) . Pocket depth reduction in the Sonicare group was , however , significantly greater than in the manual group ( 28 % vs. 6 % , respectively : p < 0.001 ) . Total gram-negative bacteria in subgingival plaque sample s from b and ed test teeth of a subset of patients were reduced in the Sonicare group ( p < or = 0.05 ) , but increased in the manual group . These results clearly demonstrate that the Sonicare sonic toothbrush is superior to a manual toothbrush in improving periodontal health in adolescent orthodontic patients with existing gingivitis This three-month clinical trial was design ed to compare the effect of an electric and a manual toothbrush on reducing primarily gingivitis and secondarily , plaque , in a cohort of 70 healthy adults . After baseline evaluation of gingivitis , soft tissue trauma , and plaque , patients were r and omly assigned to one of the two experimental groups , shown an instructional tooth brushing videotape , and had their teeth cleaned . Soft tissue trauma was again scored at 2 weeks . At 12 weeks all three clinical parameters were again evaluated . The results showed statistically significant reductions ( baseline vs. 3-month ) in both whole mouth ( p = 0.003 ) and interproximal ( p = 0.008 ) gingivitis scores for the electric toothbrush group . No significant reduction at three months compared to baseline was seen for the manual brush group . When gingivitis reductions were compared over the three-month test period , the electric brush was significantly better than the manual toothbrush in both whole mouth ( p = 0.0007 ) and interproximal ( p = 0.002 ) gingivitis reduction . No increase in soft tissue trauma and no significant differences in plaque reductions were seen for either toothbrush A 30-day study was conducted to compare a new powered toothbrush ( Rowenta Plaque Dentacontrol Plus ) with a st and ard manual ADA-approved toothbrush ( Oral-B P35 ) and two marketed powered toothbrushes ( Braun Oral-B Ultra and Sonicare ) for safety , plaque area before and after toothbrushing with dentifrice , gingivitis and bleeding on probing . The three powered toothbrushes had label directions giving somewhat different times for brushing . It was presumed that these stated times were justified on the basis of some observations or measurements of thorough cleaning . One brush , the Rowenta , had labelled time requirements involving both a flat-surface brush and an interproximal brush head . The manual toothbrush came with no recommended time reference for brushing . It was thought to assess the relative efficacy of the four toothbrushes for plaque removal and soft tissue changes , if subjects were to follow label directions . The subjects used only their r and omly assigned toothbrush during the study . Assessment s at baseline and on days 15 and 30 were performed with the subjects having not brushed for 10 - 16 hours prior to the examination ( overnight plaque formation ) . There were no side effects reported by the subjects or observed by the examiners attributed to toothbrush use at any time in the study . All groups had similar plaque levels at the beginning of the study and all toothbrushes removed statistically significant amounts of plaque after brushing . On gingivitis measurements at baseline , there were no significant statistical differences among the toothbrushes tested ; however , by day 15 the Rowenta was significantly lower than the Braun group . By day 30 , the Rowenta was statistically significantly lower than all the groups in gingivitis scores . For bleeding on probing assessment s , there were no significant statistical differences among the toothbrush means at baseline or day 15 . By day 30 , the Rowenta was statistically significantly lower than the Oral-B P35 on this measurement . The Rowenta toothbrush significantly lowered the bleeding on probing scores from baseline to day 15 and from day 15 to day 30 . The Braun , Sonicare and Oral-B P35 significantly lowered scores from baseline to day 30 , but not from day 15 to day 30 . The Rowenta toothbrush was found to be an effective device for the removal of plaque , and for significantly lowering gingivitis compared to the Braun , Sonicare and Oral-B P35 toothbrushes by the conclusion of the study . The Rowenta was significantly better than the Oral-B P35 manual toothbrush for reducing bleeding on probing over the 30 days of this study OBJECTIVES This study was design ed to test the efficacy in plaque removal and the potential for gingival abrasion of 3 electric toothbrushes . The established Braun Oral-B ' Ultra ' plaque remover ( D9 ) , the Philips/Jordan HP 735 , and the newly design ed Braun Oral-B 3D Plaque Remover ( 3D ) . MATERIAL AND METHODS This study was design ed as a split-mouth , single blind , r and omised clinical study consisting of 3 identical experiments with 3 combinations of toothbrushes ( exp 1:3D-HP735 , exp 2:D9-HP735 , exp 3:D9 - 3D ) . 40 subjects were requested not to brush their teeth 48 h prior to each examination . At this visit , both the gums and teeth were disclosed for the assessment of baseline plaque and gingival abrasion . Abrasion sites were scored as small ( < or = 5 mm ) or large sites ( > 5 mm ) . Plaque was assessed according to the Quigley & Hein index at 6 sites per tooth . The participants brushed 60 s with the 2 brushes , each brush in 2 r and omly selected contra-lateral quadrants . RESULTS The increase in number of small abrasions after brushing ( exp . 1 ) was 1.2 versus 1.7 for 3D and HP735 , respectively ( ns ) ; In exp . 2 the increase was 0.9 for both D9 and HP735 . In exp . 3 the increase was 0.4 sites for both D9 and 3D . Comparison of the 3D and HP735 showed a mean plaque reduction of 67 % and 54 % , respectively ( p<0.05 ) ; when the D9 and HP735 were compared , a mean plaque reduction of 70 % and 58 % , respectively , was found ( p<0.05 ) ; a mean plaque reduction of 74 % was found in the comparison of D9 and 3D . CONCLUSION The results show that the potential gingival abrasion after brushing is comparable for all 3 electric toothbrushes . In addition the longer the subjects used the brushes the less abrasion occurred . Finally both 3D and D9 were more effective than the HP735 in removing plaque Orthodontic patients with fixed appliances have an increased risk for caries and gingivitis . Therefore , the use of special toothbrushes and additional cleaning tools is recommended . The aim of this longitudinal study was to compare the plaque removal efficacy and reduction of gingivitis from using a powered toothbrush compared to a manual toothbrush in patients with fixed orthodontic appliances . Eighty subjects were included in the study with a mean age of 13.53 years . After a baseline examination , patients were r and omly assigned to two groups and their teeth were professionally cleaned . The patients were assessed at baseline , two and four weeks using the QHI and SBI . The results showed a significantly superior plaque removal effect ( p = 0.0001 ) and reduction of gingival inflammation ( p < 0.05 ) in those patients using the powered versus the manual toothbrush . The findings were for both whole mouth and partial mouth assessment s. In accordance with previous studies , it was demonstrated that the use of a powered toothbrush can be recommended for orthodontic patients with fixed appliances This clinical study compared the effect of Colgate Actibrush , a battery-powered toothbrush , and Colgate Plus Diamond Head , a full-head , soft-bristled manual toothbrush , on established supragingival plaque and gingivitis over a 30-day period . Sixty-two healthy adult men and women were entered in the study . The subjects were stratified into two balanced groups according to their mean baseline plaque and gingivitis scores . Each group was r and omly assigned to the use of one of the two toothbrushes . Subjects were instructed to brush their teeth at home twice daily ( morning and evening ) for 1 minute with their assigned toothbrush and a commercially available tooth-paste for the 30-day duration of the study . Gingivitis and plaque examinations , as well as a soft-tissue evaluation , were conducted by the same dental examiner at baseline and after 15 and 30 days of toothbrush use . Plaque and gingivitis scores were reduced significantly from baseline after the use of both toothbrushes for 30 days . However , improvement in both supragingival plaque and gingivitis scores was significantly greater in the group using Colgate Actibrush . In conclusion , although both toothbrushes provided a significant plaque and gingivitis benefit when used as part of a normal oral hygiene regimen , the efficacy of the Colgate Actibrush was demonstrated to be superior to that of the Colgate Plus Toothbrush after 30 days of use The aim of this 12-month parallel design controlled clinical trial was to assess the effect of the Braun Oral-B Plak Control electric toothbrush on supragingival plaque and gingival health , and to compare it with a conventional soft manual toothbrush ( Jordan ) . A total of 111 patients aged between 20 and 63 years , from a general population , with bleeding on probing at 30 % or more of all sites examined were entered into the study . At baseline , immediately after periodontal examination , all volunteers received a thorough scaling of their teeth . Volunteers in both groups were told to brush their teeth for 2 min 2 x a day . Oral hygiene instruction was given at the start of the study and was not repeated . At 3 , 6 and 12 months , assessment s were carried out by a single clinician who was not aware which group the volunteers belonged to . Analysis of results demonstrated that over the 12 months of the study , the Braun Oral-B Plak Control was significantly more effective in improving gingival health than the manual toothbrush . There was , however , no difference between the 2 groups in terms of plaque removal , with the number of sites with visible plaque decreasing by a similar amount in both groups . In conclusion , results indicate that the Braun Oral-B Plak Control toothbrush is safe and more effective than a manual toothbrush in improving gingival health Three power toothbrushes with different mechanical principles ( blend-a-dent master-vertical oscillating system , blend-a-dent medic electric elliptical oscillating system , interplak-contra-rotationsystem of the bristle-tuft ) and a conventional h and toothbrush were investigated in 60 oral hygiene-motivated persons in a three-month- study . Efficiency was tested by two parameters ( plaque index , papillary-bleeding index ) under statistically identical conditions . The study showed no major differences in efficiency between the power toothbrushes and the manual toothbrush . --For the whole study the power toothbrush with an elliptical oscillating system showed the best results . --Power toothbrushes are not more effective in plaque removal than a manual toothbrush . The great statistical variation of the investigated parameters in each group shows that an optimal brushing technique was more important than the choice of a certain toothbrush . --The investigation of the interproximal areas showed that a toothbrush alone is not effective enough . The additional use of dental floss and /or interdental cleaners for optimal oral hygiene is essential This study tested the effectiveness of a rechargeable electric toothbrush , Interplak , in removing supragingival plaque and resolving gingivitis . Forty adults with gingivitis were r and omly assigned to either a " manual " or " electric " group . Detailed oral hygiene instructions were given and a blind examiner assessed plaque scores before and after brushing , toothbrush abrasion , and gingival inflammation at baseline , 1 , 2 , and 4 weeks . Subjects using the electric brush had significantly lower ( P less than 0.05 ) mean plaque and gingival inflammation scores . The electric group 's plaque scores fell from 77 % at baseline to 28 % ( before brushing ) and 14 % ( after brushing ) at 4 weeks ; the manual group 's dropped from 75 % to 50 % and 30 % ( before and after brushing , respectively ) . The mean G.I. for the electric group fell from 1.65 at baseline to 1.28 at 4 weeks , while the manual group 's scores decreased from 1.65 to 1.43 . The results suggest that the electric brush removed supragingival plaque and resolved gingivitis better than the manual brush over a 28-day period . However , a telephone survey conducted 6 months later indicated that most subjects were not using the device twice a day as they had during the study This study compared counterrotational-action power toothbrushing with manual toothbrushing in effectiveness on plaque control and gingival health in 20 r and omly selected orthodontic patients at the University of Missouri-Kansas City . A blind two-group crossover design was used . Gingival and plaque scores were recorded , and a prophylaxis was given to bring the plaque score to zero . Ten subjects received counterrotational power brushes , and ten subjects received manual brushes . Instructions appropriate to each brushing method were given by a hygienist . At 30 and 60 days , plaque and gingival scores were recorded and a prophylaxis was given . At 60 days the subjects who were using power brushes were switched to manual brushes , and the subjects who were using manual brushes were switched to power brushes . At 30 and 60 days , plaque and gingival scores were recorded and a prophylaxis was given . Plaque and gingival scores were significantly less ( p less than 0.01 ) after brushing 2 months with the counterrotational power brush than with the manual brush . This finding was irrespective of the sequence in which the brushes were used The purpose of this study was to investigate whether orthodontic toothbrushes were superior to classical toothbrushes in the elimination of microbial dental plaque on teeth and brackets and in the maintenance of periodontal tissue health in patients , ages 12 to 22 years , with fixed appliances . Twenty patients undergoing orthodontic treatment with fixed appliances and brushing with the Bass technique were included in the study . Ten patients used the Oral B Ortho type toothbrushes ( Oral B Laboratories Ltd. ) , whereas the remaining 10 patients used the Oral B Plus 35 type toothbrushes . Quigley-Hein plaque index , bonded bracket index , sulcus bleeding index , and periodontal pocket depth measurements were made at the beginning of the study and a month later . No statistically significant difference was found for plaque , sulcus bleeding , and periodontal pocket depth between Oral B Ortho and Plus 35 groups when the preinvestigatory and postinvestigatory measurements for the vestibular and proximal surfaces of upper and lower teeth were compared . This short-term study concluded that the Ortho-type toothbrush is not superior to the Plus 35-type toothbrush OBJECTIVES To compare the cleaning efficacy of a powered toothbrush with 3-dimensional brush head action ( Braun Oral-B 3D Plaque Remover D15 ) and a high-speed " microtation " brush with an additional " microbrush-clip " ( Rowenta Dentasonic MH921S ) . MATERIAL AND METHODS 82 healthy subjects took part in the study . After a familiarization period of 8 days , the subjects abstained from all oral hygiene procedures for 48 h. After plaque was scored , the subjects brushed their teeth under supervision with the two brushes according to a split-mouth design . Immediately after brushing , subjects completed a question naire and plaque was scored again . RESULTS The overall plaque scores were found to be significantly reduced from 3.05+/-0.60 to 1.96+/-0.63 by the D15 and from 3.02+/-0.58 to 2.24+/-0.64 by the Dentasonic ( p<0.05 ) . The proximal surface plaque scores were reduced from 3.20+/-0.63 to 2.17+/-0.69 by the D15 and from 3.17+/-0.60 to 2.44+/-0.69 by the Dentasonic . The relative plaque reduction was overall 36.6+/-12.2 % for the D15 compared to 26.1+/-13.5 % for the Dentasonic and at proximal surfaces , 33.1+/-12.3 % and 23.2+/-13.0 % , respectively . 75 % of the subjects stated that they would prefer to keep the D15 . CONCLUSIONS Both brushes were able to remove a significant amount of plaque , but the D15 was significantly more effective compared to the Dentasonic . The additional " microbrush-clip " for the proximal embrasures failed to improve plaque removal from these tooth surfaces , compared to the D15 alone Effective plaque control of the primary dentition can be particularly difficult to achieve because of problems with motivation and manual dexterity in some children . This study compared plaque control efficacy of a new electric toothbrush design ed specifically for use by children with a children 's manual brush . Results showed that in a pediatric population aged between 8 and 12 years , the electric brush achieved significantly greater plaque removal from both primary and permanent dentition Aim : To evaluate an oral health awareness campaign in an adult population . Design / Setting : Four workplaces in north-east London were selected , matched in two pairs and r and omly allocated to test and control groups . Completion occurred in 1995.Subjects : 98 volunteer employees in good general health . Interventions : Two oral examinations were carried out , six weeks apart . The test group received the programme immediately after baseline examination and the controls after the second visit . Main outcome measures : Gingival bleeding on probing ( BOP ) and probing depths ( PD ) were measured on each occasion using a controlled pressure probe . Results : The mean percentage of sites with BOP per subject reduced from 56 % to 25 % in the test group , while remaining static in the control group at 46 % to 48 % . The mean percentage of sites probing 4 mm and above per subject reduced from 38 % to 25 % in the test group and from 28 % to 25 % in the control group . These differences between groups were statistically significant when su bmi tted to analysis of covariance ( P < 0.001 ) . Conclusions : The study showed the clinical effectiveness of a workplace-based oral health awareness campaign , which is ideally suited to the skills and re sources of the primary care dental Abstract Power toothbrushes require less force for plaque removal than manual brushes . In addition , in vitro studies have indicated that brushing with low force could occlude patent dentin tubules by formation of a smear layer . Hence , lessening the force necessary to remove plaque may reduce dentin hypersensitivity . However , it was recently suggested that the use of an oscillating/rotating power toothbrush could decrease tooth sensitivity as compared to a sonic power toothbrush . Therefore , the objective of the present research was to compare the effect on dentin hypersensitivity of two different types of power brushes , the Optiva Sonicare and the Braun Oral B Ultra Plaque Remover . The null hypothesis was tested in an 8-week , r and omized , parallel group , examiner-blind clinical trial . Fifty-nine subjects with a history of dentin hypersensitivity participated . Dentin hypersensitivity-associated pain was elicited using tactile and evaporative stimuli and assessed using a visual analog scale ( VAS ) instrument . Clinical examinations were carried out at screening and baseline and repeated after 8 weeks of twice daily use of the power brushes . Data analysis was performed on VAS scores obtained at the final visit following adjustment for group differences at baseline . A 35 % to 40 % reduction in pain as compared to baseline was observed in both treatment groups . Treatment-related differences were not statistically significant . A gender-related effect on dentin hypersensitivity was observed using the tactile stimulus and may merit further investigation PURPOSE To evaluate and compare the oral hard and soft tissue safety and the plaque-removing efficacy of a children 's power toothbrush ( Braun Oral-B Kids ' Power Toothbrush-D10 ) and a manual toothbrush in children from a general population . MATERIAL S AND METHODS Seventy children aged 6 - 11 yrs were enrolled into a single-blind , r and omized , parallel- design study . At baseline , oral hard and soft tissues were evaluated and plaque was assessed on buccal and lingual surfaces of all fully erupted permanent and primary teeth using the Turesky Modification of the Quigley-Hein Plaque Index . Eligible subjects were r and omized to use either a Braun Oral-B children 's power toothbrush ( D10 ) or a manual toothbrush for the duration of the study . Subjects were instructed to brush their teeth at home twice daily for 1 min each day for the 30-day study period . At baseline and after 15 and 30 days , plaque was assessed following 12 - 18 hrs of no oral hygiene . In addition , at each visit single-use plaque removal was evaluated after subjects had brushed their teeth for 1 min under supervision . Oral hard and soft tissues were assessed for safety before and after the supervised 1-min brushing at each visit . RESULTS There were no pre-brushing oral hard and soft tissue abnormalities or post-brushing changes in oral tissues in either group . There were statistically significant reductions in mean plaque index for the whole mouth ( P < 0.006 ) , buccal surfaces ( P < 0.0001 ) and anterior teeth ( P < 0.008 ) from day 0 to day 30 in the D10 group , but not in the manual group . Greater mean changes in whole mouth plaque reduction were seen for the D10 group as compared to the manual group at days 15 and 30 ( P < 0.05 ) . Results from the single-use supervised brushing at each visit revealed that reductions in mean whole mouth plaque were statistically significant in both groups at each visit ( P < 0.0001 ) . There was statistically significantly greater plaque removal after a single brushing at day 0 in the D10 group compared with the manual group ( P < 0.002 ) , but the difference was not significant at days 15 and 30 A clinical trial , based on the guidelines of the American Dental Association , was conducted to evaluate the efficacy and safety of Bio-Bright , a new manually rotating toothbrush . The brush was used by 28 adults and compared to a group of 26 adults who used an ADA-accepted toothbrush ( Oral-B 35 ) . Examinations were recorded for safety , plaque level , gingival inflammation and gingival bleeding at baseline , 15 days and one month . Analysis of the data revealed no statistically significant differences between the two groups at any of the measurement periods . When calculating the cumulative longitudinal effect on plaque increase or decrease , a consistent and statically significant advantage was revealed for the Bio-Bright group , as compared to the control . No significant differences were demonstrated when comparing safety , gingival , and bleeding indices between the two groups The purpose of this study was to determine whether daily use of a rotary electric toothbrush ( Rota-dent , Prodentec Corp. , Batesville , Ark. ) and a 0.05 % sodium fluoride ( NaF ) rinse would significantly reduce decalcification when compared with manual toothbrushing only ( control group ) or manual toothbrushing and daily use of a NaF rinse ( rinse group ) . All three groups used a st and ard fluoride toothpaste . Ninety consecutive adolescent patients who were to receive orthodontic treatment were placed into one of three groups according to age and sex criteria . Decalcification was evaluated single blind by two calibrated examiners on the facial surfaces of all permanent teeth before appliances were placed ( baseline ) and 3 months after appliances were removed ( posttreatment ) . Data were analyzed by analysis of covariance with the dependent variable derived by subtracting the baseline decalcification scores from the posttreatment scores and using the baseline scores as the covariate . The results showed that although there were no significant differences between the three groups at baseline , the Rota-dent group showed significantly ( p < 0.05 ) less posttreatment decalcification than either the control or rinse groups . In a separate analysis of first molars , the Rota-dent group again showed the least decalcification and the control group showed the most . These data suggest that twice daily use of the Rota-dent electric toothbrush with a st and ard fluoride toothpaste and once daily use of a 0.05 % NaF rinse is more effective for preventing decalcification in adolescents during orthodontic treatment with fixed appliances than either conventional toothbrushing with a fluoride toothpaste , or similar toothbrushing and toothpaste with a once daily NaF rinse Two single-blind clinical studies investigated the stain removal properties of Sonicare , a new electronic toothbrush that combines sonic vibrations and dynamic fluid activity with mechanical scrubbing to clean tooth surfaces . In one study , 30 subjects used a 0.12 % chlorhexidine mouthrinse ( Peridex ) for two weeks to accumulate stain , and then were assigned to either Sonicare or a manual toothbrush ( Oral-B P-35 ) . The subjects brushed with their assigned device for 2 minutes twice a day . In a second study , 19 subjects with extrinsic stain due to coffee , tea , or tobacco ( CTT ) causes were r and omly assigned to either Sonicare or a manual toothbrush ( Crest Complete ) . These subjects also brushed for 2 minutes twice a day , with additional brushing on the stained areas . Stain on the labial surfaces of the subjects ' anterior teeth was evaluated with the Lobene index at the pretrial , 2-week , and 4-week periods . Clinical analysis indicated that use of Sonicare result ed in Peridex stain reductions of 54 % and 50 % after 2 and 4 weeks , respectively , and reductions in CTT stain of 39 % and 82 % at similar time points . The manual toothbrush result ed in stain increases of 4 % and 24 % in the Peridex study and CTT stain decreases of 41 % and 39 % after 2- and 4-week brushing periods . Computer image analysis was performed on photographic records from the CTT stain study and showed a high correlation with the Lobene index ( r = 0.82 ) . The results of these two independent studies indicate that Sonicare is superior to the manual toothbrushes studied in removing both Peridex and CTT stains . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE The aim of this study was to compare the effectiveness of the automated Interclean Interdental Plaque Remover with that of interdental brushes and Ultrafloss . METHOD AND MATERIAL S The interdental hygiene effectiveness of 35 healthy patients suffering from gingivitis was studied by an examiner daily over a period of 1 week . The sizes of the interdental spaces were classified and corresponding-sized interdental brushes or floss was selected . In a r and om , split-mouth design both interdental cleaning methods , mechanical and manual , were applied while the patients continued to use st and ard brushing techniques . Disclosed proximal plaque , the papillary bleeding index , and interdental bleeding tendency on stimulation were evaluated . RESULTS The papillary bleeding index was reduced from an average value of 40 % to 25 % . Only 5 % of interproximal plaque remained after manual interdental cleaning , whereas 40 % of plaque was still present after use of the Interclean device . Cleaning efficiency of manual and mechanical methods was comparable in only 1 interproximal space size . At the end of the study , the interdental bleeding on stimulation was significantly higher in the automatically cleaned interspaces than in the manually cleaned spaces . CONCLUSION Manual interproximal cleaning was more effective than the automated device AIMS The clinical effects and gingival abrasion aspects of 2 electrical tooth-brushes ( Braun Oral-B Plak Control Ultra and the novel development Braun Oral-B Plak Control 3D ) were to be compared with conventional manual tooth-brushing . MATERIAL AND METHODS In a cross-over study , 26 dental student volunteers participated and were assigned to 1 of 3 groups . Following instruction in the use of the electric as well as manual toothbrushes , the volunteers were timed for 2 min each day to apply one electric or the manual toothbrush , respectively , during 3 experimental phases of 2 weeks . No other methods of tooth cleaning were to be performed except the one specified for the respective test period . When brushing manually , the Bass toothbrushing technique was applied . Between each test period , a recovery period of 1 week was allowed during which no oral hygiene was performed at all . At the start and the end of each of the experimental periods , the extension of plaque deposits from the gingival margin in coronal direction was assessed using the Turesky et al. modification of the Quigley and Hein plaque index . Presence or absence of gingival inflammation was evaluated by bleeding and probing ( BOP ) . The extent and severity of gingival abrasions were assessed by use of a modified method of Breitenmoser et al. and adapted by Danser et al. RESULTS The plaque-reducing effect was similar in all groups with the same cleaning regime . For that reason , the result of the different experimental phases with the respective cleaning modalities were collapsed . Cleaning with the Braun Oral-B Plak Control Ultra electric toothbrush result ed consistently in the lowest plaque scores when compared to both the Braun Oral-B Plak Control 3D and the manual toothbrush . Although the differences in plaque reduction were statistically significant between cleaning with Braun Oral-B Plak Control Ultra and 3D , they were small and of question able clinical relevance . No significant differences in plaque reductions were found between manual brushing and any of the 2 electric brushes . Gingival abrasions were least pronounced following brushing with the Braun Oral-B Plak Control 3D electric toothbrush . However , no significant differences in gingival abrasion were encountered following brushing with the Braun Oral-B Plak Control Ultra electric in comparison with the manual toothbrush . CONCLUSIONS The results of the present study have shown that in a group of dental students trained in manual brushing technique , where efficacy was similar with the 3 toothbrushes tested , there is no evidence of greater gingival abrasion with either Braun Oral-B Plak Control Ultra or 3D when compared with a manual brush The purpose of this study was to evaluate the safety and efficacy of the Braun Plak Control for the removal of supragingival plaque and improving gingival health in a long-term clinical trial , and to compare it to regular manual toothbrush . Assessed were plaque accumulation , amount of gingival inflammation , gingival bleeding on probing , and calculus . In total , 77 young individuals were selected on the basis of having ' moderate gingivitis ' . They were monitored over 8 months and divided among 2 groups ; a control group that used a manual toothbrush and a test group that used the Braun Plak Control . The clinical assessment s were repeated after 1 , 2 , 5 , and 8 months . At baseline , subjects were h and ed their assigned toothbrushes together with written oral hygiene instructions . They were instructed to brush for at least 2 min . 1 month after baseline examinations , all subjects received a professional prophylaxis and oral hygiene instruction from an experienced dental hygienist . Plaque removal was reinforced at the 2- and 5-month examination . In conclusion , results indicate that the Braun Plak Control is a safe and efficient home care device . At the end of this trial , this electric toothbrush proved to be more effective than a regular manual toothbrush Thirty clinical recall patients from the University of Missouri at Kansas City School of Dentistry participated in a 4-week study to determine the long-term effectiveness of the INTERPLAK Home Plaque-Removal Instrument compared to manual brushing and flossing . Patients were divided into two groups , with each group using the INTERPLAK device for 2 months and the manual brush for 2 months . Patients were assessed according to measured indices for plaque , bleeding , crevice depth , and calculus . The study found that both kinds of brushes significantly reduced plaque , bleeding , and crevice depth ; however , only the INTERPLAK brush reduced calculus . Improvements on all indices were greater for the INTERPLAK device than they were for manual brushing and flossing . At the end of the 4 months , most patients indicated that they would continue to use the INTERPLAK device The purpose of the present study was to compare the Braun/Oral-B Plak Control ( D7 ) and Sonicare ( S ) in their plaque-removing efficacy . For this study , 35 university students ( non-dental ) were selected . This was a 2-part study . Prior to each appointment , all subjects were asked to abstain from all oral hygiene procedures for at least 24 h. In Part 1 , the efficacy of the toothbrush was studied when one of the investigators brushed the teeth of the panellists . In Part 2 , the efficacy of toothbrushing was studied after the students had received professional instruction . The available time for the brushing amounted to a total of 2 min per mouth . Dental plaque was evaluated by means of the Silness and Löe plaque index assessed at 6 sites per tooth . Results showed that both in Part 2 and Part 1 the D7 removed significantly more plaque than the S-electric toothbrush . The plaque reduction assessed according to Silness and Löe in Part 1 was for the D7 , 1.28 and for the S , 1.12 . In Part 2 , the reductions were 0.90 and 0.80 , respectively . The majority ( n = 34 ) of subjects preferred the D7 over the S. In conclusion , the results of the present study show that the oscillating/rotating toothbrush ( Braun/ Oral-B Plak Control ) is more effective in plaque removal than the sonic electric toothbrush ( Sonicare ) . In addition , given a choice , the panellists preferred the oscillating/rotating electric toothbrush BACKGROUND The greater effectiveness of the power toothbrush compared with a manual toothbrush is well-documented . Despite this , acceptance by dental professionals is still low . METHODS This general practice study evaluated the effectiveness of a power toothbrush ( Braun Oral-B Ultra Plaque Remover , Braun GmbH ) in 16,903 patients , based on the clinical opinions of dental professionals in regard to patients ' changing oral health status . In addition , a survey assessed the attitudes of dental professionals and patients toward the power toothbrush . RESULTS The power toothbrush was considered by dental professionals to have had a positive effect on the oral health of 80.5 percent of their patients ; the noticeable benefits with respect to a number of clinical criteria included plaque removal and improved gingival condition . Most patients in the study ( 88.9 percent ) reported that they would continue using the power toothbrush once the study was completed . At the end of the study , many more dentists and hygienists considered the power toothbrush to be the most effective way of brushing , and almost 70 percent said that they would now be more likely to recommend a power toothbrush to their patients . CONCLUSIONS The power toothbrush improved the oral health of patients in this practice -based study , and the number of dental professionals who said they would recommend a power toothbrush increased markedly during the study . CLINICAL IMPLICATION S Enabling dental professionals to evaluate the effect of a power toothbrush reinforces the findings from controlled clinical studies and increases their awareness of its potential to improve oral hygiene The aim of this 3-group , 3-treatment , single-blind , parallel group study was to evaluate and compare the efficacies of the Philips/Jordan HP735 powered toothbrush , the Braun/Oral-B D7 powered toothbrush , and the Oral-B Advantage B35 manual toothbrush in young adults ( 18 - 25 years ) . Full mouth mean ( SD ) modified Turesky Plaque Index ( PI ) and the Löe & Silness Gingival Index ( GI ) were recorded at baseline . After 24 hours abstinence from oral hygiene , the PI was recorded and each subject was given one of the test brushes with detailed instructions for use . Each subject then brushed under supervision for 90 seconds , during which time mean ( SD ) toothbrushing forces ( TBF ) were recorded . PIs were recorded immediately after brushing , and the subjects were then discharged for 6 weeks to use the allocated toothbrush at home . After 6 weeks , PI , GI and TBF were again recorded . There were no significant differences ( ANOVA ) for PI and GI between groups at baseline , or for PI following brushing at 24 hours . After 6 weeks , the powered brushes produced lower mean PI ( SD ) scores than the manual brushes , but the differences were significant only at interproximal sites . Mean GI scores for the HP735 group were similar at baseline and at 6 weeks , although for the other brushes the GI scores actually increased over this period . Mean ( SD ) TBF ( grams/force ) at baseline and 6 weeks , respectively , for the brushes were ; HP735 233 ( 205 ) , D7 159 ( 58 ) , B35 279 ( 122 ) ( p = 0.026 ) : HP735 194 ( 86 ) , D7 141 ( 57 ) , B35 297 ( 113 ) ( p = 0.0001 ) . The within-group variability for the HP735 TBF reduced considerably over 6 weeks , which is possibly because of the click-force threshold feature of this brush Initial investigations have demonstrated the effectiveness of a new contra-rotary powered electric toothbrush in removing plaque supragingivally , subgingivally , and interproximally following a single use . The purpose of this study was to evaluate the effectiveness of a counter-rotary toothbrush following 1 ) one time instruction , 2 ) reinstruction and 1 week practice ; and 3 ) a third instruction and 3 weeks of practice and home use . Twenty-four patients were studied ; 12 using the counter-rotary toothbrush and 12 using a conventional toothbrush . Using O'Leary and Turesky plaque indices , both brushes significantly reduced supragingival plaque from baseline at all intervals . The counter-rotary brush , however , was more efficient than the conventional brush at all intervals ( P less than 0.01 ) . Using a Surface Area Plaque Index , both brushes significantly reduced supragingival plaque from baseline at all intervals but there were no significant differences between brushes . A timed bleeding index showed significant reduction in gingival bleeding following 28 days of brushing with both brushes . Again , the counter-rotary toothbrush was superior to the conventional toothbrush ( P less than 0.01 ) PURPOSE To evaluate the efficacy and safety of two oscillating/rotating toothbrushes , ( Braun Oral-B Plaque Remover-D7 and Braun Oral-B Ultra Plaque Remover-D9 ) and a manual toothbrush with respect to removing extrinsic dental stain . MATERIAL S AND METHODS This r and omized , three-way cross-over study investigated 24 subjects entering the trial , which was divided into three , 5-day periods . Over the first 4 days of the study , an intense chlorhexidine/tea rinsing regimen was employed to induce extrinsic tooth staining . On day 5 , each subject was assessed for tooth stain ; they then brushed for a total of 2 minutes with one of the three r and omly allocated toothbrushes . Stain evaluations were repeated after 30 seconds , 1 and 2 minutes brushing , with the intensity of stain , area of stain and number of sites with < 10 % stained tooth area , being recorded at each assessment . RESULTS Analysis of the results showed that the two electric toothbrushes were significantly better at removing stain than the manual toothbrush . In addition , the D9 was consistently more effective than the D7 , with the difference with respect to stain area achieving statistical significance ( P < 0.05 ) after 2 minute 's brushing . All three brushes were found to be safe , and there was no evidence of any soft or hard tissue abrasion . It was concluded that the oscillating/rotating electric toothbrushes were more effective in removing extrinsic dental stain than a manual brush , and that compared with the D7 , the newly design ed Braun Oral-B Ultra Plaque Remover has an increased potential for stain removal The efficacy and safety of a new sonic toothbrush were studied in this single-blind study . The sonic toothbrush combines acoustic vibrations and dynamic fluid activity surrounding the bristles with direct mechanical scrubbing of tooth surfaces . Fifty-one subjects were r and omly assigned to either the sonic or the manual toothbrush . Plaque scores were assessed before and after a 2-minute brushing at baseline and 1 , 2 , and 4 weeks . Gingivitis and sulcular bleeding scores were also taken at each evaluation . To assess long-term safety , 29 subjects returned after 6 months of product use . Repeated measures analysis of variance of the total mean plaque score indicated a significant difference between the devices over time ( P < 0.01 ) , with the sonic toothbrush demonstrating a greater level of plaque removal on all tooth surfaces . On average , the plaque reduction from the baseline score for the sonic toothbrush was 3 times greater than the manual brush . However , when broken down by dental region , the sonic toothbrush demonstrated an improved level of plaque removal ranging from 1.5 to 11.9 times better than the manual brush , with the greatest improvement in the interproximal and lingual areas . Both the gingivitis and sulcular bleeding scores exhibited a similar , significant reduction ( P < 0.005 ) over time for both devices with an approximate 17 % decrease in the gingivitis index and a 33 % decrease in sulcular bleeding sites . Safety assessment after 6 months of use indicated no soft tissue abnormalities which could be attributed to the products . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to evaluate the effect of brushing with both a sonic and mechanical counter rotary power toothbrush on the bond strength of orthodontic brackets . Forty-five extracted teeth were divided into three r and om groups and had orthodontic brackets bonded to them . One group was brushed with a counterrotational toothbrush , the Interplak , one group with a sonic toothbrush , the Sonicare , and a third group was not brushed and was held as a control . After the equivalent of 2 years brushing , the teeth were placed in an Instron machine and the shear force to remove the brackets was recorded . Group 1 , the counter rotary power brush , had a mean of 107.5 kg/cm2 , the second group , the sonic brush , had a mean of 79.7 kg/cm2 , and the control group had a mean of 125 . 4 kg/cm2 . Single factor analysis of variance followed by the Fisher-Hayter Multiple Comparison Procedure showed a statistically significant difference between the sonic power brush and the control ( P < .01 ) , but no significant difference between the counter rotary and the control ( P > .05 ) . There was no significant difference between the two power brushes ( P > .05 ) Removing plaque from interproximal areas is critical in preventing periodontal disease recurrence . Studies have shown the INTERPLAK counter-rotational powered brush is more proficient at this than conventional methods . To compare the effectiveness of the counter-rotational powered brush with conventional methods on midradicular and interproximal surfaces , periodontal surgery patients who were in supportive periodontal therapy were grouped into those using the counter-rotational powered brush device and those using conventional methods . Various measures of periodontal health indicated that over the 6-month study period , the counter-rotational powered brush result ed in a 40 % to 60 % improvement in clinical periodontal conditions compared with a 15 % to 40 % improvement with conventional methods A new sonic electric toothbrush ( Sonicare ) and a traditional manual toothbrush were compared for efficacy in removing supragingival plaque and reducing gingival inflammation in a 12-week , single-blind clinical trial . 60 subjects with a gingival index ( GI ) of > 1.5 and no probing depths > 5 mm were r and omly assigned to use either the manual or sonic brush , instructed in its use , and asked to brush each morning and evening for 2 minutes . Plaque scores were taken at baseline and at 1 , 2 , 4 , and 12 weeks using the Turesky modification of the Quigley-Hein plaque index . Gingival inflammation was assessed by the GI , bleeding tendency score , presence or absence of bleeding on probing , volumetric measurements of gingival crevicular fluid ( GCF ) , and aspartate aminotransferase ( AST ) levels in GCF . Repeated measures multivariate analyses of variance were used to detect time- and device-dependent differences for all clinical assessment s between the 2 groups over the 5 visits . Both types of brush were effective in removing supragingival plaque . The sonic brush was statistically superior , on a percentage reduction basis , in removing supragingival plaque from the dentition taken as a whole ( F-statistic ; p = 0.012 ) and was particularly better in hard-to-reach areas such as posterior teeth ( F-statistic ; p = 0.003 ) and interproximal sites ( F-statistic ; p = 0.004 ) . Both devices were equally effective in reducing gingival inflammation . The sonic brush exhibited less tendency to cause gingival abrasion than the manual brush ( 1 incident with sonic , 5 incidents with manual ) , confirming the safety of this product as an oral hygiene device Subgingival plaque removal at interproximal sites by automatic and h and toothbrushes was compared with control sites at which cleansing was not performed . There were 58 patients , 35 to 63 years of age , each with one hopeless tooth requiring extraction . Each patient was r and omly assigned to one of four test groups : h and brush ; automatic toothbrush 1 ; automatic toothbrush 2 ; and no brushing . The brushing instructions as stated by the manufacturers were demonstrated and the patient brushed the sextant containing the test tooth for 20 seconds . The level of the gingival margin was marked at each interproximal test site . The teeth were extracted and processed for SEM , and subgingival plaque was viewed at X100 and X2000 magnifications . A montage of photomicrographs of the gingival groove to the occlusal margin of the bacterial plaque at X100 magnification was made and the distance from the groove to the margin was measured . An ANOVA was performed using P = 0.05 level for significance . Due to processing difficulties , only 33 specimens were available for analysis . The average distances from the groove to the subgingival plaque front for the four test groups were 0.514 , 0.132 , 0.163 , and 0.111 mm respectively . The maximum distance ( 1.5 mm ) of plaque removal was greatest for the h and toothbrush . Due to the large st and ard deviation ( 0.636 compared to 0.146 , 0.250 , and 0.124 respectively ) , the h and brushing group was excluded from ANOVA . There were no statistically significant differences among the automatic toothbrushes and the no brushing control ( P = 0.8393 ) . It was concluded that a single session of oral hygiene instruction with an automatic toothbrush did not result in subgingival interproximal plaque cleansing OBJECTIVES The aim of the present study was to evaluate the efficacy of an electric toothbrush with a specially design ed orthodontic brush head compared with a manual toothbrush in controlling plaque and gingivitis in patients with fixed orthodontic appliances over an 8-week period in a dental practice setting . METHODS This was a r and omised controlled , single blind , stratified , parallel group trial conducted in two specialist orthodontic dental practice s by a specialist orthodontist . Group 1 comprised 41 subjects who used the electric toothbrush and Group 2 consisted of 43 subjects who brushed with a manual toothbrush around the orthodontic appliance for a timed 2 minutes twice daily for 8 weeks . Plaque around the fixed appliance attachments was measured using an orthodontic modification to the Silness and Loe plaque index , while gingival condition was scored using the gingival index and Eastman interdental bleeding index . RESULTS There was baseline balance for all clinical variables ( p > 0.05 ) . Both groups had significantly less plaque after 8 weeks than at baseline ( p < 0.001 ) but the group using the electric brush also had significantly less interdental gingival bleeding , as determined by the Eastman interdental bleeding index both at week 4 ( p < 0.001 ) and week 8 ( p = 0.004 ) . The majority of subjects ( n = 54 , 64.3 % ) preferred the electric toothbrush . CONCLUSIONS In conclusion , the results from this study would suggest that use of an electric toothbrush with an orthodontic brush head may be of benefit in promoting gingival health in fixed orthodontic appliance patients ; however , the long-term effects ( over at least 6 months ) need to be evaluated PURPOSE To compare the clinical efficacy with respect to plaque removal of a battery-operated power toothbrush ( Dr. Johns Spin Brush Classic ) with two manual toothbrushes , a st and ard ADA flat trim reference brush and the Oral-B CrossAction toothbrush . MATERIAL S AND METHODS Efficacy was evaluated in two independent studies using a r and omized , single-use , cross-over design . Healthy adult subjects from a general population brushed their teeth for a timed 1 min and plaque was scored before and after brushing was completed . In Study 1 ( Spin Brush vs. ADA toothbrush ) , plaque was scored using the modified Quigley and Hein Plaque Index , while in Study 2 ( Spin Brush vs. CrossAction ) plaque was scored using the Modified Navy Plaque Index . In addition , a hard and soft tissue examination was carried out before and after brushing to allow evaluation of safety . RESULTS In Study 1 , both the ADA toothbrush and the Spin Brush significantly reduced levels of whole mouth and approximal plaque ( P < 0.0005 ) ; however , the Spin Brush was not significantly more effective than the manual brush . Relative plaque reduction for the whole mouth was 35.6 + /- 16.0 % for the Spin Brush compared to 38.9 + /- 14.9 % for the manual toothbrush ( P < 0.047 ) , and , for the approximal surfaces , 32.7 + /- 14.6 % and 36.3 + /- 13.7 % , respectively ( P = 0.024 ) . In Study 2 , both toothbrushes significantly reduced plaque levels ( P < 0.0001 ) , but , as for Study 1 , the CrossAction manual toothbrush was more effective than the Spin Brush . For whole mouth , marginal and approximal sites , respectively , the Spin Brush reduced plaque by 54.3 % , 43.5 % and 62.0 % , compared with 58.6 % , 47.5 % and 67.1 % for the CrossAction toothbrush . The difference in favor of the CrossAction brush was statistically significant ( P < 0.0005 ) for all areas Adolescents with fixed orthodontic appliances frequently have increased levels of plaque accumulation and gingivitis . The purpose of this study was to determine whether a rotary electric toothbrush would be more effective than conventional toothbrushing in maintaining periodontal health in these patients . Forty adolescent patients were divided into equal groups matched for sex and age . Before and during placement of orthodontic appliances , one group was instructed in use of the rotary electric toothbrush and the other in the use of a conventional toothbrush ; these instructions were reinforced at monthly visits thereafter . Baseline clinical assessment s of Plaque Index , Gingival Index , and bleeding tendency were made on six st and ard teeth before appliances were placed . assessment s were repeated at 1 , 3 , 6 , 9 , 12 , and 18 months after appliances were placed . Intragroup and intergroup differences were tested by a two-way analysis of variance . At baseline there were no significant differences between the two groups for any study variable . During the 18-month study period , however , plaque accumulation and gingivitis increased significantly over baseline levels in the control group ( p less than 0.01 ) but remained stable in the group using the rotary electric toothbrush . In addition , the control group showed significantly greater plaque ( p less than 0.01 ) , gingival inflammation ( p less than 0.001 ) , and gingival bleeding on probing ( p less than 0.001 ) than did the treatment group from the 1- to 18-month examinations . These data suggest that the rotary electric toothbrush is more effective than conventional toothbrushes for removing plaque and controlling gingivitis in adolescents during orthodontic treatment with fixed appliances Fifty patients took part in a single blind study to test the plaque-removing efficacy of a new double-headed brush ( Duodent 2000 ) , compared with a conventional brush ( Oral B 32 ) . Twenty-seven patients were attending for an initial course of hygiene treatment , and 23 were recall patients with persistently inadequate plaque control . Plaque was assessed at baseline and at the end of the 2-week study period using the Turesky modification of the Quigley and Hine index for all buccal and lingual surfaces . All patients had plaque scores of more than 1 at baseline ( maximum = 5 ) . The reductions in mean plaque scores for combined lingual and palatal surfaces for subjects using the double-headed brush were significantly better than the corresponding reductions for the control groups . There were no significant differences between mean buccal plaque scores at the final examination for patients using either brush . The double-headed toothbrush helped to achieve better lingual and palatal plaque control , not only in the new patient group , but also in the group of patients who had not previously responded well to oral hygiene The aim of this study was to determine the plaque removing ability of a new toothbrush with a u-shaped head ( Superbrush ) compared to a conventional manual toothbrush ( Elmex ) and an electric toothbrush with a rotating head ( Braun Plak control ) . 36 healthy volunteers , aged 6 - 60 years , participated in this single blind cross-over study . They were r and omly assigned to 3 groups ( A , B , C ) with 12 participants each . To obtain a plaque-free condition at the baseline , professional toothcleaning was performed in each participant . After instructions on how to use the toothbrushes , each group started the experiment with a different type of toothbrush . After 1 week of application , the Quigley-Hein plaque index ( QHI ) and the proximal plaque index ( API ) were used to assess the oral hygiene status of each participant . This was followed by 1 week of recess before each group switched to the next type of toothbrush . The duration of the study was 5 weeks . All examinations were performed by 1 examiner . Compared to the 2 other brushes , the Superbrush was more effective in removing plaque ( medians of QHI : 0.84 versus 1.56 ( Elmex ) and 1.56 ( Braun ) ; p<0.001 ; medians of API : 0.69 versus 0.94 ( Elmex ) and 0.87 ( Braun ) ; p<0.001 ) . The study indicated that the new toothbrush may be an effective alternative to commonly used toothbrushes Twenty-one patients with rheumatoid arthritis took part in a comparison of three toothbrushes , each used for one month in a r and omized trial . The three toothbrushes were a conventional toothbrush with modified h and le to allow ease of gripping , an electric toothbrush , and thirdly a finger-stall attached to a normal toothbrush . There was no change in the patients ' rheumatoid status during the trial . The patients were scored for plaque and gingival changes but no difference was found between the three toothbrushes . We recommend a st and ard toothbrush with a modified grip for the rheumatoid h and ; the extra expense of an electric toothbrush can not be justified PURPOSE To compare the efficacy and safety of a novel electric toothbrush ( Braun Oral-B 3D Plaque Remover ) with a st and ard reference ADA manual toothbrush . MATERIAL S AND METHODS 114 subjects were included in a 3-month r and omized , parallel group , examiner-blind study and divided into two groups : 3D users and manual toothbrush users . Subjects were instructed to brush twice daily for 2 minutes . Evaluation of oral soft and hard tissue for safety , plaque , gingivitis and bleeding was conducted prior to the start of product use ( at baseline ) , at days 14 and 35 , and at 3 months . RESULTS 105 subjects ( 55 3D users and 50 manual toothbrush users ) completed the study . At days 14 , 35 and at 3 months both groups showed reductions from baseline in whole mouth plaque , gingivitis and bleeding that were statistically significant ( P < 0.005 ) , except in the case of plaque at day 35 in manual toothbrush users . At 3 months , reductions for whole mouth plaque , gingivitis and bleeding were 15 % , 16 % and 65 % , for 3D users and 8 % , 12 % and 56 % , for manual toothbrush users , respectively . Group differences were significant ( P < 0.05 ) in favor of the 3D with respect to plaque reduction for the whole mouth and for interproximal and anterior lingual sites at all three time periods . With respect to gingivitis , reductions for the whole mouth and interproximal and posterior lingual sites at 3 months were significantly greater in the 3D group . There was no clinical ly significant soft or hard tissue abrasion in either group . In conclusion , the 3D electric toothbrush was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis compared to a manual toothbrush BACKGROUND / AIM The purpose of the present investigation was to compare manual ( Crest Complete ) and powered toothbrushing ( Braun Oral-B 3D Plaque Remover ) for their ability to affect clinical parameters of periodontal diseases . METHODS 48 periodontal maintenance subjects completed this single-blind 6-month longitudinal study . Subjects had a minimum of 20 natural teeth excluding third molars and > 10 % of sites ( approximately 17 sites ) with pocket depth > or = 4 mm and /or > 10 % sites with attachment level > 4 mm . At baseline , subjects received full mouth clinical measurements ( 168 sites ) to determine mean Plaque Index , Gingival Index , pocket depth and attachment level and % of sites exhibiting BOP . Subjects were then r and omly assigned to one of two groups . The control group ( N=26 ) used a manual toothbrush while the test group ( N=22 ) used a powered toothbrush . Subjects received instruction in oral hygiene and used their assigned toothbrush twice daily according to instruction . Follow-up clinical assessment s were performed at 3 and 6 months . Significance of differences in clinical measures over time was determined using the Quade test and between brushing groups at each time point using the Mann-Whitney test . RESULTS Mean pocket depth , mean plaque index and % of sites exhibiting BOP showed significant reductions from baseline to 3 and 6 months in both groups . Mean probing attachment level and mean Gingival Index were significantly reduced in the powered brushing group only . There was a significant positive correlation between plaque reduction and reduction in other clinical parameters in both brushing groups . The majority of subjects showed improvements in clinical parameters at 6 months , although a greater proportion of subjects in the powered group showed a reduction in Plaque Index ( 77 % versus 65 % ) and in % sites exhibiting BOP ( 82 % versus 69 % ) . Mean pocket depth and mean attachment level showed significantly greater reductions between baseline and 6 months in lingual and m and ibular areas in the powered group . CONCLUSIONS Both manual and powered toothbrushes reduced pocket depth , plaque index and BOP . The powered toothbrush significantly reduced mean gingival index and probing attachment level . The greatest benefit of the powered brush was at m and ibular and lingual surfaces BACKGROUND Prophylaxis efforts for the maintenance of tooth health led to a distinctive decrease in caries frequency with children and young persons . Because the toothbrush can still be described as the most important oral hygiene aid , possible differences between the effectivity of electric and manual toothbrushes should be tested in the present study . Elementary school children had been instructed -- within a special prophylaxis program -- over a period of three years to clean their teeth partly with electric partly with manual toothbrushes . MATERIAL AND METHODS In two parallel classes ( 1st class ) of the same elementary school ( Private Martinusschule Mainz-Gonsenheim ) the A-class ( n = 24 children ) was instructed to clean their teeth with a manual toothbrush suitable for children ( Oral-B , Power Tip , Braun AG , Kronberg , Germany ) whereas the B-class ( n = 26 ) received electric toothbrushes ( Oral-B-7 EB 5 K , Braun AG , Kronberg , Germany ) . Every three months the children were instructed in group-preventive methods in school , followed by cleaning instructions , remotivations and the distribution of new electric respectively manual toothbrushes . In order to record the influence of the intensive quarterly oral hygiene instruction , elementary school children ( 1st class ) of the same school type were looked after and examined within the yearly group prophylaxis ( n = 40 ) . The yearly dental examinations included the recording of carious frequency ( DMF-T , dmf-t ) , approximal plaque accumulation ( API ) , and the evaluation of the gingival state ( GI-Index ) as well as the present dental restorative material s. RESULTS After an investigation period of three years no essential differences regarding caries frequency , proportion of dentitions of natural state of health and plaque involvement were found with the children of the respective classes . Children using electric toothbrushes showed after 3 years 27 % of healthy-natured dentitions on average ( 46 % of the children had got API-values of up to 30 % ) and the children who used manual toothbrushes showed 22 % of nature-healthy dentitions ( 52 % of the children had got API-values of up to 30 % ) and in 33 % of the control children who received instructions only once a year healthy-natured dentitions were found after 3 years ( 75 % of the children had got API-values of up to 35 % ) . CONCLUSIONS With regard to caries and gingivitis prevalence modern electric toothbrushes for children can be considered equally efficient like conventional manual toothbrushes for children with children of normal caries risk A blind , two-way crossover clinical trial was carried out to compare the effectiveness of plaque removal between an electric toothbrush ( Interplak ) and a conventional manual toothbrush ( Butler 311 ) . Twenty adult patients having completed all active periodontal therapy and currently on periodontal maintenance program participated in the study . Each toothbrush was used for a period of 2 weeks by all subjects . The mean differences between baseline plaque scores and after the subjects used the brushes were analyzed by the paired t-test . The results indicated no difference in plaque removal between the Interplak and the control brush with the exception of the distal surfaces of the maxillary teeth A cross-over , single-blind clinical study was performed to compare a powered and a manual toothbrush for their ability to remove plaque from the teeth of pre-school children . Seventy-three r and omly selected 4- to 6-year-old children from two kindergarten classes in Erfurt , Germany participated in the study . A new powered children 's toothbrush ( Rowenta ) and a currently marketed manual children 's toothbrush ( Elmex ) were used for an assessment period of two weeks each . Then the groups were crossed over to use the alternate toothbrush for another two weeks . Whole mouth , gingival margin and interproximal plaque area levels were determined using the Rustogi et al. plaque index . Statistical analysis of the data showed significantly effective ( p < 0.05 ) plaque removal with both toothbrushes , immediately after toothbrushing and at one and two weeks , compared to the respective baseline scores . The statistical analysis also demonstrated that the powered toothbrush was significantly ( p < 0.05 ) better on percent plaque reduction on all tooth areas compared to the manual toothbrush , except at two weeks with the interproximal assessment The objective of this 30-day clinical study , conducted in harmony with American Dental Association guidelines , was to evaluate the efficacy of a new battery-powered toothbrush ( Colgate Actibrush ) relative to a manual toothbrush ( Colgate Plus Diamond Head Toothbrush , Full Head , Soft Bristle ) in the control of supragingival plaque and gingivitis . A total of 110 adult men and women from the Northern New Jersey area were entered into the study and stratified into 2 balanced groups according to baseline plaque and gingivitis scores . Participants were instructed to brush twice daily ( morning and evening ) for 1 minute with their assigned toothbrush and a commercially available toothpaste ( Colgate Cavity Protection Great Regular Flavor Fluoride Toothpaste ) . Examinations for plaque and gingivitis were conducted by the same dental examiner at baseline , after 15 days , and again after 30 days of product use . All 110 participants complied with the protocol and completed the 30-day clinical study . At the 30-day examinations , the group using the Colgate Actibrush battery-powered toothbrush exhibited a statistically significant greater reduction in plaque ( 26.7 % ) and in gingivitis ( 25.8 % ) than did the group who used the Colgate Plus Diamond Head Toothbrush . The results of this 30-day clinical study support the conclusion that the Colgate Actibrush battery-powered toothbrush provides a clinical ly superior level of efficacy for the control of supragingival plaque and for the control of gingivitis when compared with a manual toothbrush There have previously been no studies on the cost effectiveness of the use of a counter-rotational toothbrush ( INTERPLAK Home Plaque-Removal Instrument ) , which has been demonstrated to be more effective than ordinary toothbrushes in reaching plaque-removal and gingival-health goals . Killoy et al studied the costs of required periodontal treatment for 32 patients with moderate periodontitis at two corporate capitation dental centers . The subjects were divided into two groups , a test group that brushed with a counter-rotational toothbrush and one that brushed with a manual toothbrush . Probing depth , attachment levels , and plaque and bleeding indexes in the test brush group were better than those in the control group . The end result was a mean reduction of $ 535 in the cost of periodontal treatment that had been planned before using the counter-rotational brush over 18 months , while the group using the manual brush experienced a mean increase of $ 11 in required treatment over original plans . Furthermore , the test group reached a state of gingival health , but the control group did not . The study concluded that the counter-rotational brush is cost effective A double-blind clinical study was conducted to compare the plaque-removing efficiency of a newly design ed electronic toothbrush to that of a placebo , conventional toothbrush . Twenty-six students were selected at Asahi University , School of Dentistry in Japan . The subjects were divided into two groups , one which used the electronic toothbrush and the other which used the placebo toothbrush . The subjects served as their own control by brushing manually for 3 minutes . The plaque elimination ratio , however , showed no significant difference between the testing and the control group . The main conclusion of this study is that an electronic toothbrush is not superior to the conventional toothbrush BACKGROUND Subjects with high plaque and gingivitis scores can profit most from the introduction of new manual or powered tooth brushes . To improve their hygiene , not only the technical characteristics of new brushes but also the learning effect in efficient h and ling are of importance . AIM : The present study compared the efficacy in plaque removal of an electric and a manual toothbrush in a general population and analysed the learning effect in efficient h and ling . METHOD Eighty healthy subjects , unfamiliar with electric brushes , were divided into two groups : group 1 used the Philips/Jordan HP 735 powered brush and group 2 used a manual brush , Oral-B40 + . Plaque index ( PI ) and gingival bleeding index ( GBI ) were assessed at baseline and at weeks 3 , 6 , 12 and 18 . After each evaluation , patients abstained from oral hygiene for 24 h. The next day a 3-min supervised brushing was performed . Before and after this brushing , PI was assessed for the estimation of the individual learning effect . The study was single blinded . RESULTS Over the 18-week period , PI reduced gradually and statistically significantly ( p<0.001 ) in group 1 from 2.9 ( + /-0.38 ) to 1.5 ( + /-0.24 ) and in group 2 from 2.9 ( + /-0.34 ) to 2.2 ( + /-0.23 ) . From week 3 onwards , the difference between groups was statistically significant ( p<0.001 ) . The bleeding index decreased in group 1 from 28 % ( + /-17 % ) to 7 % ( + /-5 % ) ( p<0.001 ) and in group 2 from 30 % ( + /-12 % ) to 12 % ( + /-6 % ) ( p<0.001 ) . The difference between groups was statistically significant ( p<0.001 ) from week 6 onwards . The learning effect , expressed as the percentage of plaque reduction after 3 min of supervised brushing , was 33 % for group 1 and 26 % for group 2 at week 0 . This percentage increased at week 18 to 64 % in group 1 and 44 % in group 2 ( difference between groups statistically significant : p<0.001 ) . CONCLUSION The powered brush was significantly more efficient in removing plaque and improving gingival health than the manual brush in the group of subjects unfamiliar with electric brushes . There was also a significant learning effect that was more pronounced with the electric toothbrush BACKGROUND Individuals purchasing electric toothbrushes for the 1st time will mostly only have the manufacturer 's instructional leaflet for information of usage . AIMS This study was design ed to simulate the 1st-time purchase and early use of an electric toothbrush with the aim of comparing plaque removal with a manual toothbrush . Secondary aims were to assess chemical plaque removal effects of a toothpaste slurry and to compare between 2 electric brushes which differed only in head speed . METHODS A group of 16 dentate subjects participated in this single-examiner blind , r and omised , crossover design balanced for residual effects . Subjects had " average " oral hygiene and had never used an electric toothbrush previously . 7 days prior to the study , all subjects received the slower oscillating rotating toothbrush under test to use at home as they wished . The test treatments were brushing with 2 oscillating rotating electric toothbrushes , a manual toothbrush and a rinse with a toothpaste slurry ( 3 g/10 ml water ) . On day 1 of each study period , subjects were rendered plaque-free , suspended oral hygiene and returned on day 5 . Plaque was scored at baseline by index and area and after 30 s , 30 s ( total 60 s ) and 60 s ( total 120 s ) of the cleaning treatments . Washout periods were at least 2 1/2 days . RESULTS Highly significant treatment differences were found between the 4 treatments because the toothpaste slurry was totally without effect . Analyses between the 3 brush treatments overall revealed no consistent significant differences . The data suggest that in the early days of electric toothbrush use , subjects perform no better than using a manual brush . CONCLUSIONS The present study , taken with results from others showing greater benefits from the use of electric brushes , supports the idea that dental professionals should , where possible , provide advice and instruction in the use of such devices PURPOSE To compare the efficiency of a new electric toothbrush featuring a novel three-dimensional brush head action , with a manual toothbrush , in resolving gingivitis which had been allowed to develop in a group of subjects prior to the treatment phase of the study . MATERIAL S AND METHODS This was a r and omized split-mouth study . A total of 35 healthy non-dental students refrained from any oral hygiene on the lower jaw for a period of 21 days in order to develop gingivitis . They then brushed one quadrant of the lower jaw with the Braun Oral-B 3D Plaque Remover and the other with a manual toothbrush for a period of 4 weeks . Plaque and gingivitis were evaluated at the start of the study , after the 21 days of no oral hygiene , and after 1 , 2 , 3 and 4 weeks of brushing twice a day . RESULTS At the end of the study , the 3D was found to be significantly more effective at reducing bleeding on probing ( P < 0.05 ) for all sites combined and all individual sites . Plaque removal was also significantly more effective with the 3D . Subjects in the study reported that they preferred the 3D to the manual toothbrush and said that it would encourage them to brush for longer . It is concluded that the new Braun Oral-B 3D Plaque Remover offers advantages over a manual toothbrush in terms of plaque control and improvement of gingival condition PURPOSE To compare the safety and efficacy of a manual toothbrush and a battery-operated power toothbrush in two separate studies , one utilizing a single-use design and the other a 3-month parallel-group design . MATERIAL S AND METHODS The toothbrushes compared in the two studies were the Oral-B CrossAction manual toothbrush and the Colgate Actibrush battery-operated power toothbrush . The single-use study , which used a single-blind , cross-over design , involved 71 healthy subjects , who were instructed to abstain from oral hygiene for 23 - 25 hours prior to brushing with each of the two toothbrushes . Plaque was measured using the Proximal Marginal Index ( PMI ) pre- and post-brushing . The 3-month parallel-group study involved a total of 113 subjects who had plaque ( PMI ) , gingivitis and bleeding ( Loe and Silness ) scored at baseline and after 1 and 3 months of product use . RESULTS In both studies , the two toothbrushes were found to be safe . In the single-use study , significantly greater amounts of plaque were removed by the CrossAction manual toothbrush than by the Actibrush for the whole mouth as well as for marginal and approximal sites ( P < 0.001 ) . In the 3-month study , significantly greater plaque reduction was achieved with the CrossAction brush , the advantage being significant at 1 month for all sites except lingual sites ( P < 0.05 ) . At 3 months , there were consistent numerical advantages in favor of the CrossAction at all sites except lingual sites . Reductions in gingivitis were found to be similar with both toothbrushes The purpose of the present study was to test the effectiveness of a new type of BRAUN electric toothbrush ( D5 ) in comparison with the traditional BRAUN electric toothbrush ( D3 ) and to a manual toothbrush ( M ) . For this study , 60 dental students were selected who had no previous experience with the use of an electric toothbrush . The study consisted of 3 experiments . Prior to each experiment , all students were asked to abstain from all oral hygiene procedures for at least 24 h. In Exp I , the efficacy of toothbrushing was studied when one of the investigators brushed the teeth of the students . No toothpaste was used in this first part of the study . In Exp II , the efficacy of brushing was evaluated when the brushing was carried out by the students themselves . In Exp III , the efficacy of the brushing was studied after the students had received a professional instruction and oral prophylaxis . The available time for the brushing amounted to a total of 2 min per mouth . The amount of dental plaque was evaluated by means of the Silness and Löe plaque index at 6 sites around the tooth . Results showed in Exp I that both electric toothbrushes proved to remove significantly more plaque than the manual toothbrush ( M 78 % ; D3 85 % ; D5 86 % ) . In Exp II , no significant differences in plaque-removing efficacy were found between the 3 brushes ( M 73 % ; D3 72 % ; D5 73 % ) . In Exp III , the D5 proved to remove significantly more plaque than the other two brushes ( M 77 % ; D3 77 % ; D5 83 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS Plaque removal is an important part of good oral hygiene . Many short-term studies have compared the effectiveness of an electric toothbrush in plaque removal to that of a conventional , manual toothbrush . Previous studies proved the electric toothbrush to be more effective on a short-term basis ; however , little is known about its long-term effects . In a study that examined 32 patients over a 12-month period , the authors found electric toothbrushing to be more effective in plaque removal . The study measured the differences in abrasion , gingival recession , gingival bleeding , and plaque scores . The study also concluded that no significant gingival abrasion was caused by electric toothbrushing OBJECTIVES The study was design ed to test the efficacy in plaque removal of three toothbrushes : two manual brushes , the Butler GUM 311 and the Dr Best X-Active , and one electric toothbrush the Braun Oral-B 3D Plaque Remover ( 3D ) . METHOD The study was a split-mouth , single-blind , r and omized clinical study consisting of three identical experiments testing three combinations of toothbrushes ( experiment 1 : 3D versus Butler ; experiment 2 : 3D versus Dr Best ; experiment 3 : Butler versus Dr Best ) , in which the teeth of the panellists were brushed by a dental hygienist . In a fourth experiment , the panellists brushed their own teeth ( 3D versus Dr Best ) . Thirty-five subjects participated in the study and received a professional prophylaxis prior to the first experiment . They were requested to refrain from brushing their teeth for 48 h prior to each experiment . Plaque was assessed according to the Silness & Löe plaque index at six sites per tooth . Next , the dental hygienist ( experiments 1 - 3 ) or the panellist ( experiment 4 ) brushed for 60 s with their first assigned brush in two r and omly selected contralateral quadrants . Brushing was repeated ( 60 s ) with the second brush in the opposing two contralateral quadrants . Prior to experiment 4 , panellists were given two thorough h and s-on professional instructions in the use of the 3D and the Dr Best toothbrushes . RESULTS In experiment 1 , the 3D showed a mean plaque reduction of 72 % compared to 63 % with the Butler ( P<0.01 ) . In experiment 2 , the 3D showed a mean plaque reduction of 79 % and the Dr Best 76 % ( P<0.05 ) . In experiment 3 , the Butler showed a mean plaque reduction of 81 % and the Dr Best 85 % ( P=0.01 ) . In the h and s of the panellists ( experiment 4 ) , the 3D showed a mean plaque reduction of 88 % and the Dr Best 84 % ( P<0.05 ) . CONCLUSIONS A 5-week training period with repeated h and s-on instruction gives panellists the skill to perform brushing with efficacy comparable to that of professional brushing . In agreement with a previous study , the 3D was more effective than a flat-trimmed manual toothbrush ( Van der Weijden et al. 1994 ) . Brushing with the criss-cross result ed in small statistical differences with the 3D and the flat-trimmed manual toothbrush . The clinical relevance of these statistically significant results should be the subject of a longitudinal study Although a high level of oral cleanliness is essential for long-term maintenance of dental health , many people can not maintain good oral hygiene consistently . A new electronic toothbrush has been developed that induces a small electric charge onto tooth surfaces . This charge damages electrostatic bonding of plaque proteins to tooth surfaces ; thus , plaque removal is enhanced while the toothbrush is used . Young men were issued identical toothbrushes ; some were electrically active . Plaque levels were assessed at baseline , and after two and four weeks , concurrently with oral-hygiene instruction and professional prophylaxis . The electrically active toothbrushes demonstrated better plaque removal than the inactive toothbrushes . This better performance was statistically significant linguopalatally , indicating that significantly more plaque was removed where mechanical access was poorest . Thus , the electrical activity of this toothbrush significantly enhances plaque removal where toothbrushing access is limited BACKGROUND The aim of this study was to determine the plaque-removing ability of a curved bristle toothbrush compared to a conventional , straight bristle , manual toothbrush . METHODS The study group consisted of 100 volunteers 16 to 24 years of age from a professional engineering college . A four-week post-prophylaxis , parallel , longitudinal , double-blind clinical study was conducted ; all volunteers were instructed in specific oral hygiene techniques . Plaque was assessed at baseline and at the end of 1 , 2 , 3 , and 4 weeks using the Quigley-Hein plaque index after disclosing with erythrosin red . Gingival status was assessed at baseline and at the end of 1 , 2 , 3 and 4 weeks by using the gingival index of Löe and Silness . RESULTS Comparative assessment showed a mean of 2.11 + /- 0.086 mm for group 1 and 2.37 + /- 0.216 mm for group 2 , indicating a significant difference between the plaque-removing efficacy of the curved bristle and straight bristle toothbrush . CONCLUSIONS The curved bristle toothbrush was significantly more effective in removing plaque overall than the conventional toothbrush This single ( examiner ) blind , r and omized , 4-week study compared the safety and efficacy of a new electric toothbrush ( experimental ) regarding plaque removal and reducing gingivitis with two other brushes , an electric brush ( control electric ) and a manual toothbrush ( control h and ) . Ninety-six subjects with 1 ) a minimum of 15 suitable teeth in acceptable occlusion ; 2 ) a minimum gingivitis score of 0.9 ; and 3 ) a minimum plaque score of 1.8 were entered into the study . The subjects were r and omly assigned to one of 3 groups : a control h and group ( 31 subjects ) , an experimental group ( 32 subjects ) , and a control electric group ( 33 subjects ) . Device use instructions were given according to the manufacturer 's recommendations . Two examiners separately determined either gingival scores or plaque scores at baseline and 4 weeks . In regard to gingivitis , use of all 3 brushes for the study period showed statistically significant improvements in gingivitis scores ( P values less than 0.01 ) within each of the 3 groups . Between group analyses of covariance showed that of the 3 groups , the control h and group improvement was better than both the experimental and the control electric groups ( P less than 0.05 ) . When interproximal gingivitis scores were analyzed separately , similar improvements were noted . Regarding effectiveness of plaque removal during a single brushing event at the initial and final visits , each of the 3 brushes was effective in reducing plaque for every tooth surface scored ( P values less than 0.01 ) . However , between group analyses of covariances showed that the experimental group was better than the other two ( P less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS A clinical study was carried out in an attempt to assess the efficacy of a newly design ed electric toothbrush compared to a conventional manual toothbrush using the American Dental Association 's protocol for evaluating toothbrushes . An Oral-B 35 manual toothbrush , which served as the control , was compared to the Plaq & White125 electric toothbrush . Examinations were performed by two calibrated examiners at baseline , day 15 and day 30 . Examinations included the gingival index , plaque index and bleeding index . Mean indices were calculated and compared between the two brushes using the repeated measures multiple analysis of variance . No statistically significant differences between the mean indices on the three examination days were observed following the use of the manual or the electric toothbrushes . The results of this study demonstrate that the electric toothbrush was numerically more effective than the manual toothbrush in reducing supragingival plaque levels , either before or after brushing , at each examination date compared to baseline plaque values . However , this difference was not statistically significant . This and other findings concluded that the Plaq & White toothbrush is comparable to the control ADA-accepted toothbrush Two long-term studies were conducted to evaluate the therapeutic efficacy of five manual toothbrushes compared to the Oral-B Advantage Plaque Remover measuring plaque removal and gingivitis/bleeding reduction . Both studies were carried out under the same protocol and utilized the same examiners . In Study 1 , the Oral-B Advantage Plaque Remover was compared to the Crest Complete and Colgate Precision toothbrushes . In Study 2 , the Oral-B Advantage Plaque Remover was compared to the Reach Advanced Design , Colgate Plus and Jordan Exact toothbrushes . A total of 109 and 121 male and female subjects who met the inclusion and exclusion criteria completed Study 1 and Study 2 , respectively . Subjects were initially screened for dental plaque eligibility having abstained from oral hygiene for a prior 24-hour period . Subjects were r and omly assigned to one of the balanced groups and received a professional prophylaxis to reduce plaque scores . Subjects were then scheduled to return 4 weeks and 8 weeks later , having again abstained from all oral hygiene procedures for a prior period of 24 hours . At each visit , each subject was evaluated for plaque , gingivitis and bleeding . Upon completion of the study , the data were subjected to statistical analysis . The results of both studies are summarized as follows : The Oral-B Advantage Plaque Remover was significantly more effective than the Crest Complete , Colgate Precision , Colgate Plus and Jordan Exact toothbrushes in whole mouth plaque removal ( p < 0.05 ) , and vs. all brushes tested in gingivitis reduction ( p < 0.01 ) and in reducing gingival bleeding ( p < 0.001 ) BACKGROUND / AIMS The principal aim of the study was to compare the efficacy of a powered toothbrush ( PTB ) prototype ( B ) brush head in removing dental plaque to the relative efficacy of a marketed model ( A ) . METHOD A 12-week , 2-group , 2-treatment , double-blind trial of 2 , two-brush heads ( with the same power unit ) recruited 62 volunteers ( 18 - 25 years ) who were non- clinical university students . After a screening visit , 31 subjects were allocated to each of groups A and B at baseline with stratification according to gender and plaque index . After 48 h of plaque growth , subjects underwent a timed and supervised brushing episode with the allocated PTB ( visit 1 ) . Subjects then used the PTBs at home for 12 days before being recalled ( visit 2 ) and asked again to abstain from all oral hygiene measures for 48 h. Supervised brushing was repeated ( visit 3 ) before the subjects were dismissed for a further 10-week , unsupervised period of home use of the PTBs . The sequence of visits ( 2 and 3 ) was then repeated at visits 4 and 5 . RESULTS The sole outcome variable was plaque which was scored at all visits using the modified Quigley & Hein Index ( PI ) at full mouth ( FM ) , interproximal ( IP ) and smooth surfaces ( S ) . At visits 1 , 3 and 5 , the PI was recorded both before and after supervised brushing . There were no significant differences in PI between the brushing groups at baseline , visit 1 , visit 2 or visit 5 ( 2 sided t-test ) . At visit 3 , the prototype achieved significantly lower PIs than the marketed PTB brush head for IP ( and FM ) surfaces , this difference was most apparent on posterior tooth surfaces . For within-group changes , PIs at visit 2 were significantly lower than those at baseline ( paired t-test ) , an observation which may be attributable to the improved cleaning and ' novelty effect ' of a PTB . The PIs at visit 5 were significantly higher than the baseline values ( paired t test ) and this may be accountable to an element of Hawthorne effect and /or , a fall off in compliance over the entire 12 weeks . CONCLUSION We conclude that this in vivo model is appropriate for testing the efficacy of PTB prototypes but only over a 2-week period , as the inter-group differences were not maintained over the full 12 weeks of the trial The aim of this 3-group , 3-treatment , single-blind , parallel group study was to evaluate and compare the efficacies of the Philips/Jordan HP 735 powered toothbrush , the Braun/Oral B D7 powered toothbrush and the Oral B Advantage B35 manual toothbrush in a cohort of 75 young adults ( 18 - 25 years ) . Following an appointment for screening , full mouth mean ( + /-sd ) modified Turesky plaque index ( PI ) and Löe & Silness gingival index ( GI ) were recorded at baseline . After 24 h abstinence from all oral hygiene measures , PI was recorded and each subject was given one of the test brushes with detailed instructions for use . The subject then brushed under supervision for 90 s , during which time mean ( + /-sd ) toothbrushing forces ( TBF ) were recorded . PI were recorded immediately after supervised brushing and the subjects were then discharged for 6 weeks to use the allocated toothbrush at home . After 6 weeks , PI , GI and TBF were again recorded . Comparisons between the brushing groups for all parameters , at baseline , 24 h and 6 weeks were tested using ANCOVA . There were no significant differences for PI and GI between groups at baseline , or for PI following supervised brushing at 24 h. After 6 weeks subjects using the powered brushes had lower mean PI ( + /-sd ) scores than those using manual brushes but the differences were significant only at interproximal sites ; HP 735 1.44 ( 0.52 ) , D7 1.44 ( 0.53 ) , B35 1.75 ( 0.51 ) ( p=0.05 ) . At 6 weeks , mean ( + /-sd ) GI were ; HP 735 1.49 ( 0.21 ) , D7 1.61 ( 0.21 ) , B35 1.64 ( 0.22 ) ( p=0.033 ) . Mean GI scores for the HP 735 group were similar at baseline and at 6 weeks although for the other brushes , the GI scores actually increased over this period . Mean ( + /-sd ) TBF ( grammes/force ) at baseline and 6 weeks respectively for the brushes were ; HP 735 233 ( 205 ) , D7 159 ( 58 ) , B35 279 ( 122 ) ( p=0.026 ) : HP 735 194 ( 86 ) , D7 141 ( 57 ) , B35 297 ( 113 ) ( p=0.0001 ) . The within-group variability for the HP 735 TBF reduced considerably over 6 weeks , a likely consequence of the click-force threshold feature of this brush Three separate studies have been conducted to evaluate the clinical safety and efficacy of the Plak Trac mechanical toothbrush . In an exaggerated use study , volunteers used the product a minimum of five times a day for eight days . Soft tissue evaluations were conducted before and at various times after use of the Plak Trac brush throughout the study . No tissue irritation related to product use was observed or reported at any time in the study . In a thirty-day at-home use study the Plak Track brush was compared to the Colgate ADA-approved manual toothbrush . Plak Trac was consistently more effective than the Colgate brush on plaque removal , at higher statistical levels . Both brushes were effective in decreasing the gingival index during the study . In a one-time use test , Plak Trac , Interplak , and the Oral B 35 manual brush were evaluated for plaque removal efficacy . All brushes significantly reduced both smooth surface and interproximal plaque scores . On total smooth surfaces Plak Trac was significantly more effective than the Interplak brush The influence on plaque-removing efficiency of the alternating frequency of a powered brush has never been established . In the present study , a mechanical brush was tested at various alternations per minute ( F1 = 2100 , F2 = 2500 , F3 = 3500 ) . A double-blind , r and omized , triple crossover design was applied . After a plaque growth phase , the test brushes were used under supervision for 90 s and the remaining plaque scored . A ridit analysis yielded significant differences between F2 and F1/F3 . Odds ratios and frequency distributions demonstrated a clinical ly meaningful advantage for F2 . Subjective evaluation by the participants confirmed the positive performance of F2 . The results can be generalized in 3 ways : ( 1 ) the alternating frequency of a power brush influences its effectiveness , ( 2 ) high frequencies are not generally superior , ( 3 ) the test brush has its optimal cleaning efficiency at F2 , which does not necessarily need to be true for other br and s. It seems imperative to determine the optimal frequency for any new brush in a controlled study A clinical trial was design ed to test the relative numbers of gingival lesions caused during st and ardized brushing of the teeth of 22 volunteer dental nurse students with a manual soft multitufted , a manual soft V-shaped , and an electric toothbrush . First , the left or the right side of the jaws of each subject was brushed by a dental hygienist using the manual V-shaped or the electric brush , and the other side using the manual multitufted brush . At the 2nd brushing 1 week later , the same hygienist used the multitufted brush for brushing the side contralateral to the one in which it was used the 1st week and the V-shaped manual brush instead of the electric and vice versa . After each brushing , the number of new gingival lesions was recorded and the cleansing effect evaluated by assessment of the amount of remaining plaque . This examiner was unaware of the type of brush used . The V-shaped manual toothbrush was found to have caused more gingival abrasion than the electric toothbrush ( P less than 0.005 ) and a similar difference was found between the multitufted manual and the electric toothbrush ( P less than 0.05 ) . There was no clinical ly significant difference between the plaque removing effects of the 3 brushes tested The aims of the present study were : ( 1 ) to establish the incidence of gingival abrasion as a result of toothbrushing , using a manual and electric toothbrush ; ( 2 ) to establish the influence of filament end-rounding on the incidence of gingival abrasion and the efficacy of toothbrushing ; ( 3 ) to assess whether the speed of the electric brush has a feedback-effect on the brushing force used and to correlate the incidence of gingival abrasion with force . 2 experiments were carried out . In the first experiment , 50 subjects brushed for 3 weeks every other day with either a manual ( Butler 411 ) or an electric toothbrush ( Braun/Oral-B Ultra Plaque Remover-D9 ) . All received brief instructions and were asked to abstain from oral hygiene 24 hrs before their appointment . After disclosing the teeth and gums with Mira-2-Tone solution , plaque and gingival abrasion were assessed . Next , the panelists brushed in a r and om split-mouth order . After brushing and a second disclosing , plaque and abrasion were re-assessed . The results showed that the incidence of gingival abrasion was comparable for the manual and the D9 . Using a similar design as in experiment no. 1 , in experiment no. 2 a new group of 47 subjects brushed for 3 weeks alternating between the Braun/Oral-B Plaque Remover-D7 and D9 . At the appointment , the subjects first brushed in a split-mouth order with the D9 with 2 different types of endrounding . Plaque and abrasion were assessed . Immediately following this brushing exercise , the subjects re-brushed with the D7 ( 2800 rot/min ) and the D9 ( 3600 rot/min ) during which brushing force was measured . The results of this experiment showed that endrounding has no effect on plaque removal but does effect the incidence of gingival abrasion . Brushing force is not influenced by the speed of the brushhead and no correlation with the incidence of gingival abrasion was observed . In conclusion , the results of this study show that gingival abrasion is not influenced by brushing force , but is affected by filament endrounding The purpose of the study was to compare the efficacy of two electric toothbrushes ( Philips HP555 and the Philips Jordan 2-action Plaque Remover HP510 ) . A manual toothbrush ( Jordan V-shaped , medium ) served as control . Fifty subjects , aged 18±60 years , participated in a r and omized , single-blind , 3 x 3 weeks crossover study . Plaque was assessed according to the Turesky modification of the Quigley-Hein index ( P.I. ) , while the Løe-Silness index was used for assessing gingivitis . Adverse effects were assessed according to the ADA specifications . Compliance and preference were assessed through question naires and interviews , respectively . All periods mean P.I. ( all surfaces ) were 2.79 , 3.01 , and 2.86 for the manual , the HP555 , and the HP510 electric brushes and the corresponding gingivitis values were 1.19 , 1.22 , and 1.21 . For both indices , only the difference between the manual and the HP555 yielded significance ( P = 0.04 and P = 0.02 ) . Most subjects ( 28/50 ) preferred the HP510 brush , as it felt more practical to use and was perceived to have better cleaning ability . In conclusion . no clinical ly relevant differences in plaque reducing and gingivitis controlling ability were observed Three alternative toothbrushes were investigated in a double blind Latin Square repeated measures design study for their relative efficiency at removing plaque ' in vivo ' . A prototype filament suspension design toothbrush was tested , with the suspension mechanism both active and inactive , against a conventional toothbrush . Following an initial control plaque score , subjects were ordered by oral hygiene levels and r and omly allocated to each of the three test groups . The trial was made up of three periods of 14 days consisting of four days of no brushing followed by 10 days of brushing with each of the three toothbrushes . All plaque scores were recorded using the Greene and Vermillion Index of Oral Hygiene and plaque scores were recorded for each patient at the start , four days later and at the end of each 14-day period . There were no significant differences in the quantity of plaque remaining after brushing with any of the brushes tested in this study . Ignoring the toothbrush used , the end brushing average plaque scores for period 1 were found to be higher than the control plaque scores . It is suggested that this result ed from the patients finding new toothbrushes less comfortable to use initially but following a period of accommodation and adjustment , end brushing plaque levels in subsequent periods returned to near the same level as the control plaque score A thirty-day clinical trial was undertaken with second grade school children to assess the safety and efficacy of a new battery-powered toothbrush ( Rowenta Dentiphant ) compared to the manual Oral-B 20 toothbrush . The children from four class rooms were individually and r and omly assigned to use either product for the thirty days . The children reported to school having not brushed the morning of each assessment at baseline , 15 days and 30 days . Following the gingivitis assessment and given a pre-brushing plaque assessment , the children were instructed on the use of the toothbrush as they then brushed their teeth for a timed 1 minute out of sight of the examiners . The children were then reassessed for plaque removal . The results demonstrated that the children using the Rowenta powered toothbrush became used to the brush and improved their cleaning efficiency during the study . By week two , the buccal plaque scores for the Rowenta brush were significantly lower ( p < 0.05 ) compared to the Oral-B 20 group . By week four the Rowenta subjects had significantly lower buccal and lingual plaque scores after brushing , while the Oral-B 20 subjects had significantly lower buccal scores after toothbrushing , but no significant difference was found after brushing on lingual surfaces for plaque removal . On total plaque area scores , the Rowenta group was significantly lower ( p < 0.01 ) than the Oral-B 20 group at both two and four weeks . The Rowenta group had a 10 % reduction in plaque area after brushing comparing baseline to four weeks . The Oral-B group demonstrated no percentage difference in after brushing plaque scores from baseline to four weeks . On gingivitis , the Rowenta group had significantly lower buccal and lingual mean scores compared to the Oral-B 20 group at week two , and lingual mean scores compared to the Oral-B 20 group at week four . The Rowenta group demonstrated a 27 % decrease in lingual gingivitis scores compared to baseline , while the Oral-B group had an 11 % decrease in lingual gingivitis scores from baseline to four weeks . Total gingivitis scores for the Rowenta group were significantly lower ( p < 0.01 - 0.001 ) at both weeks two and four compared to the Oral-B 20 group , with percentage declines from baseline to four weeks being 22 % and 12 % , respectively . The Rowenta Dentiphant toothbrush was found to be safe to use . On total plaque and gingivitis reduction , the Rowenta Dentiphant toothbrush was found to be significantly superior to the Oral-B 20 manual toothbrush by two weeks of use and this continued to the conclusion of the study In the present crossover clinical trial , the plaque-removing efficacy of a counterrotational toothbrush was compared to that of a normal toothbrush in orthodontic patients . Twenty subjects , aged 11 to 26 years , who had orthodontic brackets on all fully erupted teeth of at least one arch were selected . At the first appointment , a prophylaxis was given to bring the plaque score to 0 . Ten subjects received counterrotational brushes , and 10 subjects received manual brushes according to a r and omized list . At 14 days , plaque scores were recorded and another prophylaxis was given . The subjects who were using the electric brush were assigned to the manual brush and vice versa . At 28 days , plaque scores were reassessed . Results showed that the counterrotational brush was significantly more effective in removing supragingival plaque from bracketed teeth than was the manual brush . The differences in plaque-removing effectiveness were particularly consistent on the proximal surfaces of the teeth PURPOSE Recently , a new power toothbrush has been marketed with a design that fundamentally differs from other marketed power toothbrushes , in that it incorporates a round oscillating head , in conjunction with fixed bristles . The objective of this study was to compare the plaque removal efficacy of a control manual toothbrush ( Colgate Navigator ) to this experimental power toothbrush ( Crest SpinBrush ) following a single use . MATERIAL S AND METHODS This study was a r and omized , controlled , examiner-blind , 4-period crossover design which examined plaque removal with the two toothbrushes following a single use in 40 completed subjects . Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index . RESULTS Baseline plaque scores were 1.77 for both the experimental toothbrush and control toothbrush treatment groups . With respect to all surfaces examined , the experimental toothbrush delivered an adjusted ( via analysis of covariance ) mean difference between baseline and post-brushing plaque scores of 0.48 while the control toothbrush delivered an adjusted mean difference of 0.35 . The experimental toothbrush removed , on average , 37.6 % more plaque than the control toothbrush . These results were statistically significant ( P < 0.001 ) . With respect to buccal surfaces , the experimental toothbrush delivered an adjusted mean difference between baseline and post-brushing plaque scores of 0.54 while the control toothbrush delivered an adjusted mean difference of 0.42 . This represents 27.8 % more plaque removal with the experimental toothbrush compared to the control toothbrush . These results were also statistically significant ( P= 0.001 ) . Results on lingual surfaces also demonstrated statistically significantly ( P < 0.001 ) greater plaque removal for the experimental toothbrush with an average of 53.4 % more plaque removal The purpose of this study was to evaluate the effectiveness of an ultrasonic toothbrush to reduce plaque and gingival inflammation when compared to a manual toothbrush . 62 healthy adult patients with a plaque index of at least 2.0 , a 50 % bleeding index and at least 16 natural teeth participated in this study . 31 patients were r and omly assigned to the manual toothbrush group ( group A ) and 31 were assigned to an ultrasonic toothbrush group ( group B ) . The Turesky et al. plaque index ( PI ) , Eastman bleeding index , and Loe & Silness gingival index ( GI ) were performed at baseline , 15 , and 30 days at the beginning of each appointment ( pre-brushing ) . Patients then brushed with their assigned toothbrush and a post-brushing plaque index was recorded . Kruskal-Wallis one-way analysis of variance ( ANOVA ) was performed to determine between group differences on the parameters of all clinical indices . Results of the pre-brushing plaque index in group B were significantly lower at 15 and 30 days compared to group A. The post-brushing plaque index demonstrated no statistically significant between or within group differences . Both groups demonstrated significant within group reductions in GI and BI from baseline to 15 days and from 15 to 30 days , however , no between group differences were noted . The results of this study support the ability of an ultrasonic toothbrush to significantly remove plaque and reduce inflammation as well as a manual toothbrush over a 30 day period PURPOSE To compare the safety and efficacy of a new power toothbrush ( Braun Oral-B D17 ) with an ADA reference manual toothbrush . MATERIAL S AND METHODS 110 healthy subjects , 18 - 65 yrs of age , with a mean plaque index of > or = 1.80 and a gingival index of > or = 1.00 , were enrolled in this 3-month , r and omized , parallel-group , examiner-blind study . Oral soft and hard tissues were examined for safety , and plaque , gingivitis and bleeding were measured to evaluate efficacy . Measurements were made at baseline and after 1 and 3 months of product use . Following the baseline visit and r and omization , subjects were instructed to brush twice daily for 2 mins with their assigned brush . RESULTS 101 subjects completed the study with evaluable data for all time periods , 52 in the D17 group and 49 in the manual group . None of the nine withdrawals from the study were related to product use and no product-related adverse effects were reported . There was no clinical ly significant soft or hard tissue abrasion observed at any time point in either group . After 1 and 3 months , significant reductions from baseline in whole mouth and interproximal plaque , gingivitis and bleeding were observed in both groups . A comparison of the two groups revealed that the whole mouth and approximal plaque indices were reduced to a significantly greater extent in the D17 group after both 1 and 3 months . The whole mouth gingival index was also reduced to a greater extent in the D17 group at 1 and 3 months , but a difference in the approximal gingival index was only apparent after 3 months . With respect to the bleeding index , there was a significant difference between the two groups for the whole mouth at both 1 and 3 months , but the differences in favor of the D17 for approximal values did not achieve statistical significance . In conclusion , the D17 was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis , compared with a manual toothbrush This study analyzed the difference in effectiveness of a well-known manual toothbrush and a counterrotational electric toothbrush over medium- and long-term periods . Six dental students and six patients with moderate periodontitis participated in a split-mouth , single-blind experiment with repeated recordings of pocket depths and plaque and gingivitis indices . During the experiment , the use of interdental aids or mouth rinses was forbidden . At all intervals up to week 34 , manual brushing result ed in significantly less plaque removal , especially at approximal sites . Use of the counterrotational electric toothbrush result ed in a significantly greater reduction in gingival inflammation and significantly increased pocket reduction , especially in the periodontitis group . A crossover experiment confirmed the inferiority of the manual cleaning . The long-term observations showed a slight decrease in efficiency of both brushes , thereby justifying the need for regular motivation reinforcement . The results of the current study demonstrate the long-term superiority of a counterrotational electric toothbrush over the manual toothbrush The purpose of this study was to compare the Rotadent rotary electric toothbrush with conventional toothbrushing for its effectiveness in controlling supragingival plaque and gingival inflammation in periodontal maintenance patients . Forty subjects who had received periodontal treatment , including periodontal surgery , for moderate to advanced periodontitis and were on a 3-month periodontal maintenance were divided into two equal groups matched for age and sex . One group used conventional toothbrushing , dental floss , and toothpicks and the other used only the rotary electric toothbrush for a 12-month study period . Single-blind clinical assessment s ( Plaque Index , Gingival Index , bleeding tendency , pocket depth , and loss of attachment ) were made at baseline and at 3 , 6 , 9 , and 12 months after baseline . Subgingival debridement was performed 1 week after the baseline assessment and the 6- and 12-month examinations . Plaque removal was reinforced at 3-month intervals . Both groups had significantly improved scores ( P less than 0.01 ) for Gingival Index and bleeding tendency during the 12-month period , but no differences were found between the groups at any examination . These results indicate that the rotary electric toothbrush is as effective for plaque removal and control of gingival inflammation as a combination of conventional toothbrushing , flossing , and toothpicks for patients in periodontal maintenance This was a 2-part study . The purpose of the 1st part was to examine the relationship between brushing force and plaque removal efficacy comparing a regular manual toothbrush ( M ) with an electric toothbrush the Braun/Oral-B Plak Control ( B ) . The study consisted of a single oral prophylaxis followed by 5 experiments which differed solely in respect to toothbrushing force . At baseline ( after 24-h plaque accumulation ) , the amount of dental plaque was evaluated and subsequently , the subject 's mouth was brushed by a dental hygienist . Brushing was carried out in a r and om split-mouth order . Either the 1st and 3rd quadrants or the 2nd and 4th quadrants were brushed with 1 toothbrush and the 2 remaining quadrants with the other . The available time for the brushing procedure was 2 min . After brushing , the amount of remaining dental plaque was assessed . The force used in experiment 1 through 5 was 100 , 150 , 200 , 250 , 300 g , respectively . The results show that when brushing force is increased , more plaque is removed with either of the two brushes . Except for the high brushing force ( 300 g ) , the electric toothbrush removed more plaque than the manual brush . The purpose of the 2nd part was to evaluate the habitual brushing force which individuals use with various toothbrushes . Besides a manual toothbrush ( M ) , 3 electric toothbrushes were examined , the Rotadent ( R ) , Interplak ( I ) and Braun ( B ) . 20 subjects were selected on the basis of being ' good brushers ' ( plaque score at screening < 25 % ) . At baseline , each subject r and omly received 1 of the 4 brushes . They were allowed a training period of 3 weeks at the end of which they were asked to abstain from brushing for at least 24 h. The plaque ( Turesky modification of the Quigley & Hein ) was scored , after which the subjects brushed their teeth ( 2 min ) with the assigned toothbrush equipped with a strain gauge . A computer set-up measured ( 100 Hz ) and calculated the mean brushing force . After brushing , the amount of remaining plaque was assessed . The design of the study was a 4-way cross-over . The results show that with a manual brush , considerably more force is used than with the electric brushes ( R = 96 , I = 119 , B = 146 , M = 273 ) . No significant relation between brushing force and plaque removal was demonstrated for any of the brushes Patients undergoing orthodontic treatment with fixed appliances are at risk of developing carious white spot lesions and gingival inflammation because of the challenge of oral hygiene . The purpose of this study was to evaluate under home conditions the effectiveness of three different types of electric toothbrushes during active appliance therapy : Interplak ( Bausch & Lomb , Berlin , Germany ) , Rota-dent ( Rota-dent , Kusnacht , Switzerl and ) , and Braun Oral-B Plaque Remover ( Braun/Oral-B , Kronberg , Germany ) . A manual technique , which included normal toothbrush , interdental brush , and dental floss , served as reference . The study was structured as a single-blind " Latin square design " study . Thirty-eight orthodontic patients were r and omly allocated to groups who , within the test period , alternately used the toothbrushes . Before getting a new toothbrush that was to be used for a period of 4 weeks , each patient received video and written instructions . For another 4 weeks , the patient returned to the usual oral hygiene procedures before receiving the next new toothbrush . Oral hygiene was evaluated at the start of a new test period and after 2 and 4 weeks . Clinical scores included a modified O'Leary Plaque Index and Ainamo Gingival Bleeding Index . Wilcoxon rank testing for aggregated surfaces revealed statistically significantly lower plaque scores for Rota-dent than for the manual technique ( p < 0.01 ) . For all other toothbrushes , no differences were found in comparison to the manual technique . For Plaque Indices of specific sites , statistical analysis revealed all electric toothbrushes to be equal to the manual technique . No differences in Gingival Bleeding Indices were found after 4 weeks with either toothbrush . Patients with poor oral hygiene who used Rota-dent and Braun Oral-B Plaque Remover OD5 had statistically significantly lower plaque scores compared with the manual technique ( p < 0.01 ; p < 0.05 ) ; for patients with good oral hygiene , these differences were neutralized . It may be concluded that electric toothbrushes of the new generation are a real alternative to the often laborious manual tooth cleaning procedures used during active appliance therapy . Patients with poor oral hygiene may benefit from them especially because plaque removal can be achieved easier and faster The purpose of the present study was to evaluate the effect of an electronic toothbrush on established plaque and gingivitis in a 5-month clinical trial . This electronic toothbrush sends approximately a 0.15 mA current through the brushhead which presumedly enhances the efficacy of the brush in plaque elimination . For this study , 80 volunteers ( non-dental University students ) were selected on the basis of having moderate gingival inflammation . At baseline , plaque and bleeding upon probing were assessed on the vestibular , mesio-vestibular , distovestibular and lingual surfaces using the ' half-mouth ' design . After 2-months and 5-months , these clinical indices were again recorded . At each assessment , the participants received a new brushhead . All baseline indices appeared to be well-balanced . A mean Silness and Löe plaque score of 1.70 and 1.64 were found in the control and test groups , respectively . Little change was observed from baseline to 5-months . The Quigley and Hein plaque index behaved comparably . The mean bleeding upon probing score at baseline was 1.43 and 1.39 for the control and test group , respectively . Little to no improvement was observed in the course of this study . No beneficial effect could be shown for this ' electronic ' design of manual toothbrush In the present clinical trial , the effect on existing plaque and gingivitis of a new electric toothbrush ( ET ) was compared to that of a manual toothbrush ( MT ) . 40 medical students , age 18 - 30 years , participated . Plaque index ( PlI ) and gingival index ( GI ) were recorded at 6 sites at all teeth . At baseline , a PlI and GI > 1 were required . The participants were at r and om allocated to a group using either ET or MT and were instructed only to use the assigned toothbrush , brushing each morning and evening for 2 min . No oral hygiene instruction was given . Re-examination was done after 1 , 2 and 6 weeks . In the MT group , a minor decrease in mean PlI was found after 6 weeks ( all sites : from 1.2 to 1.1 , approximal sites : from 1.4 to 1.2 ) . The corresponding figures in the ET group were : 1.2 to 0.6 and 1.4 to 0.8 . After 6 weeks , the % of sites with visible plaque with MT was : 24 % ( all sites ) and 30 % ( approximal sites ) and with ET 8 % and 9 % , respectively . With MT , mean GI was unchanged after 6 weeks compared to baseline , whereas with ET , the changes were from 1.1 to 0.9 ( all sites ) and from 1.1 to 1.0 ( approximal sites ) . The % of sites with GI score > or = 2 had not changed after 6 weeks with MT ( all sites : 11 % , approximal sites : 13 % ) . With ET , these results were 3 % and 4 % , respectively Recent studies have suggested that a sonic electric toothbrush is more effective than a manual brush at removing extrinsic dental stain . There have been few studies of the comparative stain removal properties of different electric brushes . The study reported here was conducted to compare the efficacy of the sonic toothbrush ( Sonicare ) with an oscillating/rotating brush ( Braun Oral-B Plaque Remover ) and a conventional manual brush ( Crest Complete ) . The study was a single-blind , r and omized , cross-over design , balanced for residual effects and employing 24 subjects . Stain was enhanced over a 21-day period by twice-daily rinses with chlorhexidine and frequent intakes of tea and /or coffee . At the end of each period , tooth stain intensity and area , tongue stain intensity and area , lower lingual calculus and subjective tooth sensitivity were recorded together with preference for the brushes determined at the study 's completion . Similar levels of tongue staining were recorded for the three periods , with no significant differences between the three groups . Tooth stain intensity , for most sites , was not significantly different between the three groups . For mean total stain area and for lingual and lingual interproximal sites , a significant reduction in stain was seen following use of the oscillating/rotating brush compared to the manual brush . The reductions in stain with the sonic brush were not significantly different from the manual brush . With the exception of maximum stain intensity , there were no significant differences between the oscillating/rotating and sonic brushes . Significantly less tooth sensitivity was found following use of the oscillating/rotating brush compared to both the manual and sonic brushes . All three brushes were found to be safe , but volunteer preference significantly and predominantly favored the oscillating/rotating brush . The results suggest that the oscillating/rotating brush is superior to a manual brush for stain removal The aim of the study was to evaluate the cleanliness achieved with and the number of gingival lesions caused by brushing with a manual , multitufted toothbrush and an electric toothbrush that oscillated horizontally and vertically . Fifteen female dental assistant students participated in the crossover clinical trial . Eight students brushed their teeth for the first 2 weeks with the multitufted manual brush and seven with the electric brush . For the next 2 weeks the brush assignment was reversed . After the two brushing periods the number of gingival lesions and the amount of stained plaque were recorded . The manual toothbrush caused more gingival lesions than the electric brush ( P less than 0.05 ) . With regard to plaque scores , no difference was found between manual and electric brushing OBJECTIVES The purpose of this clinical study was to evaluate the efficacy of the Ultra Sonex Ultima(R ) in comparison with a conventional manual toothbrush . MATERIAL AND METHODS In all , 64 healthy volunteers ( 32 females , 32 males ) took part in the parallel- design treatment-blind study . After a screening examination and stratification by age , sex and papillary bleeding index ( PBI ) , the participants were r and omly assigned to two groups with 32 subjects each . Four weeks later , the Turesky modification of the Quigley-Hein plaque index ( PI ) , the approximal plaque index ( API ) , and the PBI were recorded at baseline . Four and 8 weeks after baseline , the indices were recorded again . RESULTS During the study period of 8 weeks , the API showed no difference between the manual and the electric toothbrush . For the median PI , a statistically significant difference ( p < 0.001 ) was found after 4 ( manual : 2.16 vs. electric : 1.34 ) and 8 weeks ( 1.96 vs. 0.92 ) . After 4 weeks , the median PBI was 0.75 for the manual and 0.43 for the electric brush ( p < 0.01 ) . The values after 8 weeks were 0.63 ( manual ) and 0.29 ( electric , p < 0.001 ) . CONCLUSION The Ultra Sonex Ultima may be more efficacious than manual toothbrushes in removing plaque and preventing gingivitis in patients without severe periodontal disease This study evaluated the long-term effect of an ultrasonic toothbrush used as part of a daily oral hygiene regimen on supragingival plaque , gingivitis , and gingival bleeding . Compared with a conventional toothbrush , the ultrasonic toothbrush was significantly more effective in reducing plaque formation ( p < 0.05 ) , removing plaque ( p < 0.05 ) , and reducing gingivitis ( p < 0.05 ) during the 6-month study period STATEMENT OF PROBLEM Earlier studies on orthodontic brackets have shown a loss of bond strength after a sonic toothbrush was used . PURPOSE This in vitro study evaluated the difference in bond strength of single complete veneer crowns after being subjected to the equivalent of 2 years of brushing with sonic and counterrotational toothbrushes . MATERIAL AND METHODS Complete gold crowns were fabricated with a conventional indirect technique for 30 extracted , intact , prepared human premolar teeth . Castings were then luted to the teeth with glass ionomer cement . Teeth were r and omly divided into 3 groups of 10 teeth each , 1 group to be brushed with Sonicare sonic toothbrush , 1 group to be brushed with Interplak counterrotational mechanical toothbrush , and 1 group as the control . Groups 1 and 2 were then brushed for the equivalent of 2 years per tooth . A uniform force of 50 g for the sonic toothbrush and 120 g for the counterrotational toothbrush was used . Control specimens were not brushed . Brush heads and sample teeth in contact with the toothbrush were kept moist at all times . Tensile dislodgment force was determined with an Instron universal testing machine . RESULTS The castings brushed with a sonic toothbrush required a mean of 43.22 kg ( + /- 11.16 ) force to remove the crowns from the teeth , whereas the counterrotational group required a mean of 42.87 kg ( + /- 10.42 ) and the control group a mean of 42.12 kg ( + /- 6.61 ) . Analysis of variance on the force data indicated no differences among the 3 groups in the force needed to remove the castings ( F[2,24 ] = 0.031 , P = .97 ) . CONCLUSION This in vitro study demonstrated no significant differences between groups in the amount of tensile dislodgment force required to remove cemented full veneer crowns from prepared teeth after brushing for the equivalent of 2 years time with a sonic toothbrush or a counterrotational toothbrush |
11,131 | 29,190,038 | Given the limitations of all studies in terms of bias and the low quality of available evidence , a clear conclusion regarding superiority of any one particular type of mechanical device over another is not possible .
Evidence is insufficient at present to advocate omission of conventional ligature-based appendix stump closure in favour of any single type of mechanical device over another in uncomplicated appendicitis | BACKGROUND Laparoscopic appendectomy is amongst the most common general surgical procedures performed in the developed world .
Arguably , the most critical part of this procedure is effective closure of the appendix stump to prevent catastrophic intra-abdominal complications from a faecal leak into the abdominal cavity .
A variety of methods to close the appendix stump are used worldwide ; these can be broadly divided into traditional ligatures ( such as intracorporeal or extracorporeal ligatures or Roeder loops ) and mechanical devices ( such as stapling devices , clips , or electrothermal devices ) .
However , the optimal method remains unclear .
OBJECTIVES To compare all surgical techniques now used for appendix stump closure during laparoscopic appendectomy . | The aim of this prospect i ve r and omized trial was to evaluate the clinical outcomes of hem-o-lok ligation system in laparoscopic appendix stump closure by comparing the endoloop ligature . A total of 53 patients were evaluated in this study ( n=26 and 27 for hem-o-lok and endoloop groups , respectively ) . The mean operation time were shorter in hem-o-lok group than endoloop group ( 64.7±19.2 vs. 75.4±23 , respectively ) ; however , the difference was not significant . Other surgical findings were similar . There was no statistically significant difference in overall nonsurgically or surgically related complications . The mean postoperative hospitalization time was also similar in both groups . Although it is not possible to make general conclusions on basis of such a limited study , in our opinion , closure of the appendix stump with polymeric nonabsorbable clips in laparoscopic appendectomy may be a cheaper and simpler alternative to other widely used methods A very important step in laparoscopic appendectomy is dissection of the appendiceal mesenteric pedicle . The aim of this study was to investigate the effect of LigaSure in laparoscopic appendectomy . Between August 2007 and June 2008 , a total of 32 patients were included in the study . Patients were r and omized into 2 groups . The first group 's dissection of the mesoappendix was performed with LigaSure ( 5 to 10 mm ) , whereas the second group 's with endodissector and endoclip . The surgical time , postoperative complications , additional analgesics use and hospital stay were compared . There were no significant differences in complication rates , use of analgesics and hospital stay between the groups . The operation time ( 49.06±14.73 min vs. 59.69±12.54 min , P=0.036 ) was significantly lower in the LigaSure group . This study demonstrates that dissection of the mesoappendix with LigaSure reduces the operation time and could be used safely . However , more experiences are needed to attain reliable scientific results A r and omized control trial was performed to evaluate the effectiveness and safety of absorbable polymeric clips for appendicular stump closure in laparoscopic appendectomy ( LA ) . Patients were r and omly enrolled into an experimental group ( ligation of the appendicular base with Lapro-Clips , L-C group ) or control group ( ligation of the appendicular base with Hem-o-lok Clips , H-C group ) . We identified 1,100 patients who underwent LA between April 1 , 2012 and February 3 , 2015 . Overall , 99 patients ( 9.0 % , 99/1,100 ) developed a complication following LA ( 47 [ 8.5 % ] in the L-C group and 52 [ 9.5 % ] in the H-C group ( P = 0.598 ) . No statistically significant differences were observed in intra-abdominal abscesses , stump leakage , superficial wound infections , post-operative abdominal pain , overall adverse events , or the duration of the operations and hospital stays between the groups ( all p > 0.05 ) . Adverse risk factors associated with the use of absorbable clips in LA included body mass index ≥ 27.5 kg/m2 , diabetes , American Society of Anesthesiologists degree ≥ III , gangrenous appendicitis , severe inflammation of the appendix base , appendix perforation , and the absence of peritoneal drainage . The results indicate that the Lapro-Clip is a safe and effective device for closing the appendicular stump in LA in select patients with appendicitis Background The aim of this study was to evaluate the feasibility , morbidity , and cost-effectiveness of the closure of the appendicular stump with a single non-absorbable polymeric clip compared with the closure of the appendicular stump with a stapler . Methods From January 2009 to December 2009 , 82 patients , 31 males and 51 females ( mean age of 35.4 years ; range of 17 to 79 years ) , were included in this prospect i ve , non-r and omized trial . In 56 patients , the appendicular stump was closed by staplers , and in 26 patients , a single Hem-o-lok MLX polymeric clip was applied . The data collected included age , sex , time of surgery , costs , time of hospitalization , day-time of surgery , complications , and preoperative white blood count ( WBC ) and c-reactive protein ( CRP ) . Results There were no differences between the two groups regarding age , sex , WBC , CRP , and time of hospitalization . Time of surgery was longer in the clip group due to the introductory phase . Morbidity did not differ significantly and was highly acceptable in both groups . The costs of one set of Hem-o-lock clips were negligible compared to staplers ( 19.94 € versus 356.43 € ) . Conclusions The use of a single non-absorbable polymeric clip is easy to use even for surgical trainees ; it is safe and cost-effective . We suggest the use of a single clip for the closure of the appendicular stump as the st and ard procedure in laparoscopic appendectomy whenever possible We compared 140 appendectomies in a prospect i ve study with regard to length of operation , stay in hospital and intra- and postoperative complications . We operated by four methods and made up four groups , 35 patients in each : ( 1 ) application of RODER-loop and manual stump-sinking ; ( 2 ) application of RODER-loop without manual stump-sinking ; ( 3 ) application of Endo-GIA ; ( 4 ) conventional appendectomy according to McBurney . Intraoperative complications occurred mainly in laparoscopic appendectomy , while disturbances of wound-healing were observed mainly in conventional appendectomy . The analysis of postoperative complications in laparoscopic appendectomy showed the most complications in the second group ( RODER-loop without stump-sinking ) , while using the Endo-GIA involved only a little risk . In a clear situs the laparoscopic appendectomy with the RODER-loop with manual stump-sinking is recommended ; in cases with a difficult preparation or advanced appendicitis the application of the Endo-GIA is a safe technique with the best results Background : Laparoscopic appendectomy is a well-described surgical technique . However , concerns still exist regarding whether the closure of the appendiceal stump should be done with a clip , an endoloop , or other techniques . In this study , the effect of stump closure on duration of surgery and complications by endoclips was compared with endoloop in patients under laparoscopic appendectomy . The study was carried out as a prospect i ve r and omized clinical trial between 2013 and 2015 in Shariati Hospital of Tehran . Material s and Methods : Seventy-six patients under laparoscopic appendectomy were enrolled and r and omly assigned to receive either endoclips or endoloop for stump closure . The results in terms of the operating time , length of hospital stay , and the complications were compared and analyzed between two groups . After collecting the essential data by using a checklist and examination of patients , the data were analyzed with SPSS . Results : The mean age was 23.13 ± 5.07 years and 44.7 % of the patients were male . Moreover , in this study , it was seen that the mean duration of surgery was 23.2 min versus 21.5 min in endoloop and endoclips groups , respectively ( P = 0.021 ) . There was no difference between hospital stay among two groups ( P > 0.05 ) . Furthermore , the complications were same in two groups ( P > 0.05 ) . Conclusion : The effect of stump closure with endoloop versus endoclips is not different for complications , but the duration of surgery was shorter in endoclips method . Both methods could be used based on the opinion of the surgeon without expecting a statistically significant difference in the results Purpose The purpose of this study was to investigate the safety and usefulness of the Hem-o-lok clip for the closure of appendicular stumps and limitations of the Hem-o-lok clip . Methods From May 2010 to August 2011 , 105 consecutive patients underwent laparoscopic appendectomies by three surgeons . XL size Hem-o-lok clips were used for the closure of appendicular stumps by one surgeon . The remaining surgeons used double endoloop ligatures . Prospect ively collected data from patients who underwent laparoscopic appendectomy due to acute appendicitis were retrospectively review ed . Results A total of 105 laparoscopic appendectomies were performed . The endoloop group consisted of 66 patients ( mean age , 34.6 years ; range , 16 to 82 years ) , while the Hem-o-lok group consisted of 39 patients ( mean age , 43.5 years ; range , 11 to 88 years ) . In three cases , the Hem-o-lok clip was not used due to enlargement and severe inflammation of the appendix base . No specific intraoperative or postoperative complications were observed in either group . Conclusion The use of Hem-o-lok clips for the closure of appendicular stumps in laparoscopic appendectomy is a feasible , safe , fast and cost-effective procedure in patients with a mildly to moderately inflamed appendix base of less than 10 mm in diameter Background : The objectives of this study were to establish whether the occlusion of the appendicular stump by using nonabsorbable polymeric clips is technically feasible and whether differences exist in the postoperative course of patients to whom polymeric clips are applied compared with patients whose appendicular stump is closed with a surgical stapler . Methods : This was a prospect i ve study in 2 stages . In phase 1 , 28 patients operated on for resection of the appendix between March 2002 and September 2003 were assigned to 1 of 2 groups . In 14 patients , the appendicular base was occluded by using an endoscopic linear cutting stapler . In the remaining 14 , the appendicular base was ligated by using nonabsorbable polymeric clips ( Hem-o-lock ) . We compared the surgical time , hospital stay , hospital costs , and complications . In phase 2 , 250 patients were analyzed who underwent laparoscopic appendectomies performed between March 2002 and 2006 using a Harmonic scalpel for the section and hemostasis of the appendicular mesentery . Ligation of the appendicular stump was performed with Hem-o-lock clips . Results : We found a significant difference in procedure costs , with the endoscopic staplers being more expensive . Conclusion : The use of polymeric clips is feasible , safe , and an economic alternative for ligation of the appendicular stump during laparoscopic appendectomies The applicability and safety of a new operative technique for laparoscopic appendectomy using an automatic stapling device , the Multifire Endo-GIA 30 , was evaluated . This instrument , which can be passed through a 12-mm trocar sleeve , compresses the appendix as well as the resting stump , occluding its lumen with three lines of titanium staples and cutting between them . Data from 40 laparoscopic appendectomy patients collected between August 1991 and March 1992 were analyzed prospect ively . Using this stapler , the mean operation time was 58.33 min ( range , 35 - 95 min ) , with no complications or mortality . In 35 cases , an acute , and in one case , a chronic , appendicitis was histologically confirmed ; in four cases no inflammation was detected . Our preliminary results suggest that this new stapling device offers a simple and safe method for use in laparoscopic appendectomy Background During laparoscopic appendectomy ( LA ) , the st and ard technique in securing of the base of the appendix is by endoloop ligatures . However , application of the endoloop dem and s dexterity and a short training , while hem-o-lok clips may be more advantageous to use due to their simplicity of application and low cost . The objective of this study was to evaluate the technical feasibility and eventual advantages of this way of securing of the base of the appendix . Patients and methods Prospect i ve study was conducted in the period from August 2006 to August 2008 . The patients were divided into two groups ; in the first group the base of the appendix was secured by double endoloop ligatures , while in the second group it was done by double nonabsorbable hem-o-lok clips . The data collected included age , gender , operative time , hospital stay , costs , and intra- and postoperative complications . Results There was no difference in hospital stay between the two groups of patients ; mean operative time was 47.1 ± 6.7 min in the first group where the base was secured by endoloop ligatures , and was 38.7 ± 5.0 min in the group where the base was secured by hem-o-lok clips . The cost of the three hem-o-lok clips was € 76.9 , and that of the three endoloop ligatures was € 88.5 . In hem-o-lok group of patients , one intraoperative complication was observed , involving bleeding of mesoappendix . There were no postoperative complications in either group of patients . Conclusion The simplicity of application , shorter time of operation , and lower cost of hem-o-lok clips are advantages of this way of securing of the base of the appendix in relation to the st and ard endoloop procedure Patients and surgeons frequently opt for laparoscopic appendectomy for treatment of acute appendicitis . Clinical studies have shown this approach to be a reasonable alternative to open appendectomy . The objective of the current study was to assess the outcome of laparoscopic appendectomy using three different techniques . The study sample consisted of 150 children with acute appendicitis who underwent surgery at Al-Azhar University Hospitals , Cairo , Egypt , and at Al Mishary Hospital in Riyadh , Saudi Arabia , between October 1997 and October 1999 . The patients were allocated to undergo extracorporeal laparoscopic appendectomy , Endoloop laparoscopic appendectomy , or EndoGIA ( Ethicon Endo-surgery , Inc. , Cincinnati , OH , USA ) laparoscopic appendectomy . All patients were assessed for the severity of the disease at baseline using clinical and hematologic indicators . The ages of the children ranged from 7 to 14 years , with a mean of 10 years ( SD , 2.14 years ) . Of the children , 55.3 % were female . The results showed that children who underwent laparoscopic appendectomy using the EndoGIA had statistically significant shorter operating times , did not have complications , and had the shortest duration of hospital stay ( although duration of hospital stay did not reach the statistically significant level of P > 0.05 ) . Therefore , the study showed that laparoscopic appendectomy using the EndoGIA is the procedure that is most recommended , except for the relatively high cost of the disposable material s. Endoloop laparoscopic technique was the second most preferable procedure , and the least preferred procedure was extracorporeal laparoscopically assisted appendectomy . The major drawback of the last technique is the high frequency of complications . Endoloop laparoscopic appendectomy with a purse-string suture can be performed safely if the EndoGIA is not available Background : Laparoscopic appendectomy is a well-described surgical technique . However , concerns still exist regarding whether the closure of the appendiceal stump should be done with a clip , an endoloop , staples , or other techniques . Therefore , several modifications to the original technique with new material s have been introduced for appendiceal stump closure . The aim of this study was to compare intracorporeal ( polyglactin ) knot-tying suture with titanium endoclips in appendiceal stump closure during laparoscopic appendectomy . Methods : The study was carried out as a prospect i ve r and omized clinical trial between April 2010 and February 2011 . Patients with a presentation of appendicitis were included into the study . Two groups were defined— patients with the titanium endoclip and patients with the knot-tying ( polyglactin ) suture . The results in terms of operating time , complication rates , and hospital stay were analyzed . Results : Sixty-one patients who underwent laparoscopic appendectomy were enrolled in the titanium endoclip group ( n=30 ) or the knot-tying ( polyglactin ) suture group ( n=31 ) . No statistically significant differences were detected between the groups in terms of the distribution of age , sex percentage , appendix localization , and histopathologic diagnosis ( P>0.05 ) . One patient required a second operation on postoperative day 10 because of intraperitoneal abscess . The mean operative time for the endoclip group ( 41.27±12.2 min ) was shorter than that for the knot-tying group ( 62.81±15.4 min ) ( P=0.001 ) . No statistically significant differences were detected between the groups in terms of hospital stay , follow-up time , and preoperative and postoperative complications ( P>0.05 ) . Conclusions : In laparoscopic appendectomy , using a titanium endoclip for optimizing and controlling the appendiceal stump closure is safe and is associated with shorter operation time . This also simplifies the procedure , so it can be a useful alternative to intracorporeal knot-tying for appendiceal stump closure BACKGROUND During laparoscopic appendectomy , the st and ard technique in securing the base of the appendix is by endoloop ligatures or a stapler . We earlier demonstrated the possibility of the application of a double Hem-o-lok ( ® ) clip in securing of the base of the appendix . The application of only one plastic clip would , however , lower the cost of the laparoscopic procedure even further and shorten the surgery time . The objective of this prospect i ve study was to evaluate the possible advantages of securing of the base of the appendix using only one Hem-o-lok clip . PATIENTS AND METHODS The 90 patients with acute appendicitis were r and omly divided into three groups : In the first group , the base of the appendix was secured using one endoloop ligature , in the second group using a 45-mm stapler , and in the third group using only one nonabsorbable Hem-o-lok clip . The data collected included age , gender , surgery time , time of endoloop/stapler/clip application , hospital stay , costs associated with these , and intra- and postoperative complications . RESULTS There were no significant differences in hospital stay among the three groups of patients ; but the average time of the operation was significantly longer in the endoloop group than in the stapler group ( P=.002 ) , whereas the endoloop and Hem-o-lok groups were not statistically different ( P=.22 ) . The time of application of the endoloop was significantly longer than for the stapler ( P<.0001 ) and Hem-o-lok ( P<.0001 ) groups . The time of application of the stapler was significantly shorter than that of the Hem-o-lok ( P<.0001 ) . However , the price of one endoloop is € 28.85 , for the stapler is € 230.7 , and for one Hem-o-lok clip is € 2.35 . CONCLUSION The use of one Hem-o-lok clip is as safe as an endoloop and /or stapler ; however , the time of the laparoscopic procedure using the Hem-o-lok was shorter in comparison with the use of an endoloop , with the cost of the procedure being the lowest Background Inadequate closure of the appendix stump can lead to abscess formation or peritonitis . This prospect i ve r and omized clinical trial was performed to evaluate the number of endoloops needed in laparoscopic appendectomy . Methods A total of 208 patients were r and omized in two groups : 109 in group 1 using one and 99 in group 2 using two proximal endoloops . The groups were compared in terms of intra- and postoperative complications . Results Postoperative complications were found in five patients ( 4.6 % ) in group 1 , consisting of intraabdominal abscesses ( three patients ) , pulmonary embolism ( one patient ) , and persisting port-site pain ( one patient ) . In group 2 , postoperative complications were found in five patients ( 5.1 % ) , consisting of intraabdominal abscesses ( four patients ) and prolonged percutaneous drainage ( one patient ) . There was no significant difference between the two groups . Discussion In acute appendicitis , a minimal inflamed appendix base can be safely divided using one endoloop Introduction : In this study , for the first time in children a polymer clip and endoloop ( EL ) for securing an appendiceal stump have been prospect ively correlated and evaluated radiologically . Methods : Forty-nine patients aged 1 to 15 years were operated upon by the same surgeon for acute or perforated appendicitis between May 2008 and May 2009 . The appendiceal stump was ligated by an EL or polymer clip . Patients were radiologically evaluated during the postoperative period . Results : In the EL group , the mean operating time for perforated appendicitis was recorded as 57.40 minutes and in nonperforated appendicitis as 39.37 minutes , respectively . In the clips-applied group , these periods were 48.23 and 34.72 minutes , respectively . Clip application is 3 times cheaper than EL . Conclusions : Polymer clip is an instrument that is cheaper , safe , easily applicable , and takes less time for securing appendiceal stumps compared with EL |
11,132 | 27,486,836 | Telemonitoring interventions may provide additional benefit for two measures of lung function .
AUTHORS ' CONCLUSIONS Current evidence does not support the widespread implementation of telemonitoring with healthcare provider feedback between asthma clinic visits .
Studies have not yet proven that additional telemonitoring strategies lead to better symptom control or reduced need for oral steroids over usual asthma care , nor have they ruled out unintended harms . | BACKGROUND Asthma is a chronic disease that causes reversible narrowing of the airways due to bronchoconstriction , inflammation and mucus production .
Asthma continues to be associated with significant avoidable morbidity and mortality .
Self management facilitated by a healthcare professional is important to keep symptoms controlled and to prevent exacerbations .
Telephone and Internet technologies can now be used by patients to measure lung function and asthma symptoms at home .
Patients can then share this information electronically with their healthcare provider , who can provide feedback between clinic visits .
Technology can be used in this manner to improve health outcomes and prevent the need for emergency treatment for people with asthma and other long-term health conditions .
OBJECTIVES To assess the efficacy and safety of home telemonitoring with healthcare professional feedback between clinic visits , compared with usual care . | OBJECTIVE To determine whether an asthma coaching program can improve parent and child asthma-related quality of life ( QOL ) and reduce urgent care events . DESIGN R and omized controlled trial of usual care vs usual care with coaching . Comparisons were made between groups using mixed models . SETTING A Midwest city . PARTICIPANTS A community-based sample of 362 families with a child aged 5 to 12 years with persistent asthma . INTERVENTION A 12-month structured telephone coaching program in which trained coaches provided education and support to parents for 4 key asthma management behaviors . MAIN OUTCOME MEASURES Parental and child QOL measured with a vali date d , interview-administered , 7-point instrument and urgent care events in a year ( unscheduled office visits , after-hours calls , emergency department visits , or hospitalizations ) determined by record audit . RESULTS Parental asthma-related QOL scores improved by an average of 0.67 units ( 95 % confidence interval [ CI ] , 0.49 to 0.84 ) in the intervention group and 0.28 units ( 95 % CI , 0.10 to 0.46 ) in the control group . The difference between study groups was statistically significant ( difference , 0.38 ; 95 % CI , 0.14 to 0.63 ) . No between-group difference was found in the change in the child 's QOL ( difference , -0.17 ; 95 % CI , -0.47 to 0.12 ) or in the mean number of urgent care events per year ( difference , 1.15 ; 95 % CI , 0.82 to 1.61 ) . The proportion of children with very poorly controlled asthma in the intervention group decreased compared with the control group ( difference , 0.34 ; 95 % CI , 0.21 to 0.48 ) . CONCLUSIONS A telephone coaching program can improve parental QOL and can be implemented without additional physician training or practice re design 263 participants completing a r and omised controlled trial comparing telephone vs. face-to-face asthma consultations were asked about preferences for future review s. Qualitative analysis of data from 209 respondents identified divergent views . Clear opinions were expressed about the respective roles of the two modes of consulting ; telephone consultations were considered convenient for review ing ' well controlled ' asthma , whereas face-to-face consultations were perceived as allowing in-depth assessment of problems in those with more symptomatic asthma . Practice s may consider offering patients the choice of a telephone or face-to-face review Background In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects . However , the optimal strategy for tapering oral corticosteroids is unknown . Objective To investigate whether an internet-based management tool including home monitoring of symptoms , lung function and fraction of exhaled nitric oxide ( FENO ) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life . Methods In a 6-month pragmatic r and omised prospect i ve multicentre study , 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies : according to conventional treatment ( n=43 ) or guided by a novel internet-based monitoring system ( internet strategy ) ( n=52 ) . Primary outcomes were cumulative sparing of prednisone , asthma control and asthma-related quality of life . Secondary outcomes were forced expiratory volume in 1 s ( FEV1 ) , exacerbations , hospitalisations and patient 's satisfaction with the tapering strategy . Results Median cumulative sparing of prednisone was 205 ( 25–75th percentile −221 to 777 ) mg in the internet strategy group compared with 0 ( −497 to 282 ) mg in the conventional treatment group ( p=0.02 ) . Changes in prednisone dose ( mixed effect regression model ) from baseline were −4.79 mg/day and + 1.59 mg/day , respectively ( p<0.001 ) . Asthma control , asthma-related quality of life , FEV1 , exacerbations , hospitalisations and satisfaction with the strategy were not different between groups . Conclusions An internet-based management tool including home monitoring of symptoms , lung function and FENO in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life . Clinical trial registration number Clinical trial registered with http://www.trialregister.nl ( Netherl and s Trial Register number 1146 ) Background : No r and omised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists . Most r and omised trials of asthma self-management have recruited participants from secondary care ; there is uncertainty regarding its effectiveness in primary care . A r and omised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy . Methods : Twenty four adults attending a community pharmacy in Tower Hamlets , east London for routine asthma medication were r and omised into two groups : the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist . Participants self-completed the North of Engl and asthma symptom scale at baseline and 3 months later . Results : The groups were well matched at baseline for demographic characteristics and mean ( SD ) symptom scores ( 26.3 ( 4.8 ) and 27.8 ( 3.7 ) in the intervention and control groups , respectively ) . Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 ( 4.2 ) and 28.1 ( 3.5 ) , respectively ( p<0.001 ; difference adjusted for baseline scores = 7.0 ( 95 % CI 4.4 to 9.5 ) . Conclusions : A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy . Further studies should attempt to confirm these findings using larger sample s and a wider range of outcome measures Background Many children with asthma do not have sufficient asthma control , which leads to increased healthcare costs and productivity loss of parents . One of the causative factors are adherence problems . Effective interventions improving medication adherence may therefore improve asthma control and reduce costs . A promising solution is sending real time text-messages via the mobile phone network , when a medicine is about to be forgotten . As the effect of real time text-messages in children with asthma is unknown , the primary aim of this study is to determine the effect of a Real Time Medication Monitoring system ( RTMM ) with text-messages on adherence to inhaled corticosteroids ( ICS ) . The secondary objective is to study the effects of RTMM on asthma control , quality of life and cost-effectiveness of treatment . Methods A multicenter , r and omized controlled trial involving 220 children ( 4–11 years ) using ICS for asthma . All children receive an RTMM-device for one year , which registers time and date of ICS doses . Children in the intervention group also receive tailored text-messages , sent only when a dose is at risk of omission . Primary outcome measure is the proportion of ICS dosages taken within the individually predefined time-interval . Secondary outcome measures include asthma control ( monthly Asthma Control Tests ) , asthma exacerbations , healthcare use ( collected from hospital records , patient reports and pharmacy record data ) , and disease-specific quality of life ( PAQLQ question naire ) . Parental and children ’s acceptance of RTMM is evaluated with online focus groups and patient question naires . An economic evaluation is performed adopting a societal perspective , including relevant healthcare costs and parental productivity loss . Furthermore , a decision-analytic model is developed in which different levels of adherence are associated with clinical and financial outcomes . Also , sensitivity analyses are carried out on different price levels for RTMM . Discussion If RTMM with tailored text-message reminders proves to be effective , this technique can be used in daily practice , which would support children with suboptimal adherence in their asthma (self)management and in achieving better asthma control and better quality of life . Trial registration Netherl and s Trial Register NTR2583 Background Asthma is a chronic lung disease in which recurrent asthma symptoms create a substantial burden to individuals and their families . At the same time the economic burden associated with asthma is considerable . Methods The cost-effectiveness study was part of a single centre prospect i ve r and omised controlled trial comparing a nurse-led telemonitoring programme to usual care in a population of asthmatic out patients . The study included 109 asthmatic out patients ( 56 children ; 53 adults ) . The duration of follow-up was 12 months , and measurements were performed at baseline , 4 , 8 , and 12 months . Patients were asked to transfer their monitor data at least twice daily and by judging the received data and following a stepwise intervention protocol a nurse was able to act as the main caregiver in the intervention group . In both groups the EQ-5D and the SF-6D were used to obtain estimates of health state utilities . One year health care costs , patient and family costs , and productivity losses were calculated . The mean incremental costs were weighted against the mean incremental effect in terms of QALY . Results The study population generally represented mild to moderate asthmatics . No significant differences were found between the groups with regard to the generic quality of life . Overall , the mean health care costs per patient were higher in the intervention group than in the control group . The intervention costs mainly caused the cost difference between the groups . The intervention costs the society € 31,035/QALY gained with regard to adults and with regard to children € 59,071/QALY gained . Conclusion If the outcome is measured by generic quality of life the nurse-led telemonitoring programme is of limited cost-effectiveness in the study population . From the societal perspective the probability of the programme being cost-effective compared to regular care was 85 % at a ceiling ratio of € 80,000/QALY gained among the adults and 68 % among the children . A decrease in the price of the asthma monitor will substantial increase the probability of the programme to be cost-effective . Trial registration Number : Background Asthma is a prevalent and costly disease result ing in reduced quality of life for a large proportion of individuals . Effective patient self-management is critical for improving health outcomes . However , key aspects of self-management such as self-monitoring of behaviours and symptoms , coupled with regular feedback from the health care team , are rarely addressed or integrated into ongoing care . Health information technology ( HIT ) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team , and access to their health information , presented in personalized ways that can alert them when there is a need for action . The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system , My Asthma Portal ( MAP ) , linked to a case-management system on asthma control , and asthma health-related quality of life . Methods The trial is a parallel multi-centered 2-arm pilot r and omized controlled trial . Participants are r and omly assigned to one of two conditions : a ) MAP and usual care ; or b ) usual care alone . Individuals will be included if they are between 18 and 70 , have a confirmed asthma diagnosis , and their asthma is classified as not well controlled by their physician . Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug data base , and asthma quality of life using the Mini Asthma Related Quality of Life Question naire . Power calculations indicated a needed total sample size of 80 subjects . Data are collected at baseline , 3 , 6 , and 9 months post r and omization . Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010 . Discussion Self-management support from the care team is critical for improving chronic disease outcomes . Given the high volume of patients and time constraints during clinical visits , primary care physicians have limited time to teach and reinforce use of proven self-management strategies . HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change . Trial Registration Current Controlled Trials IS RCT N34326236 Background Internet-based self-management has shown to improve asthma control and asthma related quality of life , but the improvements were only marginally clinical ly relevant for the group as a whole . We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma . Methods In a 1-year r and omised controlled trial involving 200 adults ( 18 - 50 years ) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Question naire ( ACQ ) . Participants were assigned either to the Internet group ( n = 101 ) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group ( UC ) ( n = 99 ) . We analysed 3 subgroups : patients with well controlled ( ACQ ≤ 0.75 ) , partly controlled ( 0.75>ACQ ≤ 1.5 ) or uncontrolled ( ACQ>1.5 ) asthma at baseline . Results Overall monitoring adherence was 67 % ( 95 % CI , 60 % to 74 % ) . Improvements in ACQ score after 12 months were -0.14 ( p = 0.23 ) , -0.52 ( p < 0.001 ) and -0.82 ( p < 0.001 ) in the Internet group compared to usual care for patients with well , partly and uncontrolled asthma at baseline , respectively . Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma ( + 278 μg , p = 0.001 ) , but not in patients with well or partly controlled asthma . After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care . Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients ' needs . Trial registration Current Controlled Trials IS RCT BACKGROUND Attendance for routine asthma review s is poor . A recent r and omised controlled trial found that telephone consultations can cost-effectively and safely enhance asthma review rates ; however , concerns have been expressed about the generalisability and implementation of the trial 's findings . AIM To evaluate the effectiveness of a telephone option as part of a routine structured asthma review service . DESIGN OF STUDY Phase IV controlled before- and -after implementation study . SETTING A large UK general practice . METHOD Using existing administrative groups , all patients with active asthma ( n = 1809 ) received one of three asthma review services : structured recall with a telephone-option for review s versus structured recall with face-to-face-only review s , or usual-care ( to assess secular trends ) . Main outcome measures were : proportion of patients with active asthma review ed within the previous 15 months ( Quality and Outcomes Framework target ) , mode of review , enablement , morbidity , and costs to the practice . RESULTS A routine asthma review was provided for 397/598 ( 66.4 % ) patients in the telephone-option group compared with 352/654 ( 53.8 % ) in the face-to-face-only review group : risk difference 12.6 % ( 95 % confidence interval [ CI ] = 7.2 to 17.9 , P<0.001 ) . The usual-care group achieved a review rate of 282/557 ( 50.6 % ) . Morbidity was equivalent in the three groups ; however , enablement ( P = 0.03 ) and confidence ( P = 0.007 ) in asthma management were greater in the telephone-option versus face-to-face-only group . The cost per review achieved by providing the telephone-option service was lower than the face-to-face-only service ( 10.03 pounds versus 12.74 pounds , mean difference 2.71 pounds ; 95 % CI = 1.92 to 3.50 , P<0.001 ) ; usual-care costs were 11.85 pounds per review achieved . CONCLUSION Routinely offering telephone review s cost-effectively increased asthma review rates , enhancing patient enablement and confidence with management , with no detriment to asthma morbidity . Practice s should consider a telephone option for their asthma review service Background Asthma is the most common chronic condition of childhood and disproportionately affects inner-city minority children . Low rates of asthma preventer medication adherence is a major contributor to poor asthma control in these patients . Web-based methods have potential to improve patient knowledge and medication adherence by providing interactive patient education , monitoring of symptoms and medication use , and by facilitation of communication and teamwork among patients and health care providers . Few studies have evaluated web-based asthma support environments using all of these potentially beneficial interventions . The multidimensional website created for this study , BostonBreathes , was design ed to intervene on multiple levels , and was evaluated in a pilot trial . Methods An interactive , engaging website for children with asthma was developed to promote adherence to asthma medications , provide a platform for teamwork between caregivers and patients , and to provide primary care providers with up-to- date symptom information and data on medication use . Fifty-eight ( 58 ) children primarily from inner city Boston with persistent-level asthma were r and omised to either usual care or use of BostonBreathes . Subjects completed asthma education activities , and reported their symptoms and medication use . Primary care providers used a separate interface to monitor their patients ’ website use , their reported symptoms and medication use , and were able to communicate online via a discussion board with their patients and with an asthma specialist . Results After 6-months , reported wheezing improved significantly in both intervention and control groups , and there were significant improvements in the intervention group only in night-time awakening and parental loss of sleep , but there were no significant differences between intervention and control groups in these measures . Emergency room or acute visits to a physician for asthma did not significantly change in either group . Among the subgroup of subjects with low controller medication adherence at baseline , adherence improved significantly only in the intervention group . Knowledge of the purpose of controller medicine increased significantly in the intervention group , a statistically significant improvement over the control group . Conclusions This pilot study suggests that a multidimensional web-based educational , monitoring , and communication platform may have positive influences on pediatric patients ’ asthma-related knowledge and use of asthma preventer medications A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88 participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers Background Asthma is a common medical condition caused by chronic inflammation of the airways . Characteristic symptoms of the illness include attacks of shortness of breath , wheezing , tightness in the chest , and cough . Asthma is commonly treated by inhaled corticosteroids , which help to suppress inflammation of the airways and reduce the frequency of severe symptoms and attacks . This medication in the form of inhalers is known as preventer or controller medication and many patients also take short-acting bronchodilators to control acute symptoms ( reliever medication ) . In order to provide therapeutic benefit , preventer medication needs to be taken regularly on a daily basis . However , non-adherence to preventer medication is a common problem in patients diagnosed with asthma and these results in the overuse of reliever medication , increased asthma symptoms , more frequent asthma attacks , and hospital admissions ( Stern et al. , 2006 ) . Optimal adherence to inhaled corticosteroids requires patients to take their preventer medication on 80 % or more occasions , as this is associated with greatest asthma control ( Lasmar et al. , 2009 ) . Objective While effective preventative medication is readily available for asthma , adherence is a major problem due to patients ’ beliefs about their illness and medication . We investigated whether a text message programme targeted at changing patients ’ illness and medication beliefs would improve adherence in young adult asthma patients . Methods Two hundred and sixteen patients aged between 16 and 45 on asthma preventer medication were recruited from pamphlets dispensed with medication and e-mails sent to members of a targeted marketing website . Participants were r and omized to receive individually tailored text messages based on their illness and medication beliefs over 18 weeks or no text messages . Illness and medication beliefs were assessed at baseline and at 18 weeks . Adherence rates were assessed by phone calls to participants at 6 , 12 , and 18 weeks and at 6 and 9 months . Results At 18 weeks , the intervention group had increased their perceived necessity of preventer medication , increased their belief in the long-term nature of their asthma , and their perceived control over their asthma relative to control group ( all p<0.05 ) . The intervention group also significantly improved adherence over the follow-up period compared to the control group with a relative average increase in adherence over the follow-up period of 10 % ( p<0.001 ) . The percentage taking over 80 % of prescribed inhaler doses was 23.9 % in the control group compared to 37.7 % in the intervention group ( p<0.05 ) . Conclusion A targeted text message programme increases adherence to asthma preventer inhaler and may be useful for other illnesses where adherence is a major issue Abstract Introduction : Originally , the Asthma Control Test ( ACT ) was design ed for English-speaking patients using a paper- and -pencil format . The Turkish version of the ACT was recently vali date d. This article compares the paper- and -pencil and web-based texting formats of the Turkish version of the ACT and evaluates the compatibility of these ACT scores with GINA-based physician assessment s of asthma control . Methods : This multicentre prospect i ve study included 431 asthma patients from outpatient clinics in Turkey . The patients were r and omized into a paper- and -pencil group ( n = 220 ) and a text messaging group ( n = 211 ) . Patients completed the ACT at Visit 1 , after 10 ± 2 days , and at 5 ± 1 week to demonstrate the reliability and responsiveness of the test . At each visit , physicians assessed patients ’ asthma control levels . Results : The ACT administered via texting showed an internal consistency of 0.82 . For the texting group , we found a significant correlation between the ACT and physician assessment s at Visit 1 ( r = 0.60 , p < 0.001 ) . The AUC was 0.87 , with a sensitivity of 78.0 % and a specificity of 77.5 % for a score of ≤19 for screening “ uncontrolled ” asthma in the texting group . Conclusion : When the Turkish version of the ACT was administered via either the paper- and -pencil or text messaging test , scores were closely associated with physician assessment s of asthma control Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 OBJECTIVES To test the hypothesis that reinforcement of the advice given at the time of discharge from the emergency department by telephone consultation would improve asthma outcomes . METHODS A r and omized controlled trial of the parents of 310 children who had been discharged from the emergency department with asthma was undertaken . The parents were r and omized to receive either st and ard care ( 155 children ) or st and ard care plus education by telephone ( 155 children ) from a trained asthma educator . Symptoms , parental asthma knowledge , parental quality of life and use of asthma action plans and preventer therapy were collected at baseline and 6 months later . The primary measure was days of wheeze in last 3 months ; intermediate measures were regular use of preventer medications , possession and use of written asthma action plan , parental asthma knowledge scores and parental quality of life scores . RESULTS A total of 266 parents ( 136 intervention ) completed the follow-up question naires after 6 months . Both groups showed similar symptoms and process measures at baseline , apart from more regular use of preventer medication in the control children . At follow up , the intervention group children were significantly more likely than controls to possess ( 87.5 % vs 72.3 % ; P = 0.002 ) a written asthma action plan . Possession of action plans increased from baseline in the intervention group but tended to decrease in the control group . Use of action plans was greater in the intervention group but decreased from baseline in both groups . Both intervention and control groups showed significant decreases in asthma symptoms . CONCLUSIONS Reinforcement by telephone consultation did not improve the primary outcome of wheeze in the last 3 months . However , it increased the possession and regular use of written asthma action plans in the intervention group Objective To assess the effect of home based telehealth interventions on the use of secondary healthcare and mortality . Design Pragmatic , multisite , cluster r and omised trial comparing telehealth with usual care , using data from routine administrative data sets . General practice was the unit of r and omisation . We allocated practice s using a minimisation algorithm , and did analyses by intention to treat . Setting 179 general practice s in three areas in Engl and . Participants 3230 people with diabetes , chronic obstructive pulmonary disease , or heart failure recruited from practice s between May 2008 and November 2009 . Interventions Telehealth involved remote exchange of data between patients and healthcare professionals as part of patients ’ diagnosis and management . Usual care reflected the range of services available in the trial sites , excluding telehealth . Main outcome measure Proportion of patients admitted to hospital during 12 month trial period . Results Patient characteristics were similar at baseline . Compared with controls , the intervention group had a lower admission proportion within 12 month follow-up ( odds ratio 0.82 , 95 % confidence interval 0.70 to 0.97 , P=0.017 ) . Mortality at 12 months was also lower for intervention patients than for controls ( 4.6 % v 8.3 % ; odds ratio 0.54 , 0.39 to 0.75 , P<0.001 ) . These differences in admissions and mortality remained significant after adjustment . The mean number of emergency admissions per head also differed between groups ( crude rates , intervention 0.54 v control 0.68 ) ; these changes were significant in unadjusted comparisons ( incidence rate ratio 0.81 , 0.65 to 1.00 , P=0.046 ) and after adjusting for a predictive risk score , but not after adjusting for baseline characteristics . Length of hospital stay was shorter for intervention patients than for controls ( mean bed days per head 4.87 v 5.68 ; geometric mean difference −0.64 days , −1.14 to −0.10 , P=0.023 , which remained significant after adjustment ) . Observed differences in other forms of hospital use , including notional costs , were not significant in general . Differences in emergency admissions were greatest at the beginning of the trial , during which we observed a particularly large increase for the control group . Conclusions Telehealth is associated with lower mortality and emergency admission rates . The reasons for the short term increases in admissions for the control group are not clear , but the trial recruitment processes could have had an effect . Trial registration number International St and ard R and omised Controlled Trial Number Register IS RCT N43002091 OBJECTIVE Low-income and minority adolescents are at high risk for poor asthma outcomes , due in part to adherence . We tested acceptability , feasibility , and effect sizes of an adherence intervention for low socioeconomic status ( SES ) minority youth with moderate- and severe-persistent asthma . Design and Methods Single-site r and omized pilot trial : intervention ( n = 12 ; asthma education , motivational interviewing , problem-solving skills training , 1 month cell-phone with tailored text messaging ) versus control ( n = 14 ; asthma education ; cell-phone without tailored messaging ) . Calculated effect-sizes of relative change from baseline ( 1 and 3 months ) . RESULTS Intervention was judged acceptable and feasible by participants . Participants ( 12 - 18 years , mean = 15.1 , SD = 1.67 ) were 76.9 % African-American , 80.7 % public/no insurance . At 1 and 3 months , asthma symptoms ( Cohen 's d 's = 0.40 , 0.96 ) and HRQOL ( PedsQL ™ ; Cohen 's d 's = 0.23 , 1.25 ) had clinical ly meaningful medium to large effect sizes . CONCLUSIONS This intervention appears promising for at-risk youth with moderate- and severe-persistent asthma Background Internet-based self-management ( IBSM ) support cost-effectively improves asthma control , asthma related quality of life , number of symptom-free days , and lung function in patients with mild to moderate persistent asthma . The current challenge is to implement IBSM in clinical practice . Methods / design This study is a three-arm cluster r and omized trial with a cluster pre-r and omisation design and 12 months follow-up per practice comparing the following three IBSM implementation strategies : minimum strategy ( MS ) : dissemination of the IBSM program ; intermediate strategy ( IS ) : MS + start-up support for professionals ( i.e. , support in selection of the appropriate population and training of professionals ) ; and extended strategy ( ES ) : IS + additional training and ongoing support for professionals . Because the implementation strategies ( interventions ) are primarily targeted at general practice s , r and omisation will occur at practice level . In this study , we aim to evaluate 14 primary care practice s per strategy in the Leiden-The Hague region , involving 140 patients per arm . Patients aged 18 to 50 years , with a physician diagnosis of asthma , prescription of inhaled corticosteroids , and /or montelukast for ≥3 months in the previous year are eligible to participate . Primary outcome measures are the proportion of referred patients that participate in IBSM , and the proportion of patients that have clinical ly relevant improvement in the asthma-related quality of life . The secondary effect measures are clinical outcomes ( asthma control , lung function , usage of airway treatment , and presence of exacerbations ) ; self-management related outcomes ( health education impact , medication adherence , and illness perceptions ) ; and patient utilities . Process measures are the proportion of practice s that participate in IBSM and adherence of professionals to implementation strategies . Cost-effective measurements are medical costs and healthcare consumption . Follow-up is six months per patient . Discussion This study provides insight in the amount of support that is required by general practice s for cost-effective implementation of IBSM . Additionally , design and results can be beneficial for implementation of other self-management initiatives in clinical practice .Trial registration the Netherl and s National Trial Register Background Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients . Pharmacists are suited to impact medication adherence given their training , skills , and frequent contact with patients . The Empowering pharmacists in asthma management through interactive SMS ( EmPhAsIS ) trial involves an intervention leveraging mobile health ( mHealth ) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma . Methods / Design This study is a pragmatic pharmacy-based , cluster , r and omized controlled trial with 12 months of intervention delivery and follow-up . Pharmacies ( the clusters ) will be r and omized at a 1:1 ratio to provide intervention or usual care . The EmPhAsIS intervention consists of patient asthma education , short message service (SMS)-based monthly assessment of adherence , and follow-up of non-adherent individuals by community pharmacists . There are no inclusion or exclusion criteria for pharmacies . Patients are eligible if they : are 14 years of age or older , fill a prescription for inhaled corticosteroid ( either monotherapy or in a combination inhaler with long-acting beta-agonists ) , have been diagnosed with asthma , possess a mobile phone with SMS capabilities , and have no communication difficulties such as inability to communicate in English , or significant impairment in vision , hearing , or speech . The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio , the ratio of the days of medication supplied to days in a given time interval . This study will also evaluate secondary outcomes including : asthma control , asthma-related quality of life , asthma-related hospital admissions , and use of reliever medications during the follow-up period . A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon . Discussion Considering the prevalence of asthma , the extent of the non-adherence problem in this disease , and the availability of effective treatments , there is a tremendous potential to reduce the burden of asthma through improving adherence . This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management . Trial registration Clinical Trials.gov identifier : NCT02170883 ; date of registration : 19 June 2014 Background In children with asthma , web-based monitoring and inflammation-driven therapy may lead to improved asthma control and reduction in medications . However , the cost-effectiveness of these monitoring strategies is yet unknown . Objective We assessed the cost-effectiveness of web-based monthly monitoring and of 4-monthly monitoring of FENO as compared with st and ard care . Methods An economic evaluation was performed alongside a r and omised controlled multicentre trial with a 1-year follow-up . Two hundred and seventy-two children with asthma , aged 4–18 years , were r and omised to one of three strategies . In st and ard care , treatment was adapted according to Asthma Control Test ( ACT ) at 4-monthly visits , in the web-based strategy also according to web-ACT at 1 month intervals , and in the FENO-based strategy according to ACT and FENO at 4-monthly visits . Outcome measures were patient utilities , healthcare costs , societal costs and incremental cost per quality -adjusted life year ( QALY ) gained . Results No statistically significant differences were found in QALYs and costs between the three strategies . The web-based strategy had 77 % chance of being most cost-effective from a healthcare perspective at a willingness to pay a generally accepted € 40 000/QALY . The FENO-based strategy had 83 % chance of being most cost-effective at € 40 000/QALY from a societal perspective . Conclusions Economically , web-based monitoring was preferred from a healthcare perspective , while the FENO-based strategy was preferred from a societal perspective , although in QALYs and costs no statistically significant changes were found as compared with st and ard care . As clinical outcomes also favoured the web-based and FENO-based strategies , these strategies may be useful additions to st and ard care . Trial registration number Netherl and s Trial Register ( NTR1995 ) Background Asthma guidelines recommend monitoring of asthma control . However , in a substantial proportion of children , asthma is poorly controlled and the best monitoring strategy is not known . Objectives We studied two monitoring strategies for their ability to improve asthma outcomes in comparison with st and ard care ( SC ) : web-based monthly monitoring with the ( Childhood ) Asthma Control Test ( ACT or C-ACT ) and 4-monthly monitoring of FENO . Methods In this r and omised controlled , partly blinded , parallel group multicentre trial with a 1-year follow-up , children aged 4–18 years with a doctor 's diagnosis of asthma treated in seven hospitals were r and omised to one of the three groups . In the web group , treatment was adapted according to ACT obtained via a website at 1-month intervals ; in the FENO group according to ACT and FENO , and in the SC group according to the ACT at 4-monthly visits . The primary endpoint was the change from baseline in the proportion of symptom-free days ( SFD ) . Results Two-hundred and eighty children ( mean age 10.4 years , 66 % boys ) were included ; 268 completed the study . Mean changes from baseline in SFD were similar between the groups : −2.1 % ( web group , n=90 ) , + 8.9 % ( FENO group , n=91 ) versus 0.15 % ( SC , n=87 ) , p=0.15 and p=0.78 . Daily dose of inhaled corticosteroids ( ICS ) decreased more in the web-based group compared with both other groups ( −200 μg/day , p<0.01 ) , while ACT and SFD remained similar . Conclusions The change from baseline in SFD did not differ between monitoring strategies . With web-based ACT monitoring , ICS could be reduced substantially while control was maintained . Trial registration number NTR 1995 OBJECTIVES . Parents and children often overreport adherence to treatment regimens , which in turn complicates interpretation and application of clinical trial findings . The objective of this investigation was to test the effect of reporting mode on accuracy of inhaled corticosteroid-adherence reporting in children with asthma and their parents under conditions similar to those of an asthma clinical trial . PATIENTS AND METHODS . Participants included 104 children who were being treated with an inhaled corticosteroid delivered by a metered-dose inhaler for asthma diagnosed by their health care provider . Each parent and child dyad was r and omly assigned to 1 of 3 self-report adherence- assessment modes : ( 1 ) audio computer-assisted self-interviewing ; ( 2 ) face-to-face interview with study staff ; or ( 3 ) self-administered paper- and -pencil question naire . At the 4 monthly visits , the parent and child were interviewed separately and asked questions about adherence on the previous day and in the past week . Electronic devices were attached to the each participant 's metered-dose inhaler to provide an objective record of actual daily medication activations . RESULTS . Both children and parents greatly overreported their inhaled corticosteroid adherence when queried about either time frame ( 1 day or 1 week ) in any of the 3 interview modes . One of 3 responses reported full adherence when no medication had been taken . Inconsistent with the study hypothesis , discrepancy between self-report and objective ly measured adherence was greatest in the computer-interview condition . In the optimal circumstance where children were interviewed by study staff about their adherence within the previous 24 hours , reported adherence was within the ±25 % accuracy range for only half of the participants . Larger discrepancy scores were observed for both parents and children when reporting by computer or question naire . CONCLUSIONS . Under the best of conditions in this study , accuracy of self-report was insufficient to provide a st and -alone measure of adherence . Verification of treatment adherence by objective measures remains necessary Optimal use of goal - setting strategies in self-management efforts with high-risk individuals with asthma is not well understood . This study aim ed to describe factors associated with goal attainment in an asthma self-management intervention for African American women with asthma and determine whether goal attainment methods proved beneficial to goal achievement and improved asthma outcomes . Data came from 212 African American women in the intervention arm of a r and omized clinical trial evaluating a telephone-based asthma self-management program . Telephone interview data were collected to assess goals and goal attainment methods identified , asthma symptoms , asthma control , and asthma-related quality of life at baseline and 2-year follow-up . Generalized estimating equations were used to assess the long-term impact of goal setting and goal attainment methods on outcomes . The average age of the sample was 42.1 years ( SD = 14.8 ) . Factors associated with goal attainment included higher education ( p < .01 ) and fewer depressive symptoms ( p < .01 ) . Using a goal attainment method also result ed in more goals being achieved over the course of the intervention ( Estimate [ SE ] = 1.25 [ 0.18 ] ; p < .001 ) when adjusted for clinical and demographic factors . Use of and types of goal attainment methods and goals were not found to significantly affect asthma control , quality of life , or frequency of nighttime asthma symptoms at follow-up . Using a method to achieve goals led to greater goal attainment . Goal attainment alone did not translate into improved asthma outcomes in our study sample . Further studies are warranted to assess the challenges of self-management in chronic disease patients with complex health needs and how goal setting and goal attainment methods can be strategically integrated into self-management efforts to improve health endpoints Some children with severe asthma develop frequent exacerbations despite intensive treatment . We sought to assess the outcome ( severe exacerbations and healthcare use , lung function , quality of life and maintenance treatment ) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy . 50 children with severe uncontrolled asthma were enrolled in a 12-month prospect i ve study and were r and omised into two groups : 1 ) treatment managed with daily home spirometry and medical feedback ( HM ) and 2 ) conventional treatment ( CT ) . The children ’s mean age was 10.9 yrs ( 95 % confidence interval 10.2–11.6 ) . 44 children completed the study ( 21 in the HM group and 23 in the CT group ) . The median number of severe exacerbations per patient was 2.0 ( interquartile range 1.0–4.0 ) in the HM group and 3.0 ( 1.0–4.0 ) in the CT group ( p=0.38 with adjustment for age ) . There were no significant differences between the two groups for unscheduled visits ( HM 5.0 ( 3.0–7.0 ) , CT 3.0 ( 2.0–7.0 ) ; p=0.30 ) , lung function ( pre-&bgr;2-agonist forced expiratory volume in 1 s ( FEV1 ) p=0.13 ) , Paediatric Asthma Quality of Life Question naire scores ( p=0.61 ) and median daily dose of inhaled corticosteroids ( p=0.86 ) . A treatment strategy based on daily FEV1 monitoring with medical feedback did not reduce severe asthma exacerbations Background Telehealth has the potential to improve asthma management through regular monitoring of lung function and /or asthma symptoms by health professionals in conjunction with feedback to patients . Although the benefits of telehealth for improving asthma management have been extensively studied , the feasibility of telehealth for supporting asthma management in pregnant women has not been investigated . This study aims to evaluate the use of telehealth for remotely monitoring lung function and optimising asthma control during pregnancy . Methods A r and omised controlled trial comparing usual care with a telehealth program ( MASTERY © ) has been conducted . The intervention comprised a mobile application – Breathe-easy © supported by a Bluetooth-enabled h and held device ( COPD -6 ® ) , which was used for self-monitoring of lung function ( FEV1 , FEV6 ) twice daily , and recording asthma symptoms and medication usage weekly ; and a written asthma action plan ( WAAP ) . The primary outcome measure is change in asthma control measured using the Asthma Control Question naire ( ACQ ) . Secondary outcomes include changes in mini-Asthma Quality of Life Question naire ( mAQLQ ) score , lung function , asthma-related health visits , days off work/ study , and oral corticosteroid use . Outcome data were collected at baseline , 3 months and 6 months by a research assistant masked to group allocation . Maternal and neonatal outcomes were also collected post-partum . Discussion This is the first study to evaluate the application of telehealth to optimize asthma management in pregnant women . If effective , this telehealth program could improve asthma self-management by pregnant women which may reduce the maternal and fetal risks of poorly controlled asthma during pregnancy . Trial registration Australian New Zeal and Clinical Trials Registry ( ACTRN 12613000800729 ) 17 July Background The financial costs associated with asthma care continue to increase while care remains suboptimal . Promoting optimal self-management , including the use of asthma action plans , along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally . Despite evidence of benefit , guided self-management remains underused , however the potential for online re sources to promote self-management behaviors is gaining increasing recognition . The aim of this paper is to describe the protocol for a pilot evaluation of a website ‘ Living well with asthma ’ which has been developed with the aim of promoting self-management behaviors shown to improve outcomes . Methods / Design The study is a parallel r and omized controlled trial , where adults with asthma are r and omly assigned to either access to the website for 12 weeks , or usual asthma care for 12 weeks ( followed by access to the website if desired ) . Individuals are included if they are over 16-years-old , have a diagnosis of asthma with an Asthma Control Question naire ( ACQ ) score of greater than , or equal to 1 , and have access to the internet . Primary outcomes for this evaluation include recruitment and retention rates , changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Question naire ( AQLQ ) scores , and quantitative data describing website usage ( number of times logged on , length of time logged on , number of times individual pages looked at , and for how long ) . Secondary outcomes include clinical outcomes ( medication use , health services use , lung function ) and patient reported outcomes ( including adherence , patient activation measures , and health status ) . Discussion Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale r and omized controlled trial to successfully recruit and be able to report on necessary outcomes . Here we will provide results across a range of outcomes which will provide estimates of efficacy to inform the design of a future full-scale r and omized controlled trial of the ‘ Living well with asthma ’ website . Trial registration This trial is registered with Current Controlled Trials IS RCT N78556552 on 18/06/13 Background Among adults in the United States , asthma prevalence is disproportionately high among African American women ; this group also experiences the highest levels of asthma-linked mortality and asthma-related health care utilization . Factors linked to biological sex ( e.g. , hormonal fluctuations ) , gender roles ( e.g. , exposure to certain triggers ) and race ( e.g. , inadequate access to care ) all contribute to the excess asthma burden in this group , and also shape the context within which African American women manage their condition . No prior interventions for improving asthma self-management have specifically targeted this vulnerable group of asthma patients . The current study aims to evaluate the efficacy of a culturally- and gender-relevant asthma-management intervention among African American women . Methods / Design A r and omized controlled trial will be used to compare a five-session asthma-management intervention with usual care . This intervention is delivered over the telephone by a trained health educator . Intervention content is informed by the principles of self-regulation for disease management , and all program activities and material s are design ed to be responsive to the specific needs of African American women . We will recruit 420 female participants who self-identify as African American , and who have seen a clinician for persistent asthma in the last year . Half of these will receive the intervention . The primary outcomes , upon which the target sample size is based , are number of asthma-related emergency department visits and overnight hospitalizations in the last 12 months . We will also assess the effect of the intervention on asthma symptoms and asthma-related quality of life . Data will be collected via telephone survey and medical record review at baseline , and 12 and 24 months from baseline . Discussion We seek to decrease asthma-related health care utilization and improve asthma-related quality of life in African American women with asthma , by offering them a culturally- and gender-relevant program to enhance asthma management . The results of this study will provide important information about the feasibility and value of this program in helping to address persistent racial and gender disparities in asthma outcomes .Trial Registration Clinical Trials.gov : Objective To evaluate the feasibility of a phase 3 r and omised controlled trial ( RCT ) of a website ( Living Well with Asthma ) to support self-management . Design and setting Phase 2 , parallel group , RCT , participants recruited from 20 general practice s across Glasgow , UK . R and omisation through automated voice response , after baseline data collection , to website access for minimum 12 weeks or usual care . Participants Adults ( age≥16 years ) with physician diagnosed , symptomatic asthma ( Asthma Control Question naire ( ACQ ) score ≥1 ) . People with unstable asthma or other lung disease were excluded . Intervention ‘ Living Well with Asthma ’ is a desktop/laptop compatible interactive website design ed with input from asthma/ behaviour change specialists , and adults with asthma . It aims to support optimal medication management , promote use of action plans , encourage attendance at asthma review s and increase physical activity . Outcome measures Primary outcomes were recruitment/retention , website use , ACQ and mini-Asthma Quality of Life Question naire ( AQLQ ) . Secondary outcomes included patient activation , prescribing , adherence , spirometry , lung inflammation and health service contacts after 12 weeks . Blinding postr and omisation was not possible . Results Recruitment target met . 51 participants r and omised ( 25 intervention group ) . Age range 16–78 years ; 75 % female ; 28 % from most deprived quintile . 45/51 ( 88 % ; 20 intervention group ) followed up . 19 ( 76 % of the intervention group ) used the website , for a mean of 18 min ( range 0–49 ) . 17 went beyond the 2 ‘ core ’ modules . Median number of logins was 1 ( IQR 1–2 , range 0–7 ) . No significant difference in the prespecified primary efficacy measures of ACQ scores ( −0.36 ; 95 % CI −0.96 to 0.23 ; p=0.225 ) , and mini-AQLQ scores ( 0.38 ; −0.13 to 0.89 ; p=0.136 ) . No adverse events . Conclusions Recruitment and retention confirmed feasibility ; trends to improved outcomes suggest use of Living Well with Asthma may improve self-management in adults with asthma and merits further development followed by investigation in a phase 3 trial . Trial registration number IS RCT N78556552 ; Results This study compared results from Internet and written question naires about respiratory symptoms in order to find out if both forms of the survey yielded the same answers . One thous and seventy-one students , ages 13 to 17 , were asked to complete either an Internet or a written question naire . The demographic characteristics of the participants equalled those of the general Dutch adolescent population . Participants were r and omly assigned to fill out an electronic or written question naire . In addition to eight items from the International Study of Asthma and Allergies in Childhood ( ISAAC ) question naire , two items on doctor visits ( medical attention ) regarding asthma or allergic disease during the past 12 months were included . The participation rate was 87 % . The Internet version of the question naire showed fewer missing answers than the written version , but this was not statistically significant . The respiratory items did not show statistically significant score differences between the Internet and written modes of administration , and there was no visible trend for higher respectively lower scores by either mode of question naire administration . From these results , we conclude that respiratory question naires may be provided to adolescents electronically rather than on paper , since both approaches yielded equal results . To generalize these findings , we recommend repeated studies in other setting Background Effectiveness of Internet-based self-management in patients with asthma has been shown , but its cost-effectiveness is unknown . We conducted a cost-effectiveness analysis of Internet-based asthma self-management compared with usual care . Methodology and Principal Findings Cost-effectiveness analysis alongside a r and omized controlled trial , with 12 months follow-up . Patients were aged 18 to 50 year and had physician diagnosed asthma . The Internet-based self-management program involved weekly on-line monitoring of asthma control with self-treatment advice , remote Web communications , and Internet-based information . We determined quality adjusted life years ( QALYs ) as measured by the EuroQol-5D and costs for health care use and absenteeism . We performed a detailed cost price analysis for the primary intervention . QALYs did not statistically significantly differ between the Internet group and usual care : difference 0.024 ( 95 % CI , −0.016 to 0.065 ) . Costs of the Internet-based intervention were $ 254 ( 95 % CI , $ 243 to $ 265 ) during the period of 1 year . From a societal perspective , the cost difference was $ 641 ( 95 % CI , $ −1957 to $ 3240 ) . From a health care perspective , the cost difference was $ 37 ( 95 % CI , $ −874 to $ 950 ) . At a willingness-to-pay of $ 50000 per QALY , the probability that Internet-based self-management was cost-effective compared to usual care was 62 % and 82 % from a societal and health care perspective , respectively . Conclusions Internet-based self-management of asthma can be as effective as current asthma care and costs are similar . Trial Registration Current Controlled Trials IS RCT The self-management of asthma can improve clinical outcomes . Recently , mobile telephones have been widely used as an efficient , instant personal communication tool . This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme . This was a prospect i ve , controlled study in outpatient clinics . From 120 consecutive patients with moderate-to-severe persistent asthma , 89 were eventually recruited for the study , with 43 in the mobile telephone group ( with a mobile telephone-based interactive asthma self-care system ) . In the mobile telephone group , mean±sem peak expiratory flow rate significantly increased at 4 ( 378.2±9.3 L·min−1 ; n = 43 ; p = 0.020 ) , 5 ( 378.2±9.2 L·min−1 ; n = 43 ; p = 0.008 ) and 6 months ( 382.7±8.6 L·min−1 ; n = 43 ; p = 0.001 ) compared to the control group . Mean±sem forced expiratory volume in 1 s significantly increased at 6 months ( 65.2±3.2 % predicted ; n = 43 ; p<0.05 ) . Patients in the mobile telephone group had better quality of life after 3 months , as determined using the Short Form-12 ® physical component score , and fewer episodes of exacerbation and unscheduled visits than the control group . Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group . The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma , and improves asthma control To determine whether a clinical decision support system can favorably impact the delivery of emergency department and hospital services . R and omized clinical trial of three clinical decision support delivery modalities : email messages to care managers ( email ) , printed reports to clinic administrators ( report ) and letters to patients ( letter ) conducted among 20,180 Medicaid beneficiaries in Durham County , North Carolina with follow-up through 9 months . Patients in the email group had fewer low-severity emergency department encounters vs. controls ( 8.1 vs. 10.6/100 enrollees , p < 0.001 ) with no increase in outpatient encounters or medical costs . Patients in the letter group had more outpatient encounters and greater outpatient and total medical costs . There were no treatment-related differences for patients in the reports group . Among patients < 18 years , those in the email group had fewer low severity ( 7.6 vs. 10.6/100 enrollees , p < 0.001 ) and total emergency department encounters ( 18.3 vs. 23.5/100 enrollees , p < 0.001 ) , and lower emergency department ( $ 63 vs. $ 89 , p = 0.002 ) and total medical costs ( $ 1,736 vs. $ 2,207 , p = 0.009 ) . Patients who were ≥18 years in the letter group had greater outpatient medical costs . There were no intervention-related differences in patient-reported assessment s of quality of life and medical care received . The effectiveness of clinical decision support messaging depended upon the delivery modality and patient age . Health IT interventions must be carefully evaluated to ensure that the result ant outcomes are aligned with expectations as interventions can have differing effects on clinical and economic outcomes Background Long-term asthma management falls short of the goals set by international guidelines . The Internet is proposed as an attractive medium to support guided self-management in asthma . Recently , in a multicenter , pragmatic r and omized controlled parallel trial with a follow-up period of 1 year , patients were allocated Internet-based self-management ( IBSM ) support ( Internet group [ IG ] ) or usual care ( UC ) alone . IBSM support was automatically terminated after 12 months of follow-up . In this study , IBSM support has been demonstrated to improve asthma-related quality of life , asthma control , lung function , and the number of symptom-free days as compared to UC . IBSM support was based on known key components for effective self-management and included weekly asthma control monitoring and treatment advice , online and group education , and communication ( both online and offline ) with a respiratory nurse . Objective The objective of the study was to assess the long-term effects of providing patients 1 year of IBSM support as compared to UC alone . Methods Two hundred adults with physician-diagnosed asthma ( 3 or more months of inhaled corticosteroids prescribed in the past year ) from 37 general practice s and 1 academic outpatient department who previously participated were invited by letter for additional follow-up at 1.5 years after finishing the study . The Asthma Control Question naire ( ACQ ) and the Asthma Quality of Life Question naire ( AQLQ ) were completed by 107 participants ( 60 UC participants and 47 IG participants ) . A minimal clinical important difference in both question naires is 0.5 on a 7-point scale . Results At 30 months after baseline , a sustained and significant difference in terms of asthma-related quality of life of 0.29 ( 95 % CI 0.01 - 0.57 ) and asthma control of -0.33 ( 95 % CI -0.61 to -0.05 ) was found in favor of the IBSM group . No such differences were found for inhaled corticosteroid dosage or for lung function , measured as forced expiratory volume in 1 second . Conclusions Improvements in asthma-related quality of life and asthma control were sustained in patients who received IBSM support for 1 year , even up to 1.5 years after terminating support . Future research should be focused on implementation of IBSM on a wider scale within routine asthma care . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 79864465 ; http://www.controlled-trials.com/IS RCT N79864465 ( Archived by WebCite at http://www.webcitation.org/6J4VHhPk4 ) BACKGROUND Asthma is an important cause of morbidity , absence from school , and use of health services among children . Computer-based educational programs can be design ed to enhance children 's self-management skills and to reduce adverse outcomes . OBJECTIVE To assess the effectiveness of an interactive device programmed for the management of pediatric asthma . DESIGN A r and omized controlled trial ( 66 participants were in the intervention group and 68 were in the control group ) . SETTING Interventions conducted at home and in an outpatient hospital clinic . PARTICIPANTS Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician . INTERVENTION An asthma self-management and education program , the Health Buddy , design ed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers ( physicians , nurses , or other case managers ) through a secure Web site . Control group participants used an asthma diary . MAIN OUTCOME MEASURES Any limitation in activity was the primary outcome . Secondary outcomes included perceived asthma symptoms , absence from school , any peak flow reading in the yellow or red zone , and use of health services . RESULTS After adjusting for covariates , the odds of having any limitation in activity during the 90-day trial were significantly ( P = .03 ) lower for children r and omized to the Health Buddy . The intervention group also was significantly ( P = .01 ) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital ( P = .05 ) . Self-care behaviors , which were important correlates of asthma outcomes , also improved far more for the intervention group . CONCLUSION Compared with the asthma diary , monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence . In a prospect i ve , multicenter , interventional clinical trial with parallel groups , asthmatics were r and omized into an intervention group or a control group . Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization . After that , biweekly telephone calls were made to promote treatment adherence . Asthmatics included in the control group received only the initial and final telephone calls . Both groups received three packages of salmeterol/fluticasone for 3 months . The main outcome measure was the percentage of participants who took the prescribed doses of the drug . A total of 271 patients were included . The overall adherence rate was 51.9 % for the control group and 74.3 % for the intervention group . This meant a reduction of relative risk ( RRR ) of 47 % ( p < 0.001 ) . The number needed to treat ( NNT ) was 4.5 . The only variable associated with better adherence was severe persistent asthma . A low-cost easily implemented intervention , tailored to each individual , enhanced the adherence rate among Brazilian asthmatic patients OBJECTIVE To test the feasibility and preliminary effectiveness of the School-Based Preventive Asthma Care Technology ( SB-PACT ) program , which includes directly observed therapy of preventive asthma medications in school facilitated by Web-based technology for systematic symptom screening , electronic report generation , and medication authorization from providers . STUDY DESIGN We conducted a pilot r and omized trial of SB-PACT versus usual care with 100 children ( aged 3 - 10 years ) from 19 inner-city schools in Rochester , New York . Outcomes were assessed longitudinally by blinded interviewers . Analyses included bivariate statistics and linear regression models , adjusting for baseline symptoms . RESULTS There were data for 99 subjects for analysis . We screened all children using the Web-based system , and 44 of 49 treatment group children received directly observed therapy as authorized by their providers . Treatment group children received preventive medications 98 % of the time they were in school . Over the school year , children in the treatment group experienced nearly 1 additional symptom-free day over 2 weeks versus the usual care group ( 11.33 vs 10.40 , P = .13 ) . Treatment children also experienced fewer nights with symptoms ( 1.68 vs 2.20 , P = .02 ) , days requiring rescue medications ( 1.66 vs 2.44 , P = .01 ) , and days absent from school due to asthma ( 0.37 vs 0.85 , P = .03 ) compared with usual care . Further , treatment children had a greater decrease in exhaled nitric oxide ( -9.62 vs -0.39 , P = .03 ) , suggesting reduction in airway inflammation . CONCLUSION The SB-PACT intervention demonstrated feasibility and improved outcomes across multiple measures in this pilot study . Future work will focus on further integration of preventive care delivery across community and primary care systems OBJECTIVES To evaluate a self-regulation intervention for asthma for older adults . DESIGN A blinded r and omized controlled trial . SETTING Single-center tertiary care academic center . PARTICIPANTS Seventy older adults aged 65 and older with persistent asthma r and omized to an intervention or control group . INTERVENTION Participants participate in a six-session program conducted over the telephone and in group sessions . Participants selected an asthma-specific goal , identified problems , and addressed potential barriers . MEASUREMENTS Outcomes were assessed at 1 , 6 , and 12 months and included the mini-Asthma Quality of Life Question naire ( mAQLQ ) , Asthma Control Question naire ( ACQ ) , healthcare utilization , exhaled nitric oxide ( FENO ) , and percentage of predicted forced expiratory volume in 1 second ( FEV1 % ) . RESULTS The mAQLQ score was significantly higher in the intervention group at 1 , 6 , and 12 months , even after controlling for confounding factors . The between-group difference decreased over time , although at 12 months , it remained greater than 0.5 points . The ACQ was better in the intervention group than in the control group at 1 , 6 , and 12 months . At 12 months , those in the intervention group were 4.2 times as likely as those in the control group to have an ACQ score in the controlled range . Healthcare utilization was lower in the intervention group , although no difference was observed in FENO or predicted FEV1 % . CONCLUSION A self-regulation intervention can improve asthma control , quality of life , and healthcare utilization in older adults Asthma morbidity is high among inner-city minority adults . Improving access to care and patient-provider communication are believed to be essential for improving outcomes . Access and communication in turn increasingly rely on information technology including features of the Electronic Health Record . Its patient portal offers web-based communication with providers and practice s. How patients with limited re sources and educational opportunities can benefit from this portal is unclear . In contrast , home visits by community health workers ( CHWs ) have improved access to care for asthmatic children and promoted caretaker-clinician communication . We describe the planning , design , and methodology of an ongoing r and omized controlled trial for 300 adults , predominantly African American and Hispanic/Latino , with uncontrolled asthma recruited from low income urban neighborhoods who are directed to the most convenient internet access and taught to use the portal , with and without home visits from a CHW . The study 1 ) compares the effects of the 1-year interventions on asthma outcomes ( improved asthma control , quality of life ; fewer ED visits and hospitalizations for asthma or any cause ) , 2 ) evaluates whether communication ( portal use ) and access ( appointments made/kept ) mediate the interventions ' effects on asthma outcomes , and 3 ) investigates effect modification by literacy level , primary language , and convenience of internet access . In home visits , CHWs 1 ) train patients to competency in portal use , 2 ) enhance care coordination , 3 ) communicate the complex social circumstances of patients ' lives to providers , and 4 ) compensate for differences in patients ' health literacy skills . The practical challenges to design and implementation in the targeted population are presented CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits OBJECTIVE . The purpose of this study was to evaluate the impact and acceptability of an educational multimedia program design ed to promote self-management skills in children with asthma . METHODS . We conducted a r and omized , controlled trial with measures at baseline and 1- and 6-month follow-up . The trial was conducted in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals . Participants included 101 children aged 7 to 14 years under the care of hospital-based asthma services . The children were r and omly assigned to receive an asthma information booklet alone or the booklet plus The Asthma Files , an interactive CD-ROM for children with asthma . Asthma knowledge was the primary outcome measure . Other measures included asthma locus of control , lung function , use of oral steroids , and school absence . RESULTS . At the 1-month follow-up ( n = 99 ) , children in the computer group had improved knowledge compared with the control group and a more internal locus of control . There were no differences in objective lung-function measures , hospitalizations , or oral steroid use . The study participants were positive in their evaluation of the intervention . At the 6-month follow-up ( n = 90 ) , significantly fewer children in the intervention group had required oral steroids and had had time off school for asthma in the previous 6 months . The difference did not reach statistical significance in the intention-to-treat analysis for both steroid use and school absence . CONCLUSION . The Asthma Files was found to be an effective and popular health education tool for promoting asthma self-management skills within pediatric care Long recognizing that asthma , one of the most common chronic childhood diseases , is difficult to manage , the National Asthma Education Prevention Program developed clinical practice guidelines to assist health care providers , particularly those in the primary care setting . Yet , maintenance asthma care still fails to meet national st and ards . Therefore , in an attempt to improve and support asthma self-management behaviors for parents of children 5 to 12 years of age with persistent asthma , a novel nurse telephone coaching intervention was tested in a r and omized , controlled trial . A detailed description of the intervention is provided along with parent satisfaction results , an overview of the training used to prepare the nurses , and a discussion of the challenges experienced and lessons learned Objective : This study was conducted to test the effectiveness of a theory-based interactive voice response ( IVR ) intervention to improve adherence to controller medications among adults with asthma . Methods : Fifty participants aged 18 to 65 years who had a physician diagnosis of asthma and a prescription for a daily inhaled corticosteroid , attended a baseline visit and a final visit 10 weeks later . Participants r and omized to the intervention group received 2 automated IVR telephone calls separated by one month , with one additional call if they reported recent symptoms of poorly controlled disease or failure to fill a prescription . Calls were completed in less than 5 minutes and included content design ed to inquire about asthma symptoms , deliver core educational messages , encourage refilling of inhaled corticosteroid prescriptions , and increase communication with providers . Adherence was tracked during 10 weeks , with objective measures that included either electronic monitors or calculation of canister weight . Participants completed the Asthma Quality of Life Question naire , the Asthma Control Test , and the Beliefs in Medications Question naire ( BMQ ) during both visits . Results : Adherence was 32 % higher among patients in the IVR group than those in the control group ( P = .003 ) . A more favorable shift in perception of inhaled corticosteroids was seen on BMQ scores of patients in the IVR group ( P = .003 ) , which in turn correlated with degree of adherence change ( r = 0.342 ; P = .0152 ) . No differences emerged for the Asthma Quality of Life Question naire or Asthma Control Test . Conclusions : The IVR intervention result ed in a significant increase in adherence to inhaled corticosteroid treatment and improved BMQ scores during the study interval . The association of increased adherence with increased BMQ scores suggests that the intervention succeeded in helping participants adopt a more favorable perception of their controller medication , leading in turn to improved adherence INTRODUCTION Asthma control often is poor in adolescents and this causes considerable morbidity . Internet-based self-management ( IBSM ) improves asthma-related quality of life in adults . We hypothesized that IBSM improves asthma-related quality of life in adolescents . METHODS Adolescents ( 12 - 18 years ) with persistent and not well-controlled asthma participated in a r and omized controlled trial with 1 year follow-up and were allocated to IBSM ( n = 46 ) or usual care ( UC , n = 44 ) . IBSM consisted of weekly asthma control monitoring with treatment advice by a web-based algorithm . Outcomes included asthma-related quality of life ( Pediatric Asthma Quality of Life Question naire , PAQLQ ) and asthma control ( Asthma Control Question naire , ACQ ) and were analyzed by a linear mixed-effects model . RESULTS At 3 months , PAQLQ improved with 0.40 points ( 95 % CI : 0.17 - 0.62 , P < 0.01 ) , by IBSM compared to 0.0 points for UC ( P = 0.02 for the difference ) . At 12 months the between-group difference was -0.05 ( 95 % CI : -0.50 to 0.41 , P = 0.85 ) . At 3 months ACQ improved more in IBSM than in UC ( difference : -0.32 points ; 95 % CI : -0.56 to -0.079 , P < 0.01 ) . At 12 months the difference was -0.05 ( 95 % CI : -0.35 to 0.25 , P = 0.75 ) . CONCLUSION IBSM improved asthma-related quality of life and asthma control in adolescents with not well-controlled asthma after 3 months , but not after 12 months BACKGROUND Self management programs have been advocated for adults who have recently been admitted to hospital or have recently attended an emergency department because of asthma . A new telephone based approach has already been trialled for the management of a number of other chronic conditions . This study sought to determine the effect of a telephone based asthma management program for adults with asthma . METHODS Adults with one or more previous admissions for asthma to either or both of two tertiary hospitals between 1 May 2001 and 30 November 2003 were invited to participate . All participants received one face-to-face session with an asthma educator . Participants were r and omised to intervention ( six telephone calls over 6 months ) or control ( usual care ) groups . Measures of health care utilisation and morbidity were collected weekly for 12 months . RESULTS Seventy-one adults ( 54 females ) with a mean age of 36.2 years were recruited to the study . Twenty hospital re-admissions were recorded for the control group and one for the intervention group at 12 months . Re-admission was significantly associated with allocation to control group ( p=0.05 ) . The control group was significantly more likely to report being woken by asthma on more than half the nights of the week ( p=0.03 ) . DISCUSSION Telephone based self management intervention results in clinical ly important reductions in hospital re-admission in adults previously hospitalised with asthma BACKGROUND Experience from other fields of internal medicine shows that Internet-based technology can be used to monitor various diseases . The new technology h and les complex calculation programs easily , and it is a unique way of communicating . These advantages might be used in optimizing the treatment for asthmatic subjects because undertreatment is a common problem found in European asthmatic subjects . OBJECTIVE We sought to investigate the outcome of monitoring and treatment using a physician-managed online interactive asthma monitoring tool and to assess whether the outcome differs from that of monitoring and treatment in an outpatient respiratory clinic or in primary care . METHODS Three hundred asthmatic subjects were r and omized to 3 parallel groups in a 6-month prospect i ve study : ( 1 ) Internet-based monitoring ( n = 100 ) ; ( 2 ) specialist monitoring ( n = 100 ) ; and ( 3 ) general practitioner ( GP ) monitoring ( n = 100 ) . All the patients were examined on entry into the study and after 6 months of treatment . RESULTS The treatment and monitoring with the Internet-based management tool lead to significantly better improvement in the Internet group than in the other 2 groups regarding asthma symptoms ( Internet vs specialist : odds ratio of 2.64 , P = .002 ; Internet vs GP : odds ratio of 3.26 ; P < .001 ) , quality of life ( Internet vs specialist : odds ratio of 2.21 , P = .03 ; Internet vs GP : odds ratio of 2.10 , P = .04 ) , lung function ( Internet vs specialist : odds ratio of 3.26 , P = .002 ; Internet vs GP : odds ratio of 4.86 , P < .001 ) , and airway responsiveness ( Internet vs GP : odds ratio of 3.06 , P = .02 ) . CONCLUSION When physicians and patients used an interactive Internet-based asthma monitoring tool , better asthma control was achieved OBJECTIVE To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization . STUDY DESIGN R and omized clinical trial . METHODS Patients with persistent asthma were r and omly assigned to telephone outreach ( automated = 3389 , live caller = 192 ) or usual care ( n = 3367 ) . Intervention participants received 3 outreach calls over a 10-month period . The intervention provided brief , supportive information and flagged individuals with poor asthma control for follow-up by a provider . A survey was mailed to 792 intervention participants and 236 providers after the intervention . Additional feedback was obtained as part of the final intervention contact . RESULTS The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use , healthcare utilization , asthma control , or quality of life . Post hoc analyses found that , compared with the control group , individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists . They also reported higher satisfaction with their asthma care and better asthma-specific quality of life . Of surveyed providers , 59 % stated the program helped them to clinical ly manage their asthma patients and 70 % thought the program should be continued . CONCLUSIONS This study did not find improved health outcomes in the primary analyses . The intervention was well accepted by providers , however , and the individuals who participated in the calls appeared to have benefited from them . These findings suggest that further studies of automated telephone outreach interventions seem warranted BACKGROUND Guided self-management is an important component of asthma care . Most trials have evaluated paper-based strategies . The effectiveness of new communication technologies remains uncertain . OBJECTIVES To compare the feasibility and clinical outcomes of a st and ard paper-based asthma self-management strategy with web-based strategies . METHODS In a crossover trial , 21 patients using inhaled corticosteroids and long-acting B2-agonists ( mean [ SD ] age 29 [ 10 ] years ) were r and omly assigned to use a sequence of web-based and paper-based diary and action plan . Quality of life , asthma control , lung function , and airway inflammation were assessed using the Asthma Life Quality Question naire ( ALQ ) , Asthma Control Question naire ( ACQ-5 ) , Mini Asthma Quality of Life Question naire ( Mini AQLQ ) , and office spirometry . The ratio of forced expiratory volume in the first second of expiration ( FEV1 ) to peak expiratory flow ( PEF ) rate ( PiKo-1 ) and fraction of exhaled nitric oxide ( FE(NO ) ) were monitored . The main clinical outcomes were asthma control and FE(NO ) . Quality of data and adherence to monitoring tools were the main process outcomes . RESULTS Significant improvements were observed in the AQL and ACQ scores , although lung function did not change . FE(NO ) was significantly reduced only after a web-based strategy but a significant period effect occurred ( P = .006 ) . There were no differences in clinical outcomes between web-based and paper-based management . No intervention-related adverse effects were observed . Adherence seemed higher with the paper-based strategy ( P < .001 ) . However , paper data were unreliable when compared to automatic daily electronic FEV1/PEF records . Twelve patients were very interested in continuing self-management with the web-based approach compared with 2 in using paper tools ( P = .002 ) . CONCLUSIONS Web-based management was feasible , safe , and preferred by patients . Short-term outcomes were at least as good , and data quality was improved Asthma prevalence is increasing among poor and minority children . We examined the effectiveness of a novel interactive device programmed for self-management of pediatric asthma in reducing asthma control problems and hospitalizations . A r and omized controlled trial ( 66 children in the intervention group and 68 in the control group ) was conducted at home and in an outpatient hospital clinic with 8 - 16-year-old inner-city children with physician-diagnosed asthma . During a 12-week period , children in the experimental group received an asthma self-management and education program , the Health Buddy ( Health Hero Network ) , design ed to enable them to monitor their symptoms and transmit this information to a case manager through a secure website . Control group participants used an asthma diary . After adjusting for baseline asthma control problems , asthma severity , and seasonality , children r and omized to automated self-management had a significantly lower mean number of asthma control problems at 6 weeks ( 2.0 , SD = 1.6 ) as compared to children assigned to the asthma diary ( 2.7 , SD = 1.6 ) ( p = 0.03 ) . By 12 weeks , after adjusting for time and the other covariates , asthma control problems dropped markedly in both groups , and did not differ by intervention modality ( p = .07 ) . The intervention modality was not a significant predictor of hospitalization . Educational interventions that encourage children 's active involvement in their own care and symptom monitoring would help children increase their control of asthma problems . Compared to the asthma diary , the automated self-management had a significant short-term impact on asthma control problems . Its initial effectiveness and more consistent use suggest that remote monitoring may be successfully used in short-term interventions and in setting s where staffing for case management is weak We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma , whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians . We examined the effectiveness of this system with a r and omized control study . Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and r and omly assigned to either the tele-medicine or control group . After six months of participation in the program , the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group . Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow ( PEF ) value successfully , and at six months had noticed an improvement in PEF . We therefore conclude that the system effectively contributes to the management of poorly controlled asthma . In addition , further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously BACKGROUND There is a high non-attendance rate for traditional clinic-based routine asthma care in general practice . Alternative methods of providing routine asthma care need to be examined . AIM To examine the cost and effectiveness of targeted routine asthma care in general practice using telephone triage , compared to usual clinic care . DESIGN OF STUDY An open r and omised controlled trial . SETTING A single semi-rural practice in the southwest of Engl and . METHOD Adult patients with asthma were r and omised to receive either their routine asthma care in the surgery or care by telephone triage . Asthma control parameters , health status and NHS re source utilisation were measured over the 12-month study period . RESULTS One hundred and ninety-four patients were r and omised and 35 % per cent more patients ( n = 84 versus n = 62 ) received more than one consultation in the telephone group . Asthma control as measured by the asthma control question naire ( ACQ ) was similar in the clinic and telephone groups : mean change in ACQ = -0.11 ( 95 % CI = -0.32 to 0.11 ) versus -0.18 ( 95 % CI = -0.38 to 0.02 ) . Mean NHS costs were 210 pounds sterling per patient per year in the telephone group compared to 334 pounds sterling in the clinic group ( P-value of bootstrapped difference = 0.071 ) . CONCLUSION Targeted routine asthma care by telephone triage of adult asthmatics can lead to more asthma patients being review ed , at less cost per patient and without loss of asthma control compared to usual routine care in the surgery We have evaluated the feasibility of using the mobile phone short message service ( SMS ) for symptom monitoring in patients with asthma . All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrolment ( n = 497 ) . Those meeting the inclusion criteria were r and omized into a control ( n = 60 ) and intervention group ( n = 60 ) . Patients in the intervention group received SMS messages according to a structured workflow , while patients in the control group had no SMS support . In the intervention group , the mean response rate to the messages was 82 % . There was an improvement in the Asthma Control Test ( ACT ) scores in 36 subjects in the intervention group compared to 28 subjects in the control group . There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group , and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group . However , none of these differences were significant . There was no reduction in admission rates in either group ( P = 0.5 ) . The service was accepted by most patients , but its long-term effectiveness on the management of asthma remains to be determined Methods We conducted an open-label r and omized controlled trial to investigate the impact of support intervention to the outcome of parents of asthmatic children . The constructed supporting program includes scheduled one-by-one and group asthma knowledge education , treatment adherence reinforcement , family support course , and telephone follow-up . The differences of parental knowledge of asthma , medication adherence , hospital re-admission , and health care re source usage between two groups were compared This pilot clinical investigation was conducted to compare a home therapeutic drug-monitoring ( TDM ) method for theophylline blood levels and a traditional TDM method with respect to various patient outcome factors . Out patients with chronic obstructive pulmonary diseases ( COPD ) or asthma who were receiving long-term theophylline therapy were r and omized to one of two groups : home TDM or traditional TDM ( controls ) . Patients in the former group monitored their serum theophylline levels at home over 6 months . Patients in both groups completed survey instruments , including question naires , visual analog scales , and other psychosocial measures , at design ated times throughout the study period . Pulmonary function tests and dyspnea index scores were evaluated at each clinic visit . Results indicated a significantly lower ( p less than 0.05 ) number of changes in concomitant drug therapy in the home TDM group compared with controls . Other indicators that showed a trend toward more favorable outcomes in the home TDM group included symptomology , percentage of levels within the therapeutic range , patient attitudes regarding participation in health care management , and pulmonary function test results . Home monitoring prevented unnecessary clinic visits in several instances when theophylline dosage adjustments were based on telephone reports from patients . The utility of a home TDM method for theophylline has not been reported previously despite potential for broad applications . Findings from this preliminary study may support the use and feasibility of state-of-the-art method ologies in carefully selected sub population s outside the confines of the hospital or clinic setting BACKGROUND Only about a third of people with asthma attend an annual review . Clinicians need to identify cost-effective ways to improve access and ensure regular review . AIM To compare the cost-effectiveness of nurse-led telephone with face-to-face asthma review s. DESIGN OF STUDY Cost-effectiveness analysis based on a 3-month r and omised controlled trial . SETTING Four general practice s in Engl and . METHOD Adults due an asthma review were r and omised to telephone or face-to-face consultations . Trial nurses recorded proportion review ed , duration of consultation , and abortive calls/missed appointments . Data on use of healthcare re sources were extracted from GP records . Cost-effectiveness was assessed from the health service perspective ; sensitivity analyses were based on proportion review ed and duration of consultation . RESULTS A total of 278 people with asthma were r and omised to surgery ( n = 141 ) or telephone ( n = 137 ) review . Onehundred- and -one ( 74 % ) of those with asthma in the telephone group were review ed versus 68 ( 48 % ) in the surgery group ( P < 0.001 ) . Telephone consultations were significantly shorter ( mean duration telephone = 11.19 minutes [ st and ard deviation { SD } = 4.79 ] versus surgery = 21.87 minutes [ SD = 6.85 ] , P < 0.001 ) . Total respiratory healthcare costs per patient over 3 months were similar ( telephone = pounds sterling 64.49 [ SD = 73.33 ] versus surgery = pounds sterling 59.48 [ SD = 66.02 ] , P = 0.55 ) . Total costs of providing 101 telephone versus 68 face-to-face asthma review s were also similar ( telephone = pounds sterling 725.84 versus surgery = pounds sterling 755.70 ) , but mean cost per consultation achieved was lower in the telephone arm ( telephone = pounds sterling 7.19 [ SD = 2.49 ] versus surgery = pounds sterling 11.11 [ SD = 3.50 ] ; mean difference = - pounds sterling 3.92 [ 95 % confidence interval = - pounds sterling 4.84 to pounds sterling 3.01 ] , P < 0.001 ) . CONCLUSIONS Telephone consultations enable a greater proportion of asthma patients to be review ed at no additional cost to the health service . This mode of delivering care improves access and reduces cost per consultation achieved The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population OBJECTIVE . The goal was to determine whether home asthma telemonitoring with store- and -forward technology improved outcomes , compared with in-person , office-based visits . METHODS . A total of 120 patients , 6 to 17 years of age , with persistent asthma were assigned r and omly to the office-based or virtual group . The 2 groups followed the same ambulatory clinical pathway for 12 months . Office-based group patients received traditional in-person education and case management . Virtual group patients received computers , Internet connections , and in-home , Internet-based case management and received education through the study Web site . Disease control outcome measures included quality of life , utilization of services , and symptom control . RESULTS . A total of 120 volunteers ( 45 female ) were enrolled . The groups were clinical ly comparable ( office-based : 22 female/38 male ; mean age : 9.0 ± 3.0 years ; virtual : 23 female/37 male ; mean age : 10.2 ± 3.1 years ) . Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks ( 94 % vs 89 % ) , had greater adherence to daily asthma symptom diary su bmi ssion ( 35.4 % vs 20.8 % ) , had less participant time ( 636 vs 713 patient-months ) , and were older . Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline . There were no other differences in therapeutic or disease control outcome measures . CONCLUSIONS . Virtual group patients achieved excellent asthma therapeutic and disease control outcomes . Compared with those who received st and ardized office-based care , they were more adherent to diary su bmi ssion and had better inhaler scores at 52 weeks . Store- and -forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma UNLABELLED The use of communication technologies may overcome some of the difficulties of conventional , paper-based , self-management of chronic diseases . This paper aims to describe and evaluate the use of P'ASMA - a web based asthma self-management support tool regarding the opinion of patients and their adherence to monitoring in comparison to st and ard paper-based tools . SYSTEM DESCRIPTION P'ASMA allows the collection of asthma monitoring data and provides , to both patient and doctor , immediate feedback about patient 's condition . For each patient a set of forms and scheduling options can be chosen . EVALUATION METHODS Twenty-one adults with previous medical diagnosis of asthma were included in an exploratory r and omized crossover study . Patients used P'ASMA or a paper asthma diary and action-plan each during 4 weeks in a r and om sequence . RESULTS The number of patients who wrote negative remarks regarding P'ASMA was 2 and regarding paper-tools was 11 ; positive comments were 6 and 1 respectively for P'ASMA and Paper-based . Twelve patients were very interested to continue to monitor their asthma using P'ASMA whereas only 2 with Paper-based ( p=0.002 ) . Of the 19 problems reported with P'ASMA , 9 were related to the Internet connection , 5 to the user interface , 3 to internal system errors and 2 to the questions interpretation . The completeness of paper diary records was better ; however , 10 patients reported filling it several days at once which was not allowed in P'ASMA . CONCLUSIONS The intervention was feasible , safe and the problems detected in the web-application can be corrected . With P'ASMA data quality improved as the integrity features increase the reliability of the data . Moreover , patients preferred the web-based application to monitor their asthma Abstract Objective : To determine whether routine review by telephone of patients with asthma improves access and is a good alternative to face to face review s in general practice s. Design : Pragmatic , r and omised controlled trial . Setting : Four general practice s in Engl and . Participants : 278 adults who had not been review ed in the previous 11 months . Intervention : Participants were r and omised to either telephone review or face to face consultation with the asthma nurse . Main outcome measures : Primary outcome measures were the proportion of participants who were review ed within three months of r and omisation and disease specific quality of life , as measured by the Juniper mini asthma quality of life question naire . Secondary outcome measures included the vali date d “ short Q ” asthma morbidity score , nursing care satisfaction question naire score , and length of consultation . Results : Of 137 people r and omised to telephone consultation , 101 ( 74 % ) were review ed , compared with 68 review ed ( 48 % ) of the 141 people in the surgery group , a difference of 26 % ( 95 % confidence interval 14 % to 37 % ; P<0.001 ; number needed to treat 3.8 ) . Three months after r and omisation the two groups did not differ in the Juniper score ( risk difference −0.07 ( 95 % confidence interval −0.40 to 0.27 ) or in satisfaction with the consultation ( risk difference −0.07 ( −0.27 to 0.13 ) ) . Telephone consultations were on average 10 minutes shorter than review s held in the surgery ( mean difference 10.7 minutes ( 12.6 to 8.8 ; P<0.001 ) ) . Conclusions : Compared with face to face consultations in the surgery , telephone consultations enable more people with asthma to be review ed , without clinical disadvantage or loss of satisfaction . A shorter duration means that telephone consultations are likely to be an efficient option in primary care for routine review of asthma . What is already known on the topic Regular review of patients with asthma reduces morbidity and is endorsed as good practice by UK and international guidelines , but only about a third of patients attend for their annual review Most studies of telephone consultation in primary care have focused on consultations requested by patients rather than their use in the routine review of chronic disease What this study adds Telephone consultations enable more people with asthma to be review ed Telephone consultations are shorter than face to face consultations , without any apparent clinical disadvantage Patients are satisfied with telephone Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p < 0.05 ) and night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p < 0.05 ) . There was no significant difference between the groups in daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up BACKGROUND Women with asthma have greater mortality and morbidity than men in the United States . To date , there has been no rigorous evaluation of an intervention focused on the particular problems in asthma management faced by women . This study was a r and omized clinical trial of a self-regulation , telephone counseling intervention emphasizing women 's concerns , and sex and gender role factors in their management of asthma . METHODS A total of 808 women with diagnosed asthma were r and omly assigned to the intervention group or a usual-care control group , including conventional asthma education . Interviews and medical record data were collected to assess psychosocial factors , and the behavioral factors of functioning , quality of life , symptoms , and health-care use at baseline and the subsequent 1 year . Generalized estimating equations , identity link , logit link , and log link were employed to analyze the data . RESULTS Compared to control subjects , the women receiving treatment had greater annual reductions in the average number of nights with asthma symptoms ( p = 0.04 ) , days of missed work/school ( p = 0.03 ) , emergency department visits ( p = 0.04 ) , unscheduled office visits ( p = 0.01 ) , and scheduled office visits ( p = 0.04 ) . They had greater recognition of asthma symptoms during the menstrual cycle ( p = 0.0003 ) , had decreased asthma symptoms with sexual activity ( p = 0.008 ) , and had greater improvement in quality of life ( p = 0.0005 ) , self-regulation ( p = 0.03 ) , and self-confidence to manage asthma ( p = 0.001 ) . CONCLUSION The intervention improved women 's clinical status , functioning , quality of life , and health-care use . A program with a focus on asthma management problems particular to women can significantly assist female asthma patients Background Asthma is the most common pediatric illness in the United States , burdening low-income and minority families disproportionately and contributing to high health care costs . Clinic-based asthma education and telephone case management have had mixed results on asthma control , as have eHealth programs and online games . Objectives To test the effects of ( 1 ) CHESS+CM , a system for parents and children ages 4–12 years with poorly controlled asthma , on asthma control and medication adherence , and ( 2 ) competence , self-efficacy , and social support as mediators . CHESS+CM included a fully automated eHealth component ( Comprehensive Health Enhancement Support System [ CHESS ] ) plus monthly nurse case management ( CM ) via phone . CHESS , based on self-determination theory , was design ed to improve competence , social support , and intrinsic motivation of parents and children . Methods We identified eligible parent – child dyads from files of managed care organizations in Madison and Milwaukee , Wisconsin , USA , sent them recruitment letters , and r and omly assigned them ( unblinded ) to a control group of treatment as usual plus asthma information or to CHESS+CM . Asthma control was measured by the Asthma Control Question naire ( ACQ ) and self-reported symptom-free days . Medication adherence was a composite of pharmacy refill data and medication taking . Social support , information competence , and self-efficacy were self-assessed in question naires . All data were collected at 0 , 3 , 6 , 9 , and 12 months . Asthma diaries kept during a 3-week run-in period before r and omization provided baseline data . Results Of 305 parent – child dyads enrolled , 301 were r and omly assigned , 153 to the control group and 148 to CHESS+CM . Most parents were female ( 283/301 , 94 % ) , African American ( 150/301 , 49.8 % ) , and had a low income as indicated by child ’s Medicaid status ( 154/301 , 51.2 % ) ; 146 ( 48.5 % ) were single and 96 of 301 ( 31.9 % ) had a high school education or less . Completion rates were 127 of 153 control group dyads ( 83.0 % ) and 132 of 148 CHESS+CM group dyads ( 89.2 % ) . CHESS+CM group children had significantly better asthma control on the ACQ ( d = –0.31 , 95 % confidence limits [ CL ] –0.56 , –0.06 , P = .011 ) , but not as measured by symptom-free days ( d = 0.18 , 95 % CL –0.88 , 1.60 , P = 1.00 ) . The composite adherence scores did not differ significantly between groups ( d = 1.48 % , 95 % CL –8.15 , 11.11 , P = .76 ) . Social support was a significant mediator for CHESS+CM ’s effect on asthma control ( alpha = .200 , P = .01 ; beta = .210 , P = .03 ) . Self-efficacy was not significant ( alpha = .080 , P = .14 ; beta = .476 , P = .01 ) ; neither was information competence ( alpha = .079 , P = .09 ; beta = .063 , P = .64 ) . Conclusions Integrating telephone case management with eHealth benefited pediatric asthma control , though not medication adherence . Improved methods of measuring medication adherence are needed . Social support appears to be more effective than information in improving pediatric asthma control . Trial Registration Clinical trials.gov NCT00214383 ; http:// clinical trials.gov/ct2/show/NCT00214383 ( Archived by WebCite at http://www.webcitation.org/68OVwqMPz RATIONALE , AIMS AND OBJECTIVES The aim of the study was to evaluate the effects on , and the relationship between , asthma symptoms , asthma-specific quality of life and medical consumption of a nurse-led telemonitoring intervention compared with regular care in asthma in the Netherl and s. METHODS One hundred and nine asthmatic out patients ( 56 children ; 53 adults ) were r and omly assigned to the treatment arms ( 12-month follow-up ) . The control group received regular outpatient care , while the intervention group used an asthma monitor with modem at home with an asthma nurse as the main caregiver . Clinical asthma symptoms and medical consumption were measured by using diaries . Asthma-specific quality of life was measured by the ( Paediatric ) Asthma Quality of Life Question naire . RESULTS The study population generally represented mild to moderate asthmatics . The results show improvement in follow-up , but no statistically significant difference between the groups was observed . Moderate to high correlations were found within the outcome parameters , but the most remarkable was the low and statistically significant correlation between asthma-specific quality of life ( daily functioning ) and the self-reported beta-2 agonists . CONCLUSION Overall , the telemonitoring programme evaluated in this study did not significantly decrease asthma symptoms or medical consumption , or improve asthma-specific quality of life . The results showed that a telemonitoring programme on its own is not a guarantee of success . The patients ' perception of asthma-specific quality of life ( daily functioning ) should be a key element in asthma telemonitoring programmes Practical problems and patients or doctors low compliance has been hampering a wider use of self-management in asthma . Mobile or web technologies for supporting selfmanagement may improve patient – doctor communication and patient self-efficacy ( 1 , 2 ) . Furthermore , recent evidence suggests that interactive Internet-based asthma monitoring improves asthma control ( 3 ) . However , patients may not be willing to use a web asthma diary for more than short periods , possibly because it does not fit into their everyday lives ( 4 ) . The use of mobile phones has been suggested to overcome this problem ( 4 , 5 ) , but , to our knowledge , no data are available on the willingness of patients to use mobile phones , and very few data have been reported on their willingness to use the web for asthma self-management ( 6 ) . In the framework of a running r and omized controlled trial on psycho-educational interventions in asthma , 74 adults with moderate to severe asthma were r and omly allocated to fill a symptoms diary for 1 month . Of these , 37 dropped-out of the trial and the remaining 47 ( 63 % ) completed a self-administered question naire about asthma monitoring . These two groups did not differ significantly regarding age , education , socio-economic status , and asthma severity . Approximately one-third was younger than 31 years and half was older than 40 years ; 84 % were female ; nearly 70 % had low socio-economic background ( class IV and V ) and 44 % had 5 or fewer years of formal education . FEV1 predicted % was below 80 % in 53 % , while 64 % were treated with high-dose inhaled steroids . During the previous year , 56 % had at least one exacerbation requiring oral steroids and one in five was admitted to a hospital because of their asthma . Only 28 % had ever self-monitored asthma before entering the study . However , none of the patients referred unwillingness to monitor their asthma in the future , and 56 % of them were strongly in favor to its use ; furthermore , one-third of patients were happy to monitor their symptoms daily , whereas another third preferred to do it less than once a week . Also , one in five considered it was easy to forget to register symptoms in the paper diary , and all patients considered it to help them better underst and their disease . The proportions of referred willingness to use mobile or web technologies to support self-management are described in Table 1 . There were no significant associations between willingness to use mobile or web technologies and patient ’s sex , age , education level , socio-economic status , tobacco usage , other chronic diseases , and duration and severity of asthma . Caution is needed in the generalization of these results as the patients who were studied were mostly middle-aged women with low education , and low socio-economic background , who had moderate to severe asthma followed at secondary care . Nevertheless , a large majority of patients seem willing and ready to use communication technologies such as mobile phones and the Web to help them manage their asthma . Are the doctors and the health administrators also ready to test the effectiveness of this AL LERGY 2 0 0 6 : 6 1 : 3 8 9 – 3 9 5 • COPYR IGHT a 2006 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REVIEW , BUT WILL BE REV IEWED BY THE ASSOCIATE EDITORS In this prospect i ve , multicenter , r and omized , controlled , double‐blind study , we investigated the impact of a mobile patient engagement application on health outcomes and quality of life in allergic rhinitis ( AR ) and asthma patients We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site r and omized control study . In this program , a nurse under physician supervision monitors the patient 's airway status at home and provides instructions to individuals via the telephone , helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan . Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and r and omly assigned to either the telemedicine or control group . After a six-month study period , an 83 % reduction in hospitalization was demonstrated in the telemedicine group versus the control group , with a P value of 0.01 . Improvement of peak expiratory flow and symptoms were also shown in the study group . We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring , compliance with prescribed daily prophylactic anti-inflammatory steroid medications , and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration This article reports on the development of a personalized , Web-based asthma-education program for parents whose 4- to 12-year-old children have moderate to severe asthma . Personalization includes computer-based tailored messages and a human coach to build asthma self-management skills . Computerized features include the Asthma Manager , My Calendar/Reminder , My Goals , and a tailored home page . These are integrated with monthly asthma-education phone calls from an asthma-nurse case manager . The authors discuss the development process and issues and describe the current r and omized evaluation study to test whether the year-long integrated intervention can improve adherence to a daily asthma controller medication , asthma control , and parent quality of life to reduce asthma-related healthcare utilization . Implication s for health education for chronic disease management are raised The adherence and disease-control outcomes associated with the use of an Internet-based store- and -forward video home telehealth system to manage asthma in children were studied . Pediatric patients with persistent asthma were provided with home computers and Internet access and monitored biweekly over the Internet . All patients were seen in the pediatric clinic at 0 , 2 , 6 , 12 , and 24 weeks . Half of the patients received asthma education in person and half via an interactive Web site . Adherence measures were assessed by therapeutic and diagnostic monitoring . Therapeutic monitoring included digital videos of patients using their controller medication inhaler . Diagnostic monitoring included an asthma symptom diary and a video of peak flow meter use . Videos were su bmi tted electronically twice a week by using in-home telemonitoring with store- and -forward technology . Feedback was provided electronically to each patient . Disease control was assessed by examining quality of life , utilization of services , rescue-therapy use , symptom control , satisfaction with home telemonitoring , and retention of asthma knowledge . Patients were r and omly assigned to an asthma education group ( Internet versus office ) , and the data were analyzed by comparing results for study days 0 - 90 and 91 - 180 . Ten children participated . A total of 321 videos of inhaler use and 309 videos of peak flow meter use were su bmi tted . Inhaler technique scores improved significantly in the second study period . Su bmi ssion of diagnostic monitoring videos and asthma diary entries decreased significantly . Peak flow values as a percentage of personal best values increased significantly . Overall , there was no change in quality of life reported by patients . However , the caregivers in the virtual-education group reported an increase in the patients ' quality -of-life survey scores . Emergency department visits and hospital admissions for asthma were avoided . Rescue therapy was infrequent . A high rate of satisfaction with home telemonitoring was reported . Internet-based , store- and -forward video assessment of children 's use of asthma medications and monitoring tools in their homes appeared effective and well accepted Objective . We previously conducted the School-Based Asthma Therapy trial to improve adherence to national asthma guidelines for urban children through directly observed administration of preventive asthma medications in school . The trial successfully improved outcomes among these children ; however , several factors limit its potential for dissemination . To enhance sustainability , we subsequently developed a new model of care using web-based guides for efficient communications and integration within school and community systems . This article describes the development of the School-Based Preventive Asthma Care Technology ( SB-PACT ) trial . Method . We developed the SB-PACT web-based system based on stakeholder feedback , and conducted a pilot r and omized trial with 100 children to establish its feasibility in facilitating preventive asthma care for high-risk children . The SB-PACT system represents a new model of care using web-based guides for asthma symptom screening , follow-up control assessment s , and electronic communications with providers . Result . We enrolled and successfully screened all children using the web-based system . Most providers used the electronic communication system without difficulty , and the majority of children in the intervention group received preventive medications through school as planned and dose adjustments as needed . Several challenges to implementation also were encountered . Conclusions . This program is design ed to promote sustainability of school-based asthma care , reduce program costs , and ultimately succeed in a real-world setting . With further refinements , it has the potential to be implemented nationally in schools Objectives . To evaluate the effects of an automated interactive voice response system ( IVR ) and Specialist Nurse Support to reduce health care utilization and improve health-related quality of life in children with asthma . Study Design . A r and omized controlled trial in 121 children with doctor-diagnosed asthma and an acute presentation with asthma in the previous 12 months aged between 3 and 16 years . Children were r and omized to one of three groups for a 6-month intervention receiving asthma education and management support from a Specialist Nurse by telephone or e-mail ( N = 41 ) , from IVR ( N = 39 ) , or receiving usual care ( control group ; N = 41 ) . Outcomes included health care utilization and use of oral steroid rescue . Health-related quality of life ( HRQOL ) data using the Pediatric Asthma Quality of Life Question naire and Pediatric Quality of Life Inventory were collected at baseline and at the end of the study . Results : There was no statistically significant benefit identified for either the IVR or the Nurse Support interventions for health care utilization , use of oral steroid rescue , or HRQOL compared with controls . Relative to controls , the incremental costs were −A$225.73 ( 95 % confidence interval [ CI ] : −A$840 , A$ 391 ) per child for the Nurse Support intervention and −A$451.45 ( −A$1075 , A$ 173 ) per child for IVR . The results were most sensitive to the frequency of admissions to hospital . Conclusion . This study suggested that both IVR and Nurse Support interventions may be cost-saving from a health system perspective , with IVR providing the greatest benefit and this pilot study provides a strong basis for developing larger trials with longer follow-up Background . Although regular follow-up is recommended for patients with asthma , the optimal frequency of such follow-up has not been defined . The purpose of this study was to evaluate the relationship of the interval between routine physician visits to asthma outcomes in patients with moderate persistent asthma . Methods . The study population was a volunteer sample of subjects aged 18 years or older with moderate persistent asthma requiring at least moderate doses of inhaled corticosteroids who were followed for at least 6 months by one of two allergists in a large staff model HMO . Subjects were r and omized to one of three groups : 1 ) monthly physician visits , 2 ) semi-annual physician visits , and 3 ) semiannual physician visits and monthly nurse phone calls . All subjects were advised to call their physician for questions or increased symptoms . The primary outcome variable was total asthma quality of life measured at baseline , 6 months and 12 months . Other outcome variables included specific asthma quality of life domains , spirometry , global asthma rating , satisfaction with treatment rating , and asthma re source and medication utilization during the one year of follow-up . Results . The final cohort included 29 patients per group . There were no significant differences between groups in baseline demographics , smoking history , spirometry , asthma quality of life , global rating , or satisfaction with treatment rating . As per the protocol , patients in the monthly physician visit group made significantly more routine visits during the study than other patients ( P<.0001 ) , but there were no other significant differences between groups in any of the other outcome variables at 6 months , 12 months , or during the year of the study . Conclusion . Patients with the characteristics of those in this study do not need routine follow-up visits more often than every 6 months . Further studies will be necessary to determine optimal follow-up intervals for patients with other degrees of asthma severity and for those followed in other setting BACKGROUND Asthma morbidity and mortality rates are high among young inner-city children . Lack of routine primary care provider visits , poor access to care , and poor patient-physician communication might be contributing factors . OBJECTIVE This study evaluated the effects of providing Breathmobile services only , a Facilitated Asthma Communication Intervention ( FACI ) only , or both Breathmobile plus FACI on asthma outcomes relative to st and ard care . METHODS Children with asthma ( n = 322 ; mean age , 4 years ; 53 % male ; 97 % African American ) were recruited from Head Start programs in Baltimore City and r and omized into 4 groups . Outcome measures included symptom-free days ( SFDs ) , urgent care use ( emergency department visits and hospitalizations ) , and medication use ( courses of oral steroids and proportion taking an asthma controller medication ) , as reported by caregivers at baseline , 6-month , and 12-month assessment s. Generalized estimating equations models were conducted to examine the differential treatment effects of the Breathmobile and FACI compared with st and ard care . RESULTS Children in the combined treatment group ( Breathmobile plus FACI ) had an increase of 1.7 ( 6.6 % ) SFDs that was not maintained at 12 months . In intent-to-treat analyses the FACI-only group had an increase in the number of emergency department visits at 6 months , which was not present at 12 months or in the post hoc as-treated analyses . No significant differences were found between the intervention groups compared with those receiving st and ard care on all other outcome measures . CONCLUSIONS Other than a slight improvement in SFDs at 6 months in the Breathmobile plus FACI group , the intervention components did not result in any significant improvements in asthma management or asthma morbidity Objectives . Asthmatic children and their parents constantly need to adjust their lifestyles due to asthma attacks . We evaluated the effectiveness of a self-management interactive support ( SMIS ) program for caregivers of asthmatic children . Methods . Children with persistent asthma were r and omized into two groups , one receiving SMIS and the other receiving usual care ( the control group ) . The SMIS program involved a three-month multifaceted behavioral intervention . Changes in the caregivers ’ knowledge and attitude regarding self-management , children ’s lung function , and number of emergency department visits and hospital admissions were examined at 12 months post-enrollment . Results . Sixty-five asthmatic children and caregivers ( 78 % follow-up ) completed the study . Primary caregivers in the SMIS group had significant improvements in knowledge and attitude regarding asthma compared to those in the control group ( p < .05 ) . Most importantly , knowledge about asthma medications and exacerbations significantly improved and attitudes toward medication adherence and dealing with asthma care became more positive in the SMIS group . The forced expiratory volume in one second was significantly improved in the SMIS group after 12 months ( p < .05 ) , and performance in the methacholine challenge test at the end of the study was significantly better in the SMIS group ( p < .05 ) . Participants in the SMIS group also had a lower rate of emergency room use ( p < .05 ) . Conclusion . The SMIS program for the self-management of asthma in children by their caregivers improved lung function and reduced the number of visits to the emergency departments . Interactive support interventions reinforce learning incentives and encourage self-care and maintenance of therapeutic regimens Context Patient self-management is an essential component of asthma care , and the Internet is a medium to potentially support patients in self-management . Contribution This r and omized trial compared Internet-based asthma self-management with usual care and found modest improvements in asthma control and lung function with the Internet intervention , but found no reduction in exacerbations and changes in asthma-related quality of life that were less than clinical ly significant at 12 months . Implication Although Internet-based self management can improve some asthma outcomes , the improvements were small and the program did not reduce the number of exacerbations . The Editors Asthma is a chronic disorder of the airways that is characterized by recurring respiratory symptoms , variable airflow obstruction , airway hyperresponsiveness , and underlying inflammation ( 1 , 2 ) . Recent clinical guidelines for the management of asthma distinguish 4 essential components of asthma care : assessment and monitoring , patient education , control of environmental and comorbid factors that affect asthma , and drug treatment . With appropriate medical care , well-informed and empowered patients can control their asthma and live full , active lives ( 1 , 2 ) . However , despite the availability of monitoring tools and effective therapy , asthma control is suboptimal in many patients worldwide , and long-term management falls far short of the goals set in the guidelines ( 3 ) . Self-monitoring , education , and specific medical care are important aspects in improving the lives of patients with asthma ( 1 , 2 ) . However , many patients with mild or moderate persistent asthma do not attend checkups regularly or visit their physician with symptoms of the disease ( 4 ) . In addition , in practice , both patients and their health care providers are reluctant to use written self-management plans ( 5 ) . Internet technology is increasingly seen as an appealing tool to support self-management for patients with chronic disease in remote and underserved population s ( 68 ) . However , to date , studies on Internet-based asthma self-management show only short-term improvements in asthma control , lung function , and quality of life ( 911 ) . Long-term studies on the effect of Internet-based self-management , including all its essential features , are not available . Therefore , we developed a guided self-management tool for adult patients with asthma that included Internet-based home monitoring and treatment advice ( action plan ) , online education , and remote Web communication with a specialized asthma nurse . The goal of our study was to assess the long-term clinical effectiveness of Internet-based self-management education compared with usual physician-provided care alone . Methods Design Overview We conducted a 12-month , multicenter , nonblinded , r and omized , controlled trial . We r and omly assigned patients to Internet-based self-management ( Internet group ) as an adjunct to usual care or to usual physician-provided care alone ( usual care group ) . The Internet-based self-management program included weekly asthma control monitoring and treatment advice , online and group education , and remote Web communications with a specialized asthma nurse . The intervention continued for 12 months after enrollment . The Medical Ethics Committee of the Leiden University Medical Center , Leiden , the Netherl and s , approved the study . Setting and Participants We recruited patients from 37 general practice s ( 69 general practitioners ) in the Leiden and The Hague area and the Outpatient Clinic of the Department of Pulmonology at the Leiden University Medical Center from September 2005 to September 2006 . Inclusion criteria were physician-diagnosed asthma coded according to the International Classification of Primary Care in the electronic medical record ( 12 ) , age 18 to 50 years , prescription of inhaled corticosteroids for at least 3 months in the previous year , no serious comorbid conditions that interfered with asthma treatment , access to the Internet at home , and mastery of the Dutch language . We excluded patients who were receiving maintenance oral glucocorticosteroid treatment . On the basis of diagnosis , age , prescribed asthma medication , and comorbid conditions , we sent eligible patients an invitation letter followed by 1 reminder letter after 2 to 4 weeks if they did not respond to the first . We continued this process until a total of 200 patients had entered the study ( September 2006 ) . All participants gave written consent . R and omization and Intervention In a 2-week baseline period before r and omization , we collected data on patient demographic characteristics , asthma-related quality of life , symptom control , lung function , and medication level . We provided basic education about core information on asthma , action of medications , and inhaler technique instructions to all patients . We trained all participants to measure FEV1 daily with a h and -held electronic spirometer ( PiKo-1 , Ferraris Respiratory , Hertford , United Kingdom ) and to report the highest value of 3 measurements in the morning before taking medication ( 2 , 13 ) . They were shown how to report these values on a personal page on a secure Web application by using a login password ( or how to report by mobile telephone text message ) . Patients were also asked to report their nighttime and daytime asthma symptom scores on this Internet page or by text message . We asked all participants to complete the Asthma Control Question naire on their personal Internet page each week ( 14 ) . We did not give any patients feedback about lung function or asthma control . After the 2-week baseline period , we r and omly assigned participants to either the Internet group or the usual care group . We stratified according to care provider ( primary vs. subspecialty care ) and asthma control at baseline ( 15 ) . We r and omly assigned patients to the 2 groups ( 1:1 ratio ) by using a computer-generated , permuted-block scheme . Allocation took place by computer after collection of the baseline data , ensuring concealment of allocation . The Internet-based self-management program consisted of the 4 principal components of asthma self-management and was accessed through the specially design ed Web site , which allowed monitoring through the Web site ( or text message on a mobile telephone ) , use of an Internet-based treatment plan , online education , and Web communications with a specialized asthma nurse ( 16 ) . Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Question naire on the Web site and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan ( Table 1 and Appendix Figures 1 , 2 , 3 , 4 , and 5 ) . Depending on the scores su bmi tted , patients received 4 types of self-treatment advice . When 4 consecutive Asthma Control Question naire scores were 0.5 or less , patients were advised to decrease treatment according to treatment plan . When 2 consecutive scores were greater than 0.5 but less than 1.0 , patients were advised to increase treatment according to treatment plan . When 1 score was 1.0 or more but less than 1.5 , patients were advised to immediately increase treatment according to treatment plan . Finally , when 1 score was 1.5 or more , patients were advised to immediately increase treatment and contact the asthma nurse . Table 1 . Treatment Plan Appendix Figure 1 . Algorithm based on consecutive ACQ scores to adjust medical treatment . * ACQ = Asthma Control Question naire . At entry of the algorithm , the evaluation period is bypassed . The evaluation period starts after treatment was stepped up . The optimal control period starts after 1 ACQ score 0.5 and ends after 1 ACQ score > 0.5 . Appendix Figure 2 . Screen shot of daily lung function and symptom monitoring . Appendix Figure 3 . Screen shot of feedback on daily lung function and symptom monitoring . Appendix Figure 4 . Screen shot of weekly Asthma Control Question naire monitoring . Appendix Figure 5 . Screen shot of feedback on Asthma Control Question naire , treatment advice according to personalized treatment plan , and results of past 6 months . We advised no medication changes during the 4 weeks after treatment was stepped up ( evaluation period ) . In addition to weekly assessment s , patients could optionally report daily symptoms and lung function and were able to contact our asthma nurse though the Web or by telephone . Thus , any acute deterioration warranting a visit to the general practitioner or hospital could be detected ( Appendix Figures 2 and 3 ) . We aim ed to empower patients to use the Internet-based self-management tool and to develop a patientprovider partnership in asthma care ( 2 ) . Self-management education consisted of both Web-based and face-to-face , group-based education . Web-based education included asthma information , news , frequently asked questions , and interactive communication with a respiratory nurse specialist . We scheduled 2 group-based education sessions , which lasted 45 to 60 minutes , for patients in the Internet-based self-management group within 6 weeks after entering the trial . Both sessions included exploration of a patient 's interests and previous knowledge ( negotiating an agenda and patient-centered education ) , personalized feedback , and empowerment of self-management ( self-efficacy and implementing a plan for change ) ( 2 , 17 ) . The first educational session also included pathophysiology of asthma , information on the Web-based action plan , and information and review of inhalation technique . The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance . Patients in the usual care group received asthma care according to the Dutch general practice guidelines on asthma management in adults , which recommend a medical review and treatment adjustment every 2 to 4 weeks in unstable asthma and medical review once or twice Background The rising prevalence of chronic conditions constitutes a major burden for patients and healthcare systems and is predicted to increase in the upcoming decades . Improving the self-management skills of patients is a strategy to steer against this burden . This could lead to better outcomes and lower healthcare costs . Health coaching is one method for enhancing the self-management of patients and can be delivered by phone . The effects of telephone-based health coaching are promising , but still inconclusive . Economic evaluations and studies examining the transferability of effects to different healthcare systems are still rare . Aim of this study is to evaluate telephone-based health coaching for chronically ill patients in Germany . Methods / Design The study is a prospect i ve r and omized controlled trial comparing the effects of telephone-based health coaching with usual care during a 4-year time period . Data are collected at baseline and after 12 , 24 and 36 months . Patients are selected based on one of the following chronic conditions : diabetes , coronary artery disease , asthma , hypertension , heart failure , COPD , chronic depression or schizophrenia . The health coaching intervention is carried out by trained nurses employed by a German statutory health insurance . The frequency and the topics of the health coaching are manual-based but tailored to the patients ’ needs and medical condition , following the concepts of motivational interviewing , shared decision-making and evidence -based-medicine . Approximately 12,000 insurants will be enrolled and r and omized into intervention and control groups . Primary outcome is the time until hospital readmission within two years after enrolling in the health coaching , assessed by routine data . Secondary outcomes are patient-reported outcomes like changes in quality of life , depression and anxiety and clinical values assessed with question naires . Additional secondary outcomes are further economic evaluations like health service use as well as costs and hospital readmission rates . The statistical analyses includes intention-to-treat and as-treated principles . The recruitment will be completed in September 2014 . Discussion This study will provide evidence regarding economic and clinical effects of telephone-delivered health coaching . Additionally , this study will show whether health coaching is an adequate option for the German healthcare system to address the growing burden of chronic diseases . Trial registration German Clinical Trials Register ( Deutsches Register Klinischer Studien ; DRKS ) DRKS00000584 OBJECTIVE To assess the feasibility , acceptability , and preliminary impact of a telepharmacy intervention in an underserved , rural asthma patient population . SUBJECTS AND METHODS Patients with asthma were r and omized to receive either st and ard care or telephone consultations from pharmacists regarding asthma self-management over a 3-month period . Qualitative interviews were conducted to identify participants ' attitudes/opinions regarding the intervention . Baseline and follow-up surveys assessed asthma control , patient activation , and medication utilization . RESULTS Ninety-eight adults were recruited ( 78 % accrual ) ; 83 completed the study ( 15 % dropout ) . Participants reported positive opinions and believed the intervention improved their asthma self-management . The intervention group had significantly higher patient activation compared with the control ( p<0.05 ) . There were no significant between-group differences regarding asthma control . However , within-group analyses of the intervention group showed an improvement in asthma control ( p<0.01 ) and medication adherence ( p<0.01 ) . No within-group differences were found for the control group . CONCLUSIONS This telepharmacy intervention is feasible and showed indicators of effectiveness , suggesting the design is well suited for a robust study to evaluate its impact in uncontrolled asthma patients . Pharmacists helping patients manage asthma through telecommunications may resolve access barriers and improve care BACKGROUND AND OBJECTIVE Poorly controlled asthma during pregnancy is hazardous for both mother and foetus . Better asthma control may be achieved if patients are involved in regular self-monitoring of symptoms and self-management according to a written asthma action plan . Telehealth applications to optimize asthma management and outcomes in pregnant women have not yet been evaluated . This study evaluated the efficacy of a telehealth programme supported by a h and held respiratory device in improving asthma control during pregnancy . METHODS Pregnant women with asthma ( n = 72 ) from two antenatal clinics in Melbourne , Australia , were r and omized to one of two groups : ( i ) intervention-involving a telehealth programme ( management of asthma with supportive telehealth of respiratory function in pregnancy ( MASTERY ( © ) ) ) supported by a h and held respiratory device and an And roid smart phone application ( Breathe-easy ( © ) ) and written asthma action plan or ( ii ) control-usual care . The primary outcome was change in asthma control at 3 and 6 months ( prenatal ) . Secondary outcomes included changes in quality of life and lung function , and perinatal/neonatal outcomes . RESULTS At baseline , participants ' mean ( ± st and ard deviation ) age was 31.4 ± 4.5 years and gestational age 16.7 ± 3.1 weeks . At 6 months , the MASTERY group had better asthma control ( P = 0.02 ) and asthma-related quality of life ( P = 0.002 ) compared with usual care . There were no significant differences between groups in lung function , unscheduled health-care visits , days off work/ study , oral corticosteroid use , or perinatal outcomes . Differences between groups were not significant at 3 months . CONCLUSION Telehealth interventions supporting self-management are feasible and could potentially improve asthma control and asthma-related quality of life during pregnancy BACKGROUND We examined the feasibility of self-directed Triple P ' Positive Parenting Programme ' for optimizing parents ' management of childhood asthma and behaviour . METHODS Eligible families were invited to access asthma-specific web-based Triple P as part of a preliminary r and omized controlled study . RESULTS Initial study information and introductory website pages received considerable interest but intervention uptake was poor with high rates of attrition . CONCLUSIONS Although parents of children with asthma show willingness to access web-based parenting support , further work is necessary to develop engaging websites and determine barriers to uptake , and adherence to online parenting interventions with this population The CYMPLA trial . Mobile phone-based str rct rred intervention to achieve asthma control in patients with rncontrolled persistent asthma : a pragmatic r and omised controlled OBJECTIVE To describe medication therapy management ( MTM ) services via videoconferencing . DESIGN A descriptive , cross-sectional analysis of an ongoing prospect i ve , r and omized-controlled study . SETTING A secured seven-pharmacy network connected by computers , webcams , telephones , and electronic medical records . PARTICIPANTS Patients 18 years of age or older ; taking four or more chronic medications ; and with diabetes , hypertension , hyperlipidemia , asthma/chronic obstructive pulmonary disease , multiple sclerosis , and /or Parkinson 's disease . INTERVENTIONS Chart review s and videoconferencing interviews to identify medication-related problems ( MRP ) and provide patient education and recommendations to providers . MAIN OUTCOME MEASURES Patient demographics , identified MRPs , interventions , and patient satisfaction . RESULTS During April to July 2010 , 43 patients were interviewed ( mean age 50.8 ± 11.5 years ) ; of these , 12 patients ( 27.9 % ) were older adults , mean age 69.5 ± 5.0 years . Prevalent health conditions were hypertension ( 31/43 , 72 % ) , hyperlipidemia ( 28/43 , 65 % ) , and diabetes ( 19/43 , 44 % ) . A mean number of 3.5 ± 2.3 MRP/patient was identified . Compared with charted numbers , patients significantly under-reported their health conditions ( selfreported mean number 4.0 ± 1.6 , compared with 6.9 ± 3.3 , P < 0.0001 ) and medications used ( self-reported mean number 7.7 ± 3.4 , charted number 9.4 ± 2.3 , P < 0.005 ) . Providers accepted a mean number of 2.2 ± 1.6 ( out of 2.8 ± 1.3 ) pharmacist-provided recommendations ( acceptance rate 78.6 % ) . All patients interviewed agreed or strongly agreed that the MTM interview with pharmacist and the information provided were helpful . CONCLUSION Webcam-enabled videoconferencing allows effective interactions between pharmacists and patients to identify MRP and improve access to MTM services . Provider acceptance of pharmacist-provided recommendations and patient satisfaction with videoconferencing MTM services are high |
11,133 | 30,290,663 | Conclusion : Our study confirmed that AC-IOLs can provide cataract patients with DCNVA and result in more high levels of spectacle independence than MF-IOLs . | Introduction : We performed a systematic review and meta- analysis to evaluate whether accommodative intraocular lenses ( AC-IOLs ) are superior for cataract patients compared with monofocal IOLs ( MF-IOLs ) . | PURPOSE To compare the visual performance of patients with unilateral cataract following implantation of monofocal , accommodating , refractive , and diffractive multifocal intraocular lenses ( IOL ) . DESIGN Prospect i ve nonr and omized clinical trial . METHODS Eighty-seven patients with unilateral cataract were enrolled in 4 groups for phacoemulsification and IOL implantation . Twenty-four patients had monofocal ( Alcon Acrysof ) ( group 1 ) , 21 patients had accommodating ( Human Optics 1CU ) ( group 2 ) , 22 patients had diffractive multifocal ( Tecnis ZM900 ) ( group 3 ) , and 20 patients had refractive multifocal ( AMO Rezoom ) ( group 4 ) IOL implantations . Ages of patients were between 40 and 70 . Parameters analyzed at the 18th postoperative month were subjective refractions , monocular and binocular distance , intermediate and near uncorrected visual acuities , monocular distance and near best-corrected visual acuities , monocular distance-corrected intermediate and near visual acuities , stereopsis , visual complaints , and spectacle dependency . RESULTS No significant difference was observed between distance and near best-corrected visual acuities of IOL groups , and between intermediate visual acuities of groups 2 , 3 , and 4 . Groups 3 and 4 had statistically better near vision than the other groups ( P < .05 ) . No significant difference was observed between near visual acuities of groups 3 and 4 . Number of patients with better stereoscopic function , spectacle independence , and complaints of halo in groups 3 and 4 was significantly higher than in other groups ( P < .05 ) . CONCLUSIONS Multifocal IOLs provide better stereopsis , higher spectacle independence rates , and satisfactory functional vision over a broad range of distances in presbyopic patients with unilateral cataract compared with the monofocal and accommodating IOLs 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 measure the axial movement of an accommodating intraocular lens ( IOL ) induced by ciliary muscle contraction after application of pilocarpine . DESIGN R and omized , controlled , patient- and examiner-masked trial with intrapatient comparison . PARTICIPANTS AND CONTROLS One hundred ten eyes of 55 patients with age-related bilateral cataract . METHODS This study was divided into 3 parts . In the first , the accommodating IOL ( 1CU ) was compared with a 3-piece open-loop acrylic IOL that served as the control . In the second , to assess the effect of capsule fibrosis on the potential accommodating performance of the accommodating IOL , extensive polishing of the anterior capsule with a slit cannula was compared with st and ard surgery . In the third , the effect of a posterior capsulorhexis was compared with that of st and ard surgery . Anterior chamber depth ( ACD ) was assessed with partial coherence interferometry , measured before and after topical application of pilocarpine 2 % , and near visual acuity ( VA ) was evaluated 3 months after surgery . MAIN OUTCOME MEASURE Pilocarpine-induced change in ACD . RESULTS The accommodating IOL showed a forward movement under pilocarpine with a median amplitude of movement of -314 microm ( 95 % confidence interval [ CI ] : -148 to -592 ) , compared with the backward movement of 63 microm ( 95 % CI : 161 to -41 ) for the open-loop control IOL ( P = 0.001 ) . Capsule polishing and a posterior capsulorhexis had no effect on IOL movement with the accommodating IOL . The median near VA with distance correction was 20/60 . CONCLUSION Pilocarpine induced a small but significant forward movement of the accommodating IOL . However , the amount of movement was calculated to result in a refractive change of < 0.5 diopters ( D ) in most patients , reaching 1 D or slightly more in only single cases , with a large variability of movement . Neither polishing of the capsule bag nor a posterior capsulorhexis could enhance the accommodative ability OBJECTIVE To compare the binocular near vision performance in patients implanted with the 1CU accommodating intraocular lens ( IOL ) with a multifocal and monofocal IOL . DESIGN Prospect i ve , r and omized , double-masked clinical trial . PARTICIPANTS Ninety patients presenting for cataract surgery to the Department of Ophthalmology , Hillingdon Hospital were r and omized to receive the 1CU accommodative IOL , a multifocal IOL , or a monofocal IOL ( control group ) . METHODS Patients underwent bilateral sequential phacoemulsification with implantation of 1 of the 3 IOL types and were assessed at 3 and 18 months after second-eye surgery . MAIN OUTCOME MEASURES Logarithm of the minimum angle of resolution distance and near visual acuities ( VAs ) ( unaided and distance corrected ) , contrast sensitivity , and accommodative amplitude ( near point and defocusing ) were measured at 3 and 18 months . Reading speed was assessed at 18 months , and glare symptoms and spectacle independence were compared using a st and ardized question naire . RESULTS Mean unaided and distance-corrected binocular near VAs were similar in the 1CU and multifocal and were significantly higher than the control group 's ( P<0.02 ) . There was no significant difference in reading speed between any of the groups , but critical print sizes were similar in the 1CU and multifocal groups and significantly better than the control group 's ( P = 0.02 ) . The accommodative range was highest in the multifocal group and lowest in the control group , and there was no significant difference between the 1CU and control groups for defocus or near point at 18 months . Of the 1CU group and control group , 71.4 % and 63.2 % , respectively , experienced no glare at 18 months , compared with only 25 % of the multifocal group ( P = 0.01 ) . Of the 1CU group and multifocal group , 19 % and 27.3 % , respectively , were completely spectacle independent at 18 months ; none of the control group was ( P = 0.05 ) . CONCLUSIONS The 1CU accommodating IOL provides improved near vision compared with a monofocal IOL . There is a discrepancy between the near function and accommodative amplitude measured in the 1CU . The multifocal provides excellent near acuity , but photopic phenomena remain a problem inherent in the lens design Aim : To assess the accommodative power of a new foldable monofocal intraocular lens . Method : A prospect i ve r and omised non-masked clinical interventional study . The study included 40 patients attending the hospital for cataract surgery and who were r and omly distributed into a study group receiving a new foldable monofocal intraocular lens with flexible haptics , and a control group receiving a st and ard foldable intraocular lens . Mean follow up period was 8.51 ( SD 1.34 ) months ( range 4–11 months ) St and ard cataract surgery consisted of clear cornea incision , capsulorrhexis , phacoemulsification , and intraocular lens implantation , with topical anaesthesia . The main outcome measures were preoperative and postoperative visual acuity for near and distance ; range of accommodation ; change in anterior chamber depth . Results : In the study group compared with the control group , range of accommodation was significantly ( p = 0.01 ) higher ( 1.01 ( SD 0.4 ) dioptres versus 0.50 ( 0.11 ) dioptres ) and change in anterior chamber depth was significantly more pronounced ( 0.82 ( 0.30 ) versus 0.40 ( 0.32 ) , p = 0.01 ) . Both groups did not vary significantly in best corrected vision ( 0.94 ( 0.12 ) versus 0.93 ( 0.18 ) ; p = 0.74 ) . Conclusion : During a mean follow up period of 8 months after implantation , the new foldable monofocal intraocular lens with flexible haptics showed an accommodative power of about 1 dioptre , which was significantly higher than the accommodative power of a conventional monofocal flexible intraocular lens . The difference in the accommodative power between the two intraocular lenses was paralleled by a difference in the change of the anterior chamber depth PURPOSE To evaluate the age-related change in contrast sensitivity seen in a middle-aged to elderly Japanese population . METHODS Contrast sensitivity and visual acuity were measured in subjects aged 40 to 79 years r and omly recruited from a community in Aichi prefecture near Nagoya , Japan . Contrast sensitivity tests were performed using the Vistech contrast sensitivity test chart ( VCTS 6500 ) . The results were statistically analyzed relative to age . RESULTS A statistically significant decrease in contrast sensitivity was seen with advancing age at each spatial frequency ( Cochran-Mantel-Haenszel : P<.001 ) . This trend was detected even when the subjects were limited to only those having a corrected visual acuity of 1.0 or better ( Cochran-Mantel-Haenszel : P<.001 ) . Overall , 9.4 % of the eyes with good visual acuity had poor contrast sensitivity at a high spatial frequency , while in the 70 - 79-year-old group , the percentage with poor contrast sensitivity reached 21.1 % . CONCLUSIONS The age-related decrease in contrast sensitivity was confirmed at all frequencies in our population , even when adjusted for visual acuity . Our results suggest that contrast sensitivity tests , especially at high frequencies , assess aspects of visual function that can not be determined in the elderly population from visual acuity tests alone PURPOSE To evaluate selected functional and physical properties of 2 models of accommodative intraocular lenses ( IOLs ) compared with those of a st and ard monofocal IOL . DESIGN Prospect i ve r and omized comparative trial . PARTICIPANTS Subjects were divided into 3 groups . In group 1 , 30 eyes ( 19 subjects ) received 1CU IOL implantation ; in group 2 , 29 eyes ( 19 subjects ) received AT-45 IOL implantation ; and in group 3 , 21 eyes ( 21 subjects ) were implanted with a monofocal IOL as a control . INTERVENTION Cataract surgery with implantation of the 1CU and AT-45 accommodative IOL models in the study groups , and the ACR6D monofocal IOL in the control group . MAIN OUTCOME MEASURES Far and near distance visual parameters were assessed at 1 , 6 , and 12 months after surgery in the accommodative IOL groups , and at 1 and 12 months in the control group . Anterior segment anatomy was investigated by ultrasound biomicroscopy , with and without visual accommodative stimulation . RESULTS The accommodative IOL groups significantly differed from the controls in terms of lower near-distance refractive addition ( NDRA ) and better distance-corrected near visual acuity ( DCNVA ) , with P<0.001 at 1 year . The anterior IOL displacement during accommodation ( DeltaACD ) was significantly larger in the study groups , and this correlated with DCNVA . Until 6 months , the DeltaACD correlated with the solicited sclerociliary process rotation only in the study groups . CONCLUSION This 12-month study demonstrated that the accommodating IOLs achieved better clinical results than the monofocal IOL in terms of DCNVA and NDRA . These results support the hypothesis that accommodative IOLs proportionally react to ciliary body rotation , although this relationship became less evident at 12 months Purpose To compare visual acuity , intraocular lens ( IOL ) movement , and depth of focus with the Crystalens HD single‐optic accommodating IOL and the Tecnis ZCB00 aspheric monofocal IOL . Setting St. Thomas ’ Hospital , London , United Kingdom . Design Prospect i ve r and omized controlled trial . Methods Patients with bilateral symptomatic cataract had bilateral sequential cataract surgery within 6 weeks with r and omized implantation of the accommodating or monofocal IOL in both eyes . Exclusion criteria included other ocular conditions and corneal astigmatism greater than 2.00 diopters . The primary outcome was uniocular distance‐corrected near visual acuity ( DCNVA ) . Secondary measures were IOL movement , depth of focus , intermediate and distance vision , objective refraction , and pupil size at distance and near fixation . Results from 3 months postoperatively are presented . Results Three months postoperatively , 64 patients ( 32 in each group ) were available for study . The distance vision was not statistically significantly different between the accommodating IOL and monofocal IOL ( mean 0.05 logMAR versus 0.06 logMAR ) . The mean DCNVA ( 0.48 logMAR ± 0.15 [ SD ] versus 0.61 ± 0.13 logMAR ) and intermediate visual acuity ( 0.08 ± 0.1 logMAR versus 0.20 ± 0.09 logMAR ) were significantly better with the accommodating IOL ( P<.001 ) . Neither IOL had clinical ly significant movement , and near vision did not directly correlate with movement of the accommodating IOL . The accommodating IOL provided greater depth of focus . Conclusions Near and intermediate acuities were better with the accommodating IOL . This effect was not directly linked to IOL movement but was at least partly due to depth of focus . Financial Disclosure Dr. Spalton is a consultant to Bausch & Lomb . No author has a financial or proprietary interest in any material or method mentioned Purpose : To compare the near functional capacities of patients with an accommodating intraocular lens ( IOL ) with those of patients with a conventional monofocal IOL . Setting : Department of Ophthalmology , University of Chieti , Chieti , Italy . Methods : This prospect i ve double‐blind case‐control study comprised 42 eyes that had phacoemulsification and implantation of 1 of 2 types of IOLs : HumanOptics accommodating 1CU ® ( study group ) and Eurocrystal IFP 3 G 6.00 ( control group ) . The main outcome measures were subjective refraction , uncorrected distance acuity , best corrected distance acuity , distance corrected near acuity at 40 cm , best corrected near acuity at 40 cm , and subjective amplitude of accommodation . Patients were examined 7 , 30 , 90 , and 180 days after surgery . Results : Postoperatively , both groups had excellent uncorrected distance acuity , best corrected distance acuity , and best corrected near acuity . In the study group , the mean distance corrected near acuity ( Jaeger ) was 5.43 ± 0.98 ( SD ) ( range 4 to 7 ) at 7 days , 2.33 ± 0.48 ( range 2 to 3 ) at 1 and 3 months , and 3.66 ± 2.12 ( range 2 to 7 ) at 6 months . In the control group , the mean distance corrected near acuity was 7.43 ± 0.50 ( range 7 to 8) during the entire follow‐up . The differences between the groups was statistically significant ( P<.001 ) . The mean amplitude of accommodation was 0.00 diopter ( D ) in the control group and 1.14 ± 0.44 D ( range 0.75 to 2.00 D ) in the study group at 7 days , 2.36 ± 0.28 D ( range 2.00 to 2.75 D ) at 30 and 90 days , and 1.90 ± 0.77 D ( range 0.75 to 2.75 D ) at 6 months . Conclusions : The 1CU accommodating IOL provided better useful spectacle‐free near visual acuity than the conventional monofocal IOL . However , the accommodating mechanism can play a role in capsule fibrosis OBJECTIVE To evaluate the clinical outcomes in cataract patients after implantation of an accommodating intraocular lens , design ed to move forward and backward along the visual axis . DESIGN Prospect i ve , noncomparative case series . PARTICIPANTS Sixty-two patients scheduled for small-incision , extracapsular cataract extraction by phacoemulsification . METHODS Twenty-eight eyes of 14 patients in the feasibility phase of the study and 48 eyes of 48 patients in the next phase of study underwent cataract extraction and implantation of the AT-45 accommodating intraocular lens . Prospect i ve follow-up was analyzed at 1 month after surgery and compared with baseline characteristics 1 month and 3 to 6 months after surgery . MAIN OUTCOME MEASURES Postoperative distance ( uncorrected and best corrected ) , near ( uncorrected , through the distance correction , best-corrected , i.e. , with add ) , and intermediate ( through the distance correction ) visual acuity . RESULTS All patients with monocular pseudophakia had best-corrected distance visual acuity of 20/40 or better . Patients with bilateral pseudophakia had best-corrected visual acuity of 20/25 or better when tested binocularly . The results from 28 eyes of 14 patients participating in the feasibility study were combined with those from 48 eyes of 48 patients included in the next phase of the AT-45 study . Uncorrected distance visual acuity was 20/40 or better in most patients ( 90 % , or 56 of 62 eyes implanted and available for follow-up ) . Ninety-seven percent of patients ( 60/62 ) had uncorrected near visual acuity of 20/30 or better . Forty-eight eyes had intermediate visual acuity measured at 28 inches without ' add ' , and 44 of them ( 92 % ) achieved 20/30 or better . No complications or adverse events were reported . CONCLUSIONS The AT-45 accommodating intraocular lens , design ed to allow movement along the visual axis of the eye by using the natural physiology of the intact ciliary muscle after cataract removal , provides patients with excellent uncorrected distance , intermediate , and near visual acuity and should be considered as a modality to allow the majority of pseudophakic patients to see at all distances without glasses PURPOSE To compare visual acuity , accommodation , and contrast sensitivity of the AkkoLens Lumina accommodative intraocular lens ( AkkoLens Clinical b.v . , Breda , The Netherl and s ) with a st and ard monofocal intraocular lens ( IOL ) . DESIGN R and omized clinical trial . METHODS The study enrolled 86 eyes with cataract that all required cataract surgery and IOL implantation . The study group included 61 eyes that were implanted with the Lumina . The control group included 25 eyes that were implanted with an Acrysof SA60AT ( Alcon , Fort Worth , TX , USA ) monofocal IOL . The distance and near visual acuities , contrast sensitivity , and accommodation were measured over a 1-year follow-up period . Accommodation was measured subjectively , using defocus curves , and objective ly , with an open-field autorefractor . RESULTS Uncorrected ( UDVA ) and corrected ( CDVA ) distance visual acuities did not differ significantly between the groups ( P ≥ .21 ) over the 12 months . However , the uncorrected near visual acuity ( UNVA ) was 0.07 ± 0.08 logRAD for the Lumina group and 0.37 ± 0.19 logRAD for the control group ( P < .01 ) and the corrected distance near visual acuity ( CDNVA ) was 0.11 ± 0.12 LogRAD for the Lumina group and 0.41 ± 0.15 LogRAD for the control group ( P < .01 ) . Defocus curves showed a statistically significant difference between groups for defocus ranging from -4.50 to -0.50 diopters ( D ) ( P < .01 ) with significantly higher visual acuities for the Lumina group . Subjective accommodation , as determined from defocus curves , was 3.05 ± 1.06 , 3.87 ± 1.27 , and 5.59 ± 1.02 D for the Lumina group and 1.46 ± 0.54 , 2.00 ± 0.52 , and 3.67 ± 0.75 D for the control group at visual acuities of 0.10 , 0.20 , and 0.4 logMAR for both groups , respectively . The objective accommodation , measured by an open-field autorefractor , was 0.63 ± 0.41 , 0.69 ± 0.45 , 0.91 ± 0.51 , and 1.27 ± 0.76 D for the Lumina group and 0.10 ± 0.15 , 0.12 ± 0.15 , -0.06 ± 0.09 and 0.07 ± 0.10 D for the control group at accommodation stimuli of 2.0 , 2.5 , 3.0 , and 4.0 D , respectively . Contrast sensitivity was the same for both groups ( P ≥ .26 ) . CONCLUSIONS The Lumina accommodative IOL effectively restores the visual function , accommodation , and contrast sensitivity after cataract surgery with no influence on the postoperative contrast sensitivity PURPOSE To examine the near visual clinical performance of an accommodative intraocular lens ( IOL ) when compared with a st and ard monofocal IOL in a fellow eye comparison . DESIGN Prospect i ve , r and omized fellow eye comparison . METHODS Thirty patients ( 60 eyes ) with bilateral cataracts but otherwise normal eyes were recruited from a single university hospital cataract waiting list . Patients were r and omized to receive either the 1CU accommodative IOL in their first eye or the Acrysof MA30 monofocal IOL . The alternative lens was then implanted in the second eye 4 to 6 weeks later . At all follow-up visits , a full assessment was made of distance , near and reading visual performance , and accommodative amplitude . RESULTS Data are available for all patients at 6 months and 20 patients at 1 year . At 6 months , no difference was found in distance-corrected visual acuity between the two IOLs . Of the 1CU eyes , nine patients ( 30 % ) could read J6 or better at a reading speed of 80 words/min or better . In these nine patients , the mean difference in the amplitude of accommodation between the two eyes was 0.71 diopters . CONCLUSIONS No measurable variable distinguished eyes that developed functional reading vision from those that did not . The accommodative IOL appears to produce improved near vision in some eyes , but it does not work in all eyes , and in eyes where there is apparent accommodation , there is a discrepancy between subjective reading performance and the modest measured increase of accommodative amplitude ABSTRACT Objective : The primary objective of this research was to compare cataract patient-reported outcomes of subjects bilaterally implanted with apodized diffractive intraocular lenses ( AD-IOL ) to subjects bilaterally implanted with conventional monofocal intraocular lenses ( CM-IOL ) . A secondary objective was to establish the relationship between uncorrected visual acuity and patient-reported outcomes . Methods : This was a prospect i ve non-r and omized , open-label clinical trial consisting of 339 patients bilaterally implanted with the AD‐IOL and 156 bilaterally implanted with the CM‐IOL . The outcomes of both groups were assessed 6 months postoperatively after second eye implantation . Assessed endpoints included patient-reported outcomes and visual acuity . Limitations of this study include the lack of r and om assignment to treatment groups and lack of masking of both the physicians and patients . Results : AD‐IOL patients demonstrated significantly better uncorrected near visual acuity ( UCNVA ) compared to CM‐IOL patients ( 0.02 versus 0.41 log MAR [ logarithm of the minimum angle of resolution ] , respectively ; p < 0.0001 ) . UCNVA was significantly correlated with nine patient-reported outcomes in the AD‐IOL group and two patient-reported outcomes in the CM‐IOL group . Significantly more AD‐IOL patients reported spectacle independence compared to CM patients ( 80 % versus 8 % respectively ; p < 0.0001 ) . AD‐IOL patients reported their vision quality as better than CM‐IOL patients ( p < 0.0001 ) . AD‐IOL patients were more satisfied with their daytime ( p < 0.0001 ) , nighttime ( p = 0.0013 ) , and overall ( p < 0.0001 ) vision than CM‐IOL patients . AD‐IOL patients reported less trouble with their daytime ( p < 0.0001 ) and nighttime ( p = 0.0238 ) vision compared to CM‐IOL patients . Furthermore , AD‐IOL patients reported less distance vision limitation ( p = 0.0282 ) , less near vision limitation ( p < 0.0001 ) , and less social limitation ( p < 0.0001 ) than CM‐IOL patients . Conclusions : The patient reported near vision benefits of the AD‐IOL coupled with its high rate of spectacle independence significantly improved cataract patients ’ health-related quality -of-life , compared to a CM‐IOL PURPOSE To assess the efficacy of the Tetraflex ( Lenstec Inc ) intraocular lens ( IOL ) to provide enhanced near reading ability and spectacle independence relative to a monofocal control IOL in bilaterally implanted eyes tested binocularly . METHODS A prospect i ve , age-matched , non-r and omized US Food and Drug Administration clinical trial of 255 Tetraflex and 101 monofocal IOL control patients was performed . To date , 239 Tetraflex and 96 control patients were examined at 12 months postoperatively . RESULTS At 12 months postoperative , the Tetraflex patients read better than the controls at print sizes of 20/80 ( P=.04 ) , 20/63 ( P=.01 ) , 20/50 ( P<.001 ) , 20/40 ( P=.001 ) , 20/32 ( P<.001 ) , and 20/25 ( P=.001 ) . The proportion of patients reading at a speed of ≥80 words per minute was significantly higher with the Tetraflex IOL ( P=.003 ) . Ninety-six percent of Tetraflex patients reported never wearing glasses for distance compared with 80 % of control patients ( P<.001 ) . Seventy-five percent of the Tetraflex patients reported near spectacle wear either never or only occasionally for small print and /or dim light ( 21 % never ) compared with 46 % of control patients ( P<.001 ) ( 9 % never ) . Near add power requirement for corrected near visual acuity was less in the Tetraflex group ( P<.001 ) ; 28 % of Tetraflex patients required ≤1.25 diopters of near add , compared to only 7 % of control patients . Spectacle independence , as measured by the proportion of patients with uncorrected distance visual acuity of 20/25 or better and various degrees of uncorrected near visual acuity , was also significantly better ( P<.001 ) as was distance-corrected near visual acuity ( P<.001 ) . CONCLUSIONS The results support the efficacy of the Tetraflex IOL to provide enhanced near reading ability and spectacle independence relative to a monofocal IOL control PURPOSE To assess the degree of pseudoaccommodation amplitude correlated with shifts along the anteroposterior axis of the BioComFold foldable intraocular lens ( IOL ) . SETTING Department of Ophthalmology , Hôtel-Dieu Hospital , Paris , France . METHODS This prospect i ve study comprised 30 eyes of 30 patients operated on consecutively for cataract by phacoemulsification and in-the-bag implantation of a BioComFold ( 15 patients ) or a foldable control ( 15 patients ) IOL . The BioComFold IOL has a peripheral bulging ring that pushes the optic forward during the effort to accommo date , creating a zoom effect . Pseudoaccommodation amplitude was evaluated using the blurring of controlled vision by adding spheres , with the best correction for distance vision in place . Pupil diameter was measured with a Goldmann campimeter under constant illumination . Anterior chamber depth was determined by A-scan ( Paxial , Biophysic Medical ) 30 minutes after cyclopentolate 1 % was instilled and again 30 minutes after pilocarpine 2 % was instilled . RESULTS The difference in pseudoaccommodation amplitude and pupil diameter between the 2 groups was not statistically significant ( P = .6737 and P = .4014 , respectively ) . The IOL 's forward shifts from maximal ciliary relaxation to maximal ciliary contraction were significantly greater in the BioComFold group ( P = .0215 ) . CONCLUSION The design of the BioComFold IOL allowed greater forward optic shifts along the anteroposterior axis during the effort to accommo date . Nevertheless , this shift was not correlated with a significantly greater pseudoaccommodation amplitude A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis PURPOSE : To objective ly measure the shift and refractive change of the 1CU accommodating intraocular lens ( IOL ) ( HumanOptics ) and compare them to that of a monofocal AcrySof MA30 IOL ( Alcon Laboratories ) in the fellow eye . SETTING : Ophthalmology Department , St. Thomas ' Hospital , London , United Kingdom . METHODS : Thirty patients who had bilateral cataract surgery 18 to 24 months previously with a 1CU IOL prospect ively r and omly allocated to 1 eye and an AcrySof MA30 monofocal IOL to the other eye were examined . Distance correction , near vision , reading fluency , near point , and defocus to minus spheres were measured . Intraocular lens shift to an accommodative stimulus following instillation of pilocarpine 4 % was measured with the ACMaster . Refractive change between distance and near was measured with the Tracey wavefront analyzer . RESULTS : Of the original 30 patients recruited , complete measurements could only be obtained for 20 . There was no significant difference in near visual function with either IOL . A small anterior movement of the 1CU was seen with accommodation 0.010 mm ± 0.028 ( SD ) . After pilocarpine 4 % instillation , a forward movement of 0.220 ± 0.169 mm was seen with the 1CU compared to a backward movement of 0.028 ± 0.095 with the MA30 . There was no significant correlation between distance corrected near visual acuity and IOL movement . No change in spherical equivalent between distance and near was seen on wavefront analysis of either IOL . CONCLUSIONS : Small forward movement of the 1CU IOL was seen with accommodation and increased following pilocarpine , compared to the posterior movement of the MA30 IOL . The amount of the IOL shift was not sufficient to provide useful near vision , but the difference suggests that the engineering concept behind the 1CU IOL is valid Background : Owing to the improvement of modern intraocular lenses ( IOLs ) in terms of design and material , posterior capsule opacification ( PCO ) usually takes 2–3 years to develop . Thus , long term clinical evaluation of new implants is important . Methods : As part of a prospect i ve , non-r and omised FDA trial , the Rayner Centerflex , a foldable hydrophilic acrylic , single piece IOL was implanted in one eye of 83 patients ( mean age 73.5 ( SD 7.0 ) years ) . Over 3 years postoperatively , a st and ardised FDA protocol concerning IOL safety and efficacy was followed including evaluation of spherical equivalent ( SE ) , best corrected distance visual acuity ( BCDVA ) , endothelial cell count ( ECC ) , flare meter values , PCO development , and anterior capsule shrinkage . Results : Postoperatively , mean SE was stable ranging between −0.3D and 0.17D . After 1–2 months , all patients achieved a BCDVA of 20/40 or better . At 3–6 months postoperatively , mean ECC decreased from 2612 ( SD 346 ) cells/mm2 to 2380 ( 316 ) cells/mm2 . Mean PCO score for the entire optic increased from 0.20 ( 0.20 ) months ( 3–6 months postoperatively ) to 0.87 ( 0.57 ) result ing in a Nd : YAG rate of 29.41 % after 3 years . No anterior capsule shrinkage was found . Conclusion : The Centerflex showed excellent functional results , low values for endothelial cell loss and inflammatory signs , and no anterior capsule shrinkage . PCO formation was higher compared to other IOLs , which could be explained by the incomplete sharp edge at the optic-haptic junctions representing an “ Achilles ’ heel ” for cell ingrowth OBJECTIVE To assess the prevalence and causes of visual impairment and blindness in adults living in an urban area of southern China . METHODS R and om cluster sampling was used to identify the adults 50 years and older living in the Liwan district of Guangzhou , China . Presenting visual acuity ( PVA ) with habitual correction and best-corrected visual acuity ( BCVA ) based on autorefraction and subjective refraction were measured using the Early Treatment Diabetic Retinopathy Study visual chart . Blindness and low vision were defined according to World Health Organization criteria . Eyes with visual impairment were assigned 1 principal cause for the impairment . RESULTS Visual acuity measurements were available for 1399 adults 50 years and older ( 75.3 % participation rate ) . The prevalence of blindness and low vision based on the PVA was 0.6 % ( 95 % confidence interval , 0.2%-1.0 % ) and 10.1 % ( 95 % confidence interval , 8.5%-11.7 % ) , respectively . These rates were reduced to 0.5 % and 3.1 % when the BCVA was considered . Based on the PVA , the principal causes for blindness were cataract ( 39.6 % ) , glaucoma ( 11.0 % ) , and myopic maculopathy ( 6.6 % ) . The majority of low vision cases were attributable to cataract ( 45.3 % ) and uncorrected refractive error ( 43.9 % ) . CONCLUSION The majority of eye diseases leading to visual impairment are potentially treatable in this population |
11,134 | 30,312,656 | For quality appraisal , studies supported intensive training , piloting quality assessment tools , providing decision rules for poorly reported studies , contacting authors , and using structured tools if different study design s are included . | null | null |
11,135 | 20,166,099 | There were no documentations of death from any cause , morbidity , ( health-related ) quality of life and costs .
AUTHORS ' CONCLUSIONS There is insufficient evidence to recommend momordica charantia for type 2 diabetes mellitus . | BACKGROUND Momordica charantia is not only a nutritious vegetable , but is also used in traditional medical practice s to treat type 2 diabetes mellitus .
Experimental studies with animals and humans suggested that the vegetable has a possible role in glycaemic control .
OBJECTIVES To assess the effects of mormodica charantia for type 2 diabetes mellitus . | The effect of karela ( Momordica charantia ) , a fruit indigenous to South America and Asia , on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats . A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats . Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance . Improvement in glucose tolerance was not associated with an increase in serum insulin responses . These results show that karela improves glucose tolerance in diabetes . Doctors supervising Asian diabetics should be aware of the fruit 's hypoglycaemic properties Momordica charantia ( MC ) fruit was subjected to phytochemical and pharmacological interaction studies with oral hypoglycemis in NIDDM patients . Phytochemical , chromatographical analysis and extraction of methanolic MC fruit soft ( semi-solid form ) in CCl4 + C6H6 solvent system yielded 15 diverse chemical constituents -- alkaloids , glycosides , aglycone , tannin , sterol , phenol and protein . The CCl4 + C6H6 MC soft extract was used orally in a dose of 200 mg twice daily ( BD ) for pharmacological interactions with two diversely acting oral hypoglycemic agents--1 ) metformin BD and 2 ) glibenclamide BD in 15 patients of either sex ( 52 - 65 years of age ) of NIDDM . It was observed that with CCl4 + C6H6 MC soft extract plus half doses of metformin or glibenclamide or both in combination caused hypoglycemia greater than that caused by full doses used in the study with 7 days treatment . Conclusively the extract acts in synergism with oral hypoglycemics and potentiates their hypoglycemia in NIDDM Effect of Momordica charantia , a bitter vegetable popularly known as Karolla , on fasting and post pr and ial ( 2 hours after 75 gm oral glucose intake ) serum glucose levels were studied in 100 cases of moderate non-insulin dependent diabetic subjects . Drinking of the aqueous homogenized suspension of the vegetable pulp led to significant reduction ( p < 0.001 ) of both fasting and post-pr and ial serum glucose levels . This hypoglycaemic action was observed in 86 ( 86 % ) cases . Five cases ( 5 % ) showed lowering of fasting serum glucose only |
11,136 | 27,981,382 | Conclusion Magnetic sphincter augmentation appears to be an effective treatment for GERD with short-term outcomes comparable to the more technically challenging and time-consuming Nissen fundoplication . | Background The LINX ® magnetic sphincter augmentation system ( MSA ) is a surgical technique with short-term evidence demonstrating efficacy in the treatment of medically refractory or chronic gastroesophageal reflux disease ( GERD ) .
Currently , the Nissen fundoplication is the gold-st and ard surgical treatment for GERD .
We are the first to systematic ally review the literature and perform a meta- analysis comparing MSA to the Nissen fundoplication . | BACKGROUND This study was undertaken to evaluate our clinical experience during a 6-year period with an implantable device that augments the lower esophageal sphincter for gastroesophageal reflux disease ( GERD ) . The device uses magnetic sphincter augmentation ( MSA ) to strengthen the antireflux barrier . STUDY DESIGN In a single-center , prospect i ve case series , 100 consecutive patients underwent laparoscopic MSA for GERD between March 2007 and February 2012 . Clinical outcomes for each patient were tracked post implantation and compared with presurgical data for esophageal pH measurements , symptom scores , and proton pump inhibitor ( PPI ) use . RESULTS Median implant duration was 3 years ( range 378 days to 6 years ) . Median total acid exposure time was reduced from 8.0 % before implant to 3.2 % post implant ( p < 0.001 ) . The median GERD Health Related Quality of Life score at baseline was 16 on PPIs and 24 off PPIs and improved to a score of 2 ( p < 0.001 ) . Freedom from daily dependence on PPIs was achieved in 85 % of patients . There have been no long-term complications , such as device migrations or erosions . Three patients had the device laparoscopically removed for persistent GERD , odynophagia , or dysphagia , with subsequent resolution of symptoms . CONCLUSIONS Magnetic sphincter augmentation for GERD in clinical practice provides safe and long-term reduction of esophageal acid exposure , substantial symptom improvement , and elimination of daily PPI use . For c and i date s of antireflux surgery who have been carefully evaluated before surgery to confirm indication for MSA , MSA has become a st and ard treatment at our institution because control of reflux symptoms and pH normalization can be achieved with minimal side effects and preservation of gastric anatomy Background The techniques available for antireflux surgery have exp and ed with the introduction of the magnetic sphincter augmentation device ( MSAD ) for gastroesophageal reflux disease ( GERD ) . Methods A prospect i ve , multicenter registry evaluated MSAD and laparoscopic fundoplication ( LF ) in clinical practice ( Clinical Trials.gov identifier : NCT01624506 ) . Data collection included baseline characteristics , reflux symptoms , proton-pump inhibitor ( PPI ) use , side effects , and complications . Post-surgical evaluations were collected at one year . Results At report , 249 patients ( 202 MSAD patients and 47 LF patients ) had completed one-year follow-up . The LF group was older and had a greater frequency of large hiatal hernias and Barrett ’s esophagus than the MSAD group ( P < 0.001 ) . The median GERD-health related quality of life score improved from 20.0 to 3.0 after MSAD and 23.0 to 3.5 after LF . Moderate or severe regurgitation improved from 58.2 to 3.1 % after MSAD and 60.0 to 13.0 % after LF ( P = 0.014 ) . Discontinuation of PPIs was achieved by 81.8 % of patients after MSAD and 63.0 % after LF ( P = 0.009 ) . Excessive gas and abdominal bloating were reported by 10.0 % of patients after MSAD and 31.9 % following LF ( P ≤ 0.001 ) . Following MSAD , 91.3 % of patients were able to vomit if needed , compared with 44.4 % of those undergoing LF ( P < 0.001 ) . Reoperation rate was 4.0 % following MSAD and 6.4 % following LF . Conclusion Antireflux surgery should be individualized to the characteristics of each patient , taking into consideration anatomy and propensity and tolerance of side effects . Both MSAD and LF showed significant improvements in reflux control , with similar safety and reoperation rates . In the treatment continuum of antireflux surgery , MSAD should be considered as a first-line surgical option in appropriately selected patients without Barrett ’s esophagus or a large hiatal hernia in order to avoid unnecessary dissection and preserve the patient ’s native gastric anatomy . MSAD is an important treatment option and will exp and the surgeon ’s role in treating GERD BACKGROUND & AIMS It is important to evaluate the long-term effects of therapies for gastroesophageal reflux disease ( GERD ) . In a 12-year study , we compared the effects of therapy with omeprazole with those of antireflux surgery . METHODS This open , parallel group study included 310 patients with esophagitis enrolled from outpatient clinics in Nordic countries . Of the 155 patients r and omly assigned to each arm of the study , 154 received omeprazole ( 1 withdrew before therapy began ) , and 144 received surgery ( 11 withdrew before surgery ) . In patients who remained in remission after treatment , post-fundoplication complaints , other symptoms , and safety variables were assessed . RESULTS Of the patients enrolled in the study , 71 who were given omeprazole ( 46 % ) and 53 treated with surgery ( 37 % ) were followed for a 12-year follow-up period . At this time point , 53 % of patients who underwent surgery remained in continuous remission , compared with 45 % of patients given omeprazole with a dose adjustment ( P = .022 ) and 40 % without dose adjustment ( P = .002 ) . In addition , 38 % of surgical patients required a change in therapeutic strategy ( eg , to medical therapy or another operation ) , compared with 15 % of those on omeprazole . Heartburn and regurgitation were significantly more common in patients given omeprazole , whereas dysphagia , rectal flatulence , and the inability to belch or vomit were significantly more common in surgical patients . The therapies were otherwise well-tolerated . CONCLUSIONS As long-term therapeutic strategies for chronic GERD , surgery and omeprazole are effective and well-tolerated . Antireflux surgery is superior to omeprazole in controlling overall disease manifestations , but post-fundoplication complaints continue after surgery BACKGROUND & AIMS Based on results from year 2 of a 5-year trial , in 2012 the US Food and Drug Administration approved the use of a magnetic device to augment lower esophageal sphincter function in patients with gastroesophageal reflux disease ( GERD ) . We report the final results of 5 years of follow-up evaluation of patients who received this device . METHODS We performed a prospect i ve study of the safety and efficacy of a magnetic device in 100 adults with GERD for 6 months or more , who were partially responsive to daily proton pump inhibitors ( PPIs ) and had evidence of pathologic esophageal acid exposure , at 14 centers in the United States and The Netherl and s. The magnetic device was placed using st and ard laparoscopic tools and techniques . Eighty-five subjects were followed up for 5 years to evaluate quality of life , reflux control , use of PPIs , and side effects . The GERD-health-related quality of life ( GERD-HRQL ) question naire was administered at baseline to patients on and off PPIs , and after placement of the device ; patients served as their own controls . A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs , or a 6-point or more improvement when scores on vs off PPI were compared . RESULTS Over the follow-up period , no device erosions , migrations , or malfunctions occurred . At baseline , the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs ; 5 years after device placement this score decreased to 4 . All patients used PPIs at baseline ; this value decreased to 15.3 % at 5 years . Moderate or severe regurgitation occurred in 57 % of subjects at baseline , but only 1.2 % at 5 years . All patients reported the ability to belch and vomit if needed . Bothersome dysphagia was present in 5 % at baseline and in 6 % at 5 years . Bothersome gas-bloat was present in 52 % at baseline and decreased to 8.3 % at 5 years . CONCLUSIONS Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux , with minimal side effects or complications . No new safety risks emerged over a 5-year follow-up period . These findings vali date the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD . Clinical Trials.gov no : NCT00776997 Abstract Background : As previously reported , the magnetic sphincter augmentation device ( MSAD ) preserves gastric anatomy and results in less severe side effects than traditional antireflux surgery . The final 5-year results of a pilot study are reported here . Patients and Methods : A prospect i ve , multicenter study evaluated safety and efficacy of the MSAD for 5 years . Prior to MSAD placement , patients had abnormal esophageal acid and symptoms poorly controlled by proton pump inhibitors ( PPIs ) . Patients served as their own control , which allowed comparison between baseline and postoperative measurements to determine individual treatment effect . At 5 years , gastroesophageal reflux disease (GERD)-Health Related Quality of Life ( HRQL ) question naire score , esophageal pH , PPI use , and complications were evaluated . Results : Between February 2007 and October 2008 , 44 patients ( 26 males ) had an MSAD implanted by laparoscopy , and 33 patients were followed up at 5 years . Mean total percentage of time with pH < 4 was 11.9 % at baseline and 4.6 % at 5 years ( P < .001 ) , with 85 % of patients achieving pH normalization or at least a 50 % reduction . Mean total GERD-HRQL score improved significantly from 25.7 to 2.9 ( P < .001 ) when comparing baseline and 5 years , and 93.9 % of patients had at least a 50 % reduction in total score compared with baseline . Complete discontinuation of PPIs was achieved by 87.8 % of patients . No complications occurred in the long term , including no device erosions or migrations at any point . Conclusions : Based on long-term reduction in esophageal acid , symptom improvement , and no late complications , this study shows the relative safety and efficacy of magnetic sphincter augmentation for GERD OBJECTIVES : Esomeprazole , the S isomer of omeprazole , has been shown to have higher healing rates of erosive esophagitis than omeprazole . This study compared esomeprazole with lansoprazole for the healing of erosive esophagitis and resolution of heartburn . METHODS : This United States multicenter , r and omized , double blind , parallel group trial was performed in 5241 adult patients ( intent-to-treat population ) with endoscopically documented erosive esophagitis , which was grade d by severity at baseline ( Los Angeles classification ) . Patients received 40 mg of esomeprazole ( n = 2624 ) or 30 mg of lansoprazole ( n = 2617 ) once daily before breakfast for up to 8 wk . The primary efficacy endpoint was healing of erosive esophagitis at week 8 . Secondary assessment s included proportion of patients healed at week 4 , resolution of investigator-recorded heartburn , time to first and time to sustained resolution of patient diary-recorded heartburn , and proportion of heartburn-free days and nights . RESULTS : Esomeprazole ( 40 mg ) demonstrated significantly higher healing rates ( 92.6 % , 95 % CI = 91.5–93.6 % ) than lansoprazole ( 30 mg ) ( 88.8 % , 95 % CI = 87.5–90.0 % ) at week 8 ( p = 0.0001 , life-table estimates , intent-to-treat analysis ) . A significant difference in healing rates favoring esomeprazole was also observed at week 4 . The difference in healing rates between esomeprazole and lansoprazole increased as baseline severity of erosive esophagitis increased . Sustained resolution of heartburn occurred faster and in more patients treated with esomeprazole . Sustained resolution of nocturnal heartburn also occurred faster with esomeprazole . Both treatments were well tolerated . CONCLUSIONS : Esomeprazole ( 40 mg ) is more effective than lansoprazole ( 30 mg ) in healing erosive esophagitis and resolving heartburn . Healing rates are consistently high with esomeprazole , irrespective of baseline disease severity |
11,137 | 20,101,802 | From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid , lower failure , relapse , and acquired drug resistance rates were associated with longer duration of rifampin , use of streptomycin , daily therapy initially , and treatment with a greater number of effective drugs . | Background A st and ardized regimen recommended by the World Health Organization for retreatment of active tuberculosis ( TB ) is widely used , but treatment outcomes are suspected to be poor .
We conducted a systematic review of published evidence of treatment of patients with a history of previous treatment or documented isoniazid mono-resistance . | In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to four 6-month regimens of chemotherapy , all given three times weekly from the start and all containing isoniazid ( H ) and rifampin ( R ) throughout . Three contained streptomycin ( S ) for the first 4 months and pyrazinamide ( Z ) for 2 months ( Z2 ) , 4 months ( Z4 ) , or 6 months ( Z6 ) ; the fourth contained pyrazinamide for 6 months but no streptomycin ( Z6noS ) . Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis . During the later part of the intake patients were allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 125 mg isoniazid , 100 mg rifampin , and 375 mg pyrazinamide , or as the three drugs separately . Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment , bacteriologic failure during chemotherapy occurred in 4 , all Z6noS ( 2 % of 224 ; p less than 0.005 for the comparison with the S-containing regimens ) . During 30 months of follow-up after the end of chemotherapy , bacteriologic relapse occurred in 2 ( 3 % ) of 71 Z2 , 2 ( 3 % ) of 72 Z4 , 4 ( 6 % ) of 66 Z6 , and 6 ( 9 % ) of 64 Z6noS patients allocated to Rifater , and in 4 ( 3 % ) of 149 Z2 , 8 ( 6 % ) of 133 Z4 , 2 ( 1 % ) of 142 Z6 , and 6 ( 4 % ) of 135 Z6noS patients allocated to separate drugs . In the relapse rates there were no significant differences between the Rifater and separate drug regimens , the different duration s of pyrazinamide , or the regimens with and without streptomycin . ( ABSTRACT TRUNCATED AT 250 WORDS The time is now right for r and omized trials of MDR-TB , say the authors , as the expansion of MDR-TB programs provides the setting in which trials can be implemented . In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at r and om to daily chemotherapy with streptomycin , isoniazid , rifampin , and pyrazinamide ( 1 ) for 2 months ( 2SHRZ ) , ( 2 ) for 1 month ( 1SHRZ ) , or ( 3 ) for 2 months without streptomycin ( 2HRZ ) . This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months . During the initial period of daily chemotherapy the patients were also allocated at r and om to be given their HRZ either as a combined formulation ( Rifater ) , each tablet containing 50 mg isoniazid , 120 mg rifampin , and 300 mg pyrazinamide , or as three separate drugs . During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting , reported by 8 % of 155 patients receiving Rifater and 7 % of 155 separate drugs . Other adverse effects were also reported in similar proportions in the two series . Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy . During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 ( 7 % ) of 46 2SHRZ , 2 ( 5 % ) of 42 1SHRZ , and 3 ( 8 % ) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ , 1 ( 2 % ) of 46 1SHRZ , and 1 ( 2 % ) of 44 2HRZ patients allocated to separate drugs . There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ . The relapse rates were slightly higher in the Rifater series ( p = 0.04 ) . Further follow-up and results from other studies are therefore needed fully to assess the combined preparation Five 6-month antituberculosis regimens , allocated at r and om to patients with acid-fast bacilli in their sputum on microscopy , were studied . Four , given three times a week from the start , contained isoniazid and rifampicin together with ( 1 ) streptomycin , pyrazinamide , and ethambutol , ( 2 ) streptomycin and pyrazinamide , ( 3 ) streptomycin and ethambutol , or ( 4 ) pyrazinamide and ethambutol . The fifth was daily isoniazid , rifampicin , pyrazinamide , and ethambutol . All 833 patients with drug-sensitive strains of bacilli before treatment had a favourable bacteriological response during chemotherapy , and the bacteriological relapse rates during 12 months after stopping chemotherapy were 2 % or less for all regimens except thrice-weekly isoniazid , rifampicin , streptomycin , and ethambutol ( the only regimen without pyrazinamide ) , which had a relapse rate of 8 % . The results were equally good for the 138 patients with bacilli resistant to isoniazid , streptomycin , or both drugs initially . The incidence of potentially serious toxicity was low . The daily regimen is relevant to programmes in which patients self-administer their drugs , and the 3 pyrazinamide-containing intermittent regimens are relevant to fully supervised outpatient programmes A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed , sputum-positive pulmonary tuberculosis . The patients were allocated at r and om to one of three regimens : a ) Rifampicin , streptomycin , isoniazid and pyrazinamide daily for 3 months ( R3 ) ; b ) the same regimen as above but followed by streptomycin , isoniazid and pyrazinamide twice-weekly for a further period of 2 months ( R5 ) ; c ) the same as R5 but without rifampicin ( Z5 ) . A bacteriological relapse requiring treatment occurred by 5 years in 16.8 % of 113 R3 , 5.2 % of 97 R5 , and 20.0 % of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially . The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant ( p less than 0.01 for both ) . Considering patients with organisms initially resistant to streptomycin or isoniazid or both , 7 of 52 patients ( 4 R3 , 2 R5 , 1 Z5 ) had a bacteriological relapse requiring retreatment Four short-course antituberculosis regimens allocated at r and om were studied ; ( 1 ) streptomycin , isoniazid , and rifampin given daily for 6 months ; ( 2 ) these 3 drugs plus pyrazinamide given daily for 2 months , followed by twice-weekly administration of streptomycin , isoniazid , and pyrazinamide ; ( 3 ) a regimen that differed from regimen 2 only in that ethambutol replaced pyrazinamide , and ( 4 ) streptomycin plus isoniazid plus rifampin plus pyrazinamide given 3 times per week for 4 months , followed by streptomycin plus isoniazid plus pyrazinamide administered twice per week . The last 3 regimens were given for 6 or 8 months at r and om . All except 1 of 680 patients with tubercle bacilli drug-susceptible before treatment had a favorable bacteriologic response during chemotherapy . The relapse rates during the first 6 months after chemotherapy were low , except in the ethambutol series , in which 19 per cent of the patients relapsed after 6 months of treatment , and 8 per cent relapsed after 8 months . A substantial proportion of the patients with strains initially resistant to either isoniazid or streptomycin had a favorable response to their allocated regimen , but the results were not as good for those patients with strains resistant to both drugs . An important finding is that the incidences of immunologic febrile reactions to rifampin and of rifampin-dependent antibodies were very low during the 3-times-weekly regimen One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared . The daily regimen was rifampicin and ethambutol ( RE7 ) . The three intermittent regimens also contained rifampicin and ethambutol : one of them , rifampicin and ethambutol throughout ( RE3 ) ; the next one supplemented with pyrazinamide for the first 3 months ( REZ3 ) ; the last one supplemented with prothionamide for the first 3 months ( REPt3 ) . The pyrazinamide containing regimen was subdivided into ordinary and high dose groups . The subjects for retreatment were those who have had , at least , more than 6 months of initial triple chemotherapy of isoniazid , PAS and streptomycin at the health centres , and failed to convert to bacteriologically negative status . Among 419 patients who were available for sensitivity tests before commencing retreatment , 393 ( 94.3 % ) were resistant to isoniazid . Six hundred and seventy-four patients ( 674 ) were allocated r and omly to the regimens : 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy . There remain 501 patients who completed their retreatment . As assessed at 12 months , a bacteriologically favourable response was achieved in 68 % of 135 RE7 patients , 62 % of 129 RE3 patients , 74 % of 132 REZ3 patients , and in 79 % of 108 REPt3 patients . Adverse reactions were uncommon : 4 % in RE7 , 5 % in RE3 and 9 % in REZ3 , but 32 % in REPt3 . Relapse rates during 2 years after termination of chemotherapy were 15 % in RE7 , 14 % in RE3 and REZ3 , and 26 % in REPt3 , as calculated by life table analysis This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol ( RHZ and RHE regimens ) against a st and ard daily regimen of streptomycin , isoniazid , and ethambutol ( SHE regimen ) given for 6 months followed by isoniazid and ethambutol for an additional 6 months . Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study . Three hundred and fifty-eight patients were admitted to the study and 267 ( 75 % ) completed chemotherapy . Eighty-five percent of RHZ-regimen and 82 % of RHE-regimen patients achieved sputum culture negativity compared to 55 % of patients in SHE regimen . Successfully treated patients were followed up for 18 months , and among these , all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period . Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period , and no statistically significant difference in relapse rate was noticed in the 3 regimens . Severe drug intolerance necessitated discontinuation of therapy in only 2 patients A total of 481 adult Chinese , Malays , and Indians in Singapore with newly diagnosed smear-positive pulmonary tuberculosis were allocated at r and om to four regimens of intermittent rifampicin plus isoniazid . All patients received an initial 2 weeks of daily streptomycin plus isoniazid plus rifampicin . This was followed either by twice-weekly isoniazid 15 mg/kg plus rifampicin 900 mg ( HR2 regimen ) or 600 mg ( LR2 regimen ) , or by once-weekly isoniazid 15 mg/kg plus rifampicin 900 mg ( HR1 regimen ) or 600 mg ( LR1 regimen ) . In addition , all patients received a daily capsule containing , at r and om , either rifampicin 25 mg or a matched placebo to see if the rifampicin supplement would reduce the incidence of adverse reactions to the drug . At 12 months , all the patients on the two twice-weekly regimens ( HR2 , LR2 ) had a favourable bacteriological status as had 97 % of 102 HR1 and 93 % of 112 LR1 patients . The therapeutic response was significantly better on the twice-weekly than on the once-weekly regimens ( P = 0 - 0005 ) , but the dose size of rifampicin did not have a statistically significant effect . Adverse reactions to intermittent rifampicin occurred in 25 % of the HR1 patients but on the other three regimens their incidence was low . The incidence of rifampicin-dependent antibodies was higher , ranging from 48 % ( HR1 ) to 24 % ( LR2 ) . The effect of dose size on the incidence of the " flu " syndrome ( the commonest reaction ) and of antibodies was statistically significant ( P less than 0 - 01 and less than 0 - 001 , respectively ) . The interval between doses affected the incidence of the " flu " syndrome ( P less than 0 - 001 ) , but not of antibodies ( P greater than 0 - 25 ) . The rifampicin 25 mg supplement had no effect therapeutically or on the incidence of adverse reactions or of antibodies Of 1,019 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on 5 initial microscopic examinations who were studied for 5 yr , 364 ( 36 % ) had 1 or more initial sputum cultures positive for Mycobacterium tuberculosis . All 1,019 patients were r and omly allocated to ( 1 ) selective chemotherapy ( antituberculosis chemotherapy not being started until the disease had been confirmed to be active ) ; or to ( 2 ) daily streptomycin , isoniazid , rifampin , and pyrazinamide for 2 months ; or ( 3 ) for 3 months ; or to ( 4 ) a st and ard 12-month control regimen . In the 364 patients with 1 or more of their initial sputum cultures positive , the short-course regimens were inadequate , being followed by relapse rates of 32 and 13 % , respectively , during 60 months , compared with 5 % in the control series . In the 655 patients with all their initial cultures negative , the corresponding relapse rates were 11 , 7 , and 2 % . In the selective chemotherapy series , 57 % of the patients had treatment started during the 60 months because their disease was confirmed to be active Four daily short-course chemotherapy regimens ( three 6-month and one 8-month ) for pulmonary tuberculosis have been compared . All four had the same initial 2-month intensive phase of streptomycin , isoniazid , rifampicin and pyrazinamide ( SHRZ ) . The continuation phase of the 6-month regimens was : 1 ) isoniazid and rifampicin ( 4HR ) , or 2 ) isoniazid and pyrazinamide ( 4HZ ) , or 3 ) isoniazid alone ( 4H ) and of the 8-month regimen 4 ) isoniazid alone ( 6H ) . All patients have been followed up for 12 months after stopping chemotherapy . In patients with fully sensitive strains pretreatment the 6-month regimen with rifampicin throughout ( 4 HR ) was highly effective with a bacteriological relapse rate of 2 % of 167 patients , significantly better ( P less than 0.01 ) than the rate of 9 % of 158 patients in the 6-month regimen with isoniazid alone in the continuation phase ( 4H ) . The 8-month regimen ( 6H ) was also highly effective , with a relapse rate of 3 % of 119 patients but was not significantly better ( p greater than 0.1 ) than the 6-month isoniazid regimen ( 4H ) . The regimen with pyrazinamide throughout ( 4HZ ) had a relapse rate of 4 % of 165 patients , not significantly different from any of the other regimens . An important finding in the two regimens with isoniazid alone in the continuation phase ( 4H and 6H ) was that 1 of the 2 failures during chemotherapy and 17 of the 18 bacteriological relapses after stopping occurred with strains still sensitive to isoniazid . In patients with strains resistant to isoniazid pretreatment , 8 of 19 patients on the 4H or 6H regimens had an unfavourable response during chemotherapy compared with none of 26 on the HR or HZ regimens ( P less than 0.005 ) . Of the 851 patients who started treatment , 24 developed possible adverse reactions but only 6 required modification of their chemotherapy A r and omised controlled trial compared the effectiveness and toxicity in pulmonary tuberculosis of two drug regimens containing rifampicin and isoniazid given daily or twice-weekly for 4 months after a 2-month period of intensive treatment with daily isoniazid , rifampicin , and pyrazinamide . 667 patients with newly diagnosed pulmonary tuberculosis were r and omly allocated to continue daily treatment with isoniazid ( 400 mg ) and rifampicin ( 600 mg ) or to twice-weekly treatment with isoniazid ( 900 mg ) and rifampicin ( 600 mg ) . 544 of the 667 patients ( 81 % ) completed the 6-month course ( 287 of 337 [ 85 % ] treated daily and 257 of 330 [ 79 % ] treated twice-weekly ) . Drug toxicity was not a great problem ; the treatment was permanently discontinued in only 2 % of patients . There was no significant difference at the end of months 5 and /or 6 of chemotherapy between the groups treated daily and twice-weekly in the proportions with bacteriological failure ( at least one positive sputum culture with more than 20 colonies ) or who had died from tuberculosis ( 17 [ 6 % ] vs 10 [ 3 % ] ) . Nor was there a significant difference in the relapse rate ( 17 [ 7 % ] treated daily vs 10 [ 4 % ] treated twice-weekly ) during follow-up of 12 months . Thus , the twice-weekly regimen was at least as effective as the daily regimen for treatment of pulmonary tuberculosis In a study in Singapore , Chinese , Malay and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin , isoniazid , rifampicin , and pyrazinamide followed by daily isoniazid , and rifampicin either with pyrazinamide ( SHRZ/HRZ ) or without it ( SHRZ/HR ) , allocated at r and om . Both regimens were given for either 6 or 4 months by r and om allocation . All 330 patients with drug-sensitive tubercle bacilli pretreatment had a favourable bacteriological response during chemotherapy . After chemotherapy none of 78 SHRZ/HRZ patients and only 2 of 80 SHRZ/HR patients treated for 6 months relapsed bacteriologically , but 9 ( 11 % ) of 79 SHRZ/HRZ and 6 ( 8 % ) of 77 SHRZ/HR patients treated for 4 months relapsed . Of 33 patients with bacilli resistant to isoniazid , streptomycin , or both drugs pretreatment , only 1 had an unfavourable response during chemotherapy ; none of 9 patients treated for 6 months and 2 of 22 treated for 4 months relapsed bacteriologically after stopping chemotherapy Of 1,710 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on four or more initial microscopic examinations who were studied for 5 yr , 592 ( 35 % ) had one or more initial sputum cultures positive for Mycobacterium tuberculosis . These 592 patients were r and omly allocated to receive streptomycin , isoniazid , rifampin , and pyrazinamide daily for 4 months or 3 times a week for either 4 or 6 months . The remaining 1,118 patients with all their initial cultures negative were r and omly allocated to receive the same four drugs daily for 3 months or 3 times a week for either 3 or 4 months . There were no bacteriologic failures during chemotherapy , and the relapse rates for the 4-month regimens during the 5 yr were 2 % in 293 patients with drug-susceptible cultures initially ( 95 % confidence limits , 1 to 5 % ) ; 8 % in 59 patients with cultures resistant to isoniazid , streptomycin , or both drugs , but susceptible to rifampin initially ; and 4 % in 325 patients with all their cultures negative initially ( 95 % confidence limits , 1 to 7 % ) . The combined relapse rate for the 3-month regimens was 7 % in 709 patients with all their cultures negative initially ( 95 % confidence limits , 5 to 9 % ) . In Hong Kong , 4 months of chemotherapy is now used routinely in the treatment of patients with smear-negative pulmonary tuberculosis , whether their initial sputum cultures are positive or negative Patients with silicotuberculosis have been reported to respond poorly to antituberculosis chemotherapy . Therefore , in a study in Hong Kong , 240 Chinese male patients with both silicosis and pulmonary tuberculosis were all prescribed treatment three times weekly with streptomycin , isoniazid , rifampin , and pyrazinamide , allocated at r and om to be given for a total duration of either 6 ( M6 regimen ) or 8 months ( M8 regimen ) in a concurrent comparison . Those with a history of previous antituberculosis chemotherapy received ethambutol as well for the first 3 months . The intake in the M6 regimen was terminated when preliminary results showed that it was inadequate , and a further 53 patients were assigned to the M8 series . Of 91 assessable patients in the concurrent comparison with susceptible strains pretreatment , 44 % were culture negative at 1 month , 80 % at 2 months , and 98 % at 3 months , and 1 had an unfavorable bacteriologic response during chemotherapy . During 3 yr of assessment , bacteriologic relapse after chemotherapy occurred in 22 % of the M6 compared with 7 % of the M8 patients ( p less than 0.025 , log-rank test ) . Inadequate chemotherapy was received by 12 % of the 240 patients in the concurrent comparison because of default and by 22 % because of adverse effects , but by 3 yr 92 % of patients with susceptible strains pretreatment in each series had a favorable status following retreatment for relapse or for initially inadequate chemotherapy when required . The results show that patients with silicosis require at least 8 months of treatment Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at r and om to receive a regimen of rifampicin and ethambutol for 6 ( 4RE ) or 9 months ( 7RE ) , supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months . The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community . A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy , 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin . There were only two failures at the end of chemotherapy , one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment , and one in the 9-month series who had resistance to isoniazid alone . For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months , the relapse rates were low in both series : 4 % for the 72 patients in the 6-month series and 3 % for the 72 patients in the 9-month series . However , for the 34 patients with resistance to both drugs , three of the 14 in the 6-month but none of 20 in the 9-month series relapsed In a study in Singapore , Chinese , Malay , and Indian patients with sputum-smear-positive pulmonary tuberculosis were allocated at r and om to daily treatment with streptomycin , isoniazid , rifampin , and pyrazinamide for 2 months ( 2SHRZ ) , 1 month ( 1SHRZ ) , or 2 months without streptomycin ( 2HRZ ) , followed , for all patients , by 3-times-weekly isoniazid and rifampin ( H3R3 ) up to 6 months . At 2 months , the culture-negativity rate for the 2SHRZ series was statistically significantly higher than for either of the other 2 series . All 319 patients with drug-sensitive tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy except for one 2SHRZ/H3R3 patient , and among the 300 patients assessed during 24 months of follow-up after chemotherapy there was only 1 bacteriologic relapse in each series , giving an overall therapeutic failure rate of only 1 % . Thus , the 2SHRZ combination had the highest early sterilizing activity , but the potent continuation therapy compensated for the initial inferiority of the other 2 regimens . Among the 32 patients with tubercle bacilli resistant pretreatment to isoniazid , streptomycin , or both drugs , there were no failures during chemotherapy and 3 subsequent relapses among the 30 assessed during 24 months of follow-up . Eleven ( 3 % ) of the 420 patients who started chemotherapy on their allocated regimen had hepatitis with jaundice during chemotherapy . However , 2 of these had cirrhosis pretreatment and 1 was a chronic alcoholic OBJECTIVE To evaluate the efficacy of split-drug regimens for treatment of patients with sputum smear-positive pulmonary tuberculosis in south India . DESIGN R and omized controlled clinical trial where eligible patients were r and omly allocated to : ( i ) 2RE(3)HZ(3)(alt)/4RH(2 ) ( split I ) : rifampicin plus ethambutol given on one day and isoniazid plus pyrazinamide the next day for first 2 months followed by rifampicin plus isoniazid twice weekly for 4 months , or ( ii ) 3RE(3)HZ(3)(alt)/3RH(2 ) ( split II ) : similar to regimen 1 , except duration was 3 months in each phase , or ( iii ) 2REHZ(3)/4RH(2 ) ( control ) : rifampicin , isoniazid , ethambutol and pyrazinamide , given thrice weekly for 2 months followed by isoniazid and rifampicin twice weekly for 4 months . All patients were followed up clinical ly and bacteriologically every month up to 2 years and every 6 months for up to 5 years . RESULTS A favourable response ( cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment ) was observed in 91 % of 407 patients in split I , 94 % of 415 in split II and 89 % of 418 in the control regimen . Ninety-one per cent of 370 patients in split I , 93 % of 389 in split II and 90 % of 370 in control regimens had quiescent disease at the end of 60 months . Gastrointestinal symptoms were more frequent under the control regimen ( P = 0.01 ) . CONCLUSION Split-drug regimens were as effective as the control regimen in terms of favourable response at the end of treatment and quiescent disease at 5 years , and caused fewer gastrointestinal side-effects In a study in Singapore , Chinese , Malay , and Indian patients with pulmonary tuberculosis received 2 months of daily treatment with streptomycin , isoniazid , rifampin , and pyrazinamide followed either by daily treatment with isoniazid , rifampin , and pyrazinamide ( SHRZ/HRZ regimen ) or by daily administration of isoniazid and rifampin ( SHRZ/HR regimen ) allocated at r and om . Both regimens were given for either 6 or 4 months by r and om allocation . All 330 patients with drug-sensitive tubercle bacilli before treatment had a favorable bacteriologic response during chemotherapy . During the first 6 months after the end of chemotherapy , there was only a single bacteriologic relapse among 84 SHRZ/HRZ and 80 SHRZ/HR patients treated for 6 months , but 8 ( 10 per cent ) of 80 SHRZ/HRZ and 4 ( 5 per cent ) of 74 SHRZ/HR patients treated for 4 months relapsed . Of a total of 33 patients with bacilli resistant to isoniazid , streptomycin , or both drugs before treatment , only one had an unfavorable response during chemotherapy , and none of 31 patients relapsed during the first 6 months after stopping chemotherapy . The incidence of adverse reactions was low ; 11 ( 3 per cent ) of 397 patients had hepatitis , but not all episodes were attributable to drug toxicity , and one patient had thrombocytopenic purpura Three hundred and twenty-nine patients with isoniazid-resistant cultures , 66 % with radiographically far advanced disease and 86 % with cavities , have been treated with rifampicin and ethambutol and followed-up for 2 years after the end of treatment . The drugs were given daily for 12 weeks ( 600 mg rifampicin and 25 mg/kg ethambutol ) , thereafter once- or twice-weekly ( 600 or 1200 mg rifampicin and 50 mg/kg ethambutol ) for a total of 12 , 18 or 24 months ( in the 600 mg group for 12 months only ) . With both 600 and 1200 mg rifampicin dosage the bacteriological results at the end of a year were similar ( 5 % bacteriologically unfavourable in each group ) . Prolonging treatment to 18 or 24 months with the 1200 mg rifampicin dose had no effect on the bacteriological results . During the 2 years follow-up period after treatment stopped 6 patients had a bacteriological relapse . Of the 74 with a favourable status after 1 year in the 600 mg rifampicin group 5 ( 6.7 % ) relapsed , but only 1 ( 0.6 % ) of 168 in the 1200 mg groups treated for 12 , 18 or 24 months ( the duration of treatment did not appear to be related to relapse ) . Side-effects were reported more frequently with once-weekly dosage . They were more frequent with 1200 mg rifampicin than with 600 mg and with the former dose more frequent in the groups treated for longer than 1 year . With 12 months treatment with 600 mg rifampicin only 1 % of patients had to have the regimen changed ; with 1200 mg it was 9 % and with this dose for 24 months 20 % . With the lower dosage of rifampicin there were fewer failures due to toxicity but more failures due to relapse . Of 82 patients in the 600 mg regimen there were 12 % unfavourable results ( 4 bacteriological failures , 5 relapses and 1 change of treatment for toxicity ) . Of 78 patients in the 1200 mg regimen there were 13 % unfavourable results ( 3 bacteriological failures , no relapses and 7 changes of treatment for toxicity ) |
11,138 | 21,080,841 | In addition , a shorter expulsion time , lower analgesic requirements , fewer colic episodes and adverse effects were observed .
CONCLUSIONS Tamsulosin is a safe and effective therapy for renal and ureteral stones after SWL . | OBJECTIVE This study aim ed to evaluate the efficacy of tamsulosin as an α(1)-blocker in the treatment of the renal and ureteral stones after shockwave lithotripsy ( SWL ) . | PURPOSE We evaluated the effect of the alpha-blocker tamsulosin on stone clearance , analgesic requirements and steinstrasse in shock wave lithotripsy for solitary renal and ureteral calculus . MATERIAL S AND METHODS A prospect i ve , double-blind , r and omized placebo controlled study was performed during 1 year involving 60 patients with a solitary renal or ureteral calculus undergoing shock wave lithotripsy . The control group ( 30 ) received 0.4 mg tamsulosin and the study group ( 30 ) received placebo daily until stone clearance or for a maximum of 30 days . An oral preparation of dextropropoxyphene hydrochloride and acetaminophen was the analgesic used on an on-dem and basis . The parameters assessed were stone size , position , clearance time , effect on steinstrasse and analgesic requirement . RESULTS The overall clearance rate was 96.6 % ( 28 of 29 ) in the study group and 79.3 % ( 23 of 29 ) in the control group ( p = 0.04 ) . With larger stones 11 to 24 mm the difference in the clearance rate was significant ( p = 0.03 ) but not so with the smaller stones 6 to 10 mm ( p = 0.35 ) . The average dose of analgesic used was lower with tamsulosin than with controls , without statistical significance . Steinstrasse resolved spontaneously in the tamsulosin group whereas 25 % ( 2 of 8) required intervention in the placebo group . There was no difference between the 2 groups with regard to age , stone size or location . CONCLUSIONS The alpha-blocker tamsulosin seemed to facilitate stone clearance , particularly with larger stones during shock wave lithotripsy for renal and ureteral calculus . It also appeared to improve the outcome of steinstrasse . Tamsulosin may have a potential role in routine shock wave lithotripsy OBJECTIVES To design a r and omized , no-treatment , controlled , prospect i ve study to determine whether the administration of tamsulosin , as adjunctive medical therapy , increases the efficacy of one extracorporeal shock wave lithotripsy ( ESWL ) session to treat renal stones and decreases the use of analgesic drugs after the procedure . METHODS A total of 130 patients underwent a single ESWL session to treat solitary radiopaque renal stones 4 to 20 mm in diameter . After treatment , all patients were r and omly assigned to receive our st and ard medical therapy alone ( controls ) or in association with 0.4 mg tamsulosin daily for a maximum of 12 weeks . All 130 patients were followed up for 3 months or until an alternative treatment was given . RESULTS Of the 130 patients , 78.5 % of those receiving tamsulosin and 60 % of controls had achieved clinical success at 3 months ( P = 0.037 ) . When we stratified patients according to stone size , for those with a stone size larger than 10 mm , the success rate was significantly greater in the tamsulosin group ( P = 0.028 ) . Renoureteral colic occurred in 76.9 % of patients treated with st and ard therapy but in only 26.1 % of those receiving tamsulosin ( P < 0.001 ) . The mean cumulative diclofenac dose was 375 mg per patient in the tamsulosin group and 675 mg per patient in the control group ( P < 0.001 ) . CONCLUSIONS The results of our study have demonstrated that tamsulosin therapy , as an adjunctive medical therapy after ESWL , is more effective than lithotripsy alone for the treatment of patients with large renal stones and is equally safe . In addition , our results also indicated that adjunctive treatment with tamsulosin could decrease the use of analgesic drugs after ESWL Extracorporeal shock wave lithotripsy ( ESWL ) is currently considered one of the main treatments for ureteral stones . Some studies have reported the effectiveness of pharmacologic therapies ( calcium antagonists or alpha-blockers ) in facilitating ureteral stone expulsion after ESWL . We prospect ively evaluated the efficacy , after ESWL , of nifedipine on upper-middle ureteral stones , and tamsulosin on lower ureteral stones , both associated to ketoprofene as anti-edema agent . From January 2003 to March 2005 we prospect ively evaluated 113 patients affected by radiopaque or radiolucent ureteral stones . Average stone size was 10.16 ± 2.00 mm ( range 6–14 mm ) . Thirty-seven stones were located in the upper ureter , 27 in the middle ureter , and 49 in the lower ureter . All patients received a single session of ESWL ( mean number of shock waves : 3,500 ) by means of a Dornier Lithotripter S ( mean energy power for each treatment : 84 % ) . Both ultrasound and X-ray were used for stone scanning . After treatment , 63 of 113 patients were su bmi tted to medical therapy to aid stone expulsion : nifedipine 30 mg/day for 14 days administered to 35 patients with upper-middle ureteral stones ( group A1 ) and tamsulosin 0.4 mg/day for 14 days administered to 28 patients with stones located in the distal ureter ( group A2 ) . The remaining 50 patients were used as a control group ( 29 upper – middle ureteral stones — B1— and 21 lower ureteral stones — B2— ) , receiving only pain-relieving therapy . No significant difference in stone size between the groups defined was observed . Stone clearance was assessed 1 and 2 months after ESWL by means of KUB , ultrasound scan and /or excretory urography . A stone-free condition was defined as complete stone clearance or the presence of residual fragments smaller than 3 mm in diameter . The stone-free rates in the expulsive medical therapy group were 85.7 and 82.1 % for the nifedipine ( A1 ) and tamsulosin ( A2 ) groups respectively ; stone-free rates in the control groups were 51.7 and 57.1 % ( B1 and B2 , respectively ) . Five patients ( 14.3 % ) in group A1 , 5 ( 17.8 % ) in group A2 , 14 ( 48.3 % ) in group B1 and 9 ( 42.8 % ) in group B2 were not stone-free after a single ESWL session and required ESWL re-treatment or an endoscopic treatment . Medical therapy following ESWL to facilitate ureteral stone expulsion results in increased 1- and 2-month stone-free rates and in a lower percentage of those needing re-treatment . The efficacy of nifedipine for the upper-mid ureteral tract associated with ketoprofene makes expulsive medical therapy suitable for improving overall outcomes of ESWL treatment for ureteral stones OBJECTIVES To investigate the role of tamsulosin as an adjunct to management of upper ureteric stones ( UUS ) with extracorporeal shock wave lithotripsy ( SWL ) . METHODS In this prospect i ve , r and omized , open label study , patients with single UUS ( for SWL ) were r and omly assigned into 2 groups based on whether they received 0.4 mg tamsulosin ( group A and B , respectively ) during treatment . Repeat SWL was performed at week 1 , 3 , and 5 after first session . Primary outcome variables were success rate and pain intensity . RESULTS A total of 40 patients ( 20 each group ) completed the requisite follow-up . Success rate was higher in group A after 1 SWL-session ( 55 % vs 25 % , respectively ; P = .05 ) . There was an insignificant trend of decreased number of days ( 30.7 + /- 19.7 vs 39.0 + /- 19.9 ; P = .19 ) , number of SWL sessions ( 1.6 vs 2.0 ; P = .10 ) , and pain experienced ( score on visual analog scale , 25.3 + /- 17.9 vs 38.3 + /- 28.0 , respectively ; P = .41 ) in group A. Three in group A and 6 in B developed steinstrasse ( P = .69 ) . Overall , 1 in group A required auxiliary procedures as compared with 3 in control group ( P = .60 ) . CONCLUSIONS Tamsulosin improves clearance rate of UUS after single SWL . However , it does not provide significant advantage in terms of decreasing pain associated with this treatment OBJECTIVES To evaluate whether alpha1-blockers have any impact on stone clearance in patients with lower ureteral stones who underwent either shock wave lithotripsy ( SWL ) or were followed up with st and ard hydration , analgesics , and anti-inflammatory treatment . METHODS A total of 78 patients ( 56 men and 22 women ) who had lower ureteral stones located at the distal 5 cm of the ureter were divided into four groups . The first group consisted of 30 patients ( 38.5 % ) with stones less than 5 mm ( range 3 to 5 ) who were r and omly divided into two subgroups . Group 1 consisted of 15 patients ( 19.2 % ) who were followed up with oral hydration and diclofenac sodium . Group 2 consisted of 15 patients ( 19.2 % ) who received tamsulosin 0.4 mg daily in addition to the st and ard regimens . The second two groups consisted of 48 patients ( 61.5 % ) with stones greater than 5 mm ( range 6 to 15 ) who underwent SWL . These patients were also r and omly divided between those who did not ( group 3 , n = 24 ) and those who did ( group 4 , n = 24 ) receive tamsulosin 0.4 mg daily . All patients were re-evaluated with plain abdominal x-rays and helical computed tomography 15 days after the beginning of treatment . RESULTS Of the 78 patients , 36 ( 46.2 % ) became stone free . The stone-free rate was 20 % , 53.3 % , 33.3 % , and 70.8 % for group 1 , 2 , 3 , and 4 , respectively . The best results were achieved in those who underwent SWL plus tamsulosin treatment ( group 4 ) . The differences between the stone-free rates for groups 3 versus 4 ( P = 0.019 ) and the tamsulosin versus control groups ( P = 0.0015 ) were statistically significant . CONCLUSIONS The addition of tamsulosin to conventional treatment seemed beneficial in terms of stone clearance of lower ureteral stones , and this effect was more evident for larger stones , especially when combined with SWL OBJECTIVE To evaluate the efficacy of alpha1-adrenergic antagonist in the medical management of lower ureteral stone with extracorporeal shock wave lithotripsy ( ESWL ) . METHODS A total of 80 patients with stone located in lower ureter were r and omly divided into two groups . Group 1 served as control and group 2 received tamsulosin ( 0.4 mg , once daily ) after ESWL . All patients were observed for 2 weeks and asked to compile a diary about renal colic , stone expulsion , use of analgesic drugs , and side effects of medical therapy . RESULTS During 2 weeks , stones were expulsed in 18 patients ( 45.0 % ) of group 1 and in 31 patients ( 77.5 % ) of group 2 . The expulsion rate between group 1 and group 2 was significantly different ( P < 0.01 ) . Eight patients ( 20.0 % ) in group 1 and 2 patients ( 5.0 % ) in group 2 experienced renal colic relapse within 2 weeks and were administered with analgesics ( P < 0.05 ) . No side effect in group 1 was reported , except that 2 patients in group 2 complained of slight dizziness . CONCLUSIONS Tamsulosin ( alpha1-adrenergic antagonist ) can improve the stone-free rate of lower ureteral stones after ESWL and reduce the relapse of renal colic . As a safe and effective agent , it can be regarded as an auxiliary clearance method after ESWL for lower ureteral stones Introduction : We assessed the efficacy of using an α-1A-specific blocker for improving the success rate in shock wave lithotripsy ( SWL ) for lower ureteral stones . Material s and Methods : This prospect i ve study was conducted from June 2005 to December 2006 and involved 107 patients . All the patients underwent SWL with the PCK Stonelith . The patients were r and omly divided into 3 groups : group 1 ( 34 patients ) received tamsulosin , group 2 ( 35 patients ) received terazosin , and group 3 ( 38 patients ) received placebo . All patients were diagnosed by kidney-ureter-bladder X-ray , abdominal ultrasonography and intravenous urography . The number of colic episodes , lower urinary tract symptoms , analgesic dosage and days for spontaneous passage of the stones through the ureter were recorded by diary . Statistical analyses were performed using ANOVA , the χ2 test , Fisher ’s exact test and the non-parametric Wilcoxon 2- sample t test . Results : There were no differences between the groups regarding age , stone size , expulsion time and expulsion rate . The number of colic episodes and the analgesic dosage were significantly lower in group 1 compared with groups 2 and 3 . A statistically significant difference was observed in lower urinary tract symptoms : lower urinary tract symptoms were observed in 4 of 34 patients in group 1 ( 12 % ) , in 8 of 35 in group 2 ( 23 % ) , and in 13 of 38 in group 3 ( 34 % ) . Adverse effects were noted in 5 of 32 patients in group 2 ( 16 % ) , which was significantly different in comparison with group 3 . Conclusions : Administration of an α-1A-specific blocker reduced analgesic dosage and colic episodes after SWL of lower ureteral stones . There was no benefit with regard to increasing stone expulsion rate or decreasing expulsion time Our study aim ed to define the position of tamsulosin as adjunctive therapy in patients with stones of the distal ureter who had undergone extracorporeal shock wave lithotripsy ( ESWL ) . In total , 61 consecutive patients ( 38 men and 23 women ) with single distal radiopaque ureteral stone of ≥6 mm of diameter were enrolled . After ESWL patients were r and omized in two groups . Non-steroidal anti-inflammatory drug ( supp . diclofenac 50 mg ) was given to both groups upon dem and . In group B , all patients ( 30 ) received additionally tamsulozin 0.4 mg every day . Follow-up visits were performed 1 , 2 , 3 and 4 weeks after ESWL . Evaluation included a KUB plain film and an ultrasound examination . Efficacy was evaluated in terms of success rate , stone-free rate , expulsion time of the fragments and use of diclofenac . Two patients from the tamsulosin group experienced dizziness and one was withdrawn . The success rate was 58.06 and 66.66 % for the control and the tamsulosin group , respectively , while the corresponding values for stone-free rate were 51.6 and 63.33 % , respectively . The mean expulsion time of the fragments was 13.22 days for group A and 12.95 days for group B. These results did not achieve statistically significant difference ( P > 0.05 ) . The mean diclofenac dose was 118.9 mg in group A and 56.9 mg in group B. This difference was statistically significant ( P = 0.02 ) . Despite the relatively small number of patients , our data indicate that the use of tamsulosin after ESWL in this specific subgroup of patients does not result in improved success and stone-free rate and expulsion time . In contrast , a significantly reduced need for analgesics was found OBJECTIVES To increase the success rate of the first treatment of ureteral stones through extracorporeal shock wave lithotripsy ( ESWL ) , we tested the efficacy of a medical therapy with nifedipine and deflazacort administered to patients who had undergone ESWL for ureteral stones . METHODS This prospect i ve study lasted from October 1998 to September 2000 and involved 80 patients . All the patients underwent ESWL with Sonolith 4000 + . The patients were r and omly divided into two groups : 40 patients ( group 1 ) received an " adjunctive " treatment with oral medical therapy ( nifedipine and deflazacort ) ; the other 40 patients ( group 2 ) were used as the control group . RESULTS Complete fragment expulsion occurred in 30 ( 75 % ) of the 40 patients of group 1 and in 20 ( 50 % ) of the 40 patients of group 2 at the endpoint . A statistically significant difference was observed in the stone-free rate ( P = 0.02 ) . Concerning the symptomatic therapy , the average diclofenac use was 37.5 mg per patient in group 1 and 86.25 mg per patient in group 2 ( P = 0.02 ) . CONCLUSIONS The results of this study have shown the role that adjunctive medical therapy with nifedipine and deflazacort given after an ESWL procedure can play in increasing the success rate of ureteral stone treatment . Furthermore , these results would suggest that adjunctive medical therapy can reduce total analgesic consumption after the ESWL procedure OBJECTIVE We evaluated the efficacy of low dose tamsulosin after extracorporeal shock wave lithotripsy ( ESWL ) in Japanese male patients with ureteral stone . METHODS One hundred and two Japanese male patients with ureteral stones who underwent ESWL were r and omly divided into three groups . Group A ( 38 patients ) was given tamsulosin ( 0.2 mg/day ) ; group B ( 30 patients ) was given c horeito , a herbal medicine ( 7.5 g/day ) ; and group C ( 34 patients ) received no medication . Stone clearance was assessed at 1 , 7 , 14 , and 28 days after ESWL using plain abdominal radiography and abdominal ultrasonography . After 28 days , stone delivery was checked every 2 weeks . RESULTS The stone-free rate was 84.21 % , 90 % , and 88.24 % for groups A , B , and C , respectively ( P = 0.3425 ) . The mean expulsion time was 15.66 + /- 6.14 days in group A , 27.74 + /- 25.36 days in group B , and 35.47 + /- 53.70 days in group C. The expulsion time of group A was significantly shorter than that of groups B ( P = 0.0116 ) and C ( P = 0.0424 ) . CONCLUSIONS The addition of tamsulosin to conservative treatment appeared to be effective in shortening the stone expulsion time OBJECTIVES To evaluate the role of tamsulosin in the clearance of fragments after extracorporeal shock wave lithotripsy ( ESWL ) to treat renal calculi . METHODS In this open-label prospect i ve r and omized study conducted at our institute from 2006 to 2007 , 139 patients with normal renal function and a single radiopaque renal calculus , 5 - 20 mm , undergoing ESWL were enrolled . All patients underwent ESWL every 3 weeks until success or for < or=3 months , whichever was earlier . They were r and omly assigned to 2 groups with respect to whether they had received tamsulosin , 0.4 mg/d . The primary endpoint was the success rate , and the secondary endpoints were clearance time , sessions required for clearance , pain intensity , incidence of steinstrasse , and the need for auxiliary procedures . RESULTS Of the 139 patients , 51 in group 1 and 65 in group 2 completed the requisite follow-up . The demographic profile of both groups was comparable . The success rate after 1 , 2 , and 3 ESWL sessions was greater in group 1 than in group 2 ( 52.9 % , 78.4 % , and 94.1 % vs 30.8 % , 52.3 % , and 75.4 % ; P = .016 , P = .004 , and P = .007 , respectively ) . The total days required for success ( 35.53 + /- 19.47 vs 47.22 + /- 23.64 ; P = .006 ) , total ESWL sessions required for success ( 1.66 vs 2.16 ; P = .005 ) , and the pain experienced ( visual analog scale score 28.67 + /- 20.35 vs 47.30 + /- 24.98 , respectively ; P = .0001 ) were significantly less in group 1 . Two patients in group 1 and 9 in group 2 developed steinstrasse ( P = .10 ) ; conservative management was successful in 1 patient in each group ( P = .345 ) . Three patients in group 1 and 10 in group 2 required auxiliary procedures ( P = .14 ) . CONCLUSIONS The results of our study have shown that tamsulosin facilitates earlier clearance of fragments after ESWL to renal calculi and helps reduce the severity of the pain . It tended to facilitate spontaneous clearance of steinstrasse ; however , this requires additional evaluation |
11,139 | 21,157,845 | A small group workshop and a decision support system ( DSS ) increased dementia detection rates .
Adherence to dementia guidelines only improved when an educational intervention was combined with the appointment of dementia care managers .
This combined intervention also improved patients ' and caregivers ' quality of life .
Effects on knowledge and attitudes were minor .
Educational interventions for PCPs that require active participation improve detection of dementia .
Educational interventions alone do not seem to increase adherence to dementia guidelines . | OBJECTIVE To determine the effects of educational interventions about dementia , directed at primary care providers ( PCPs ) . | Background Early diagnosis of dementia benefits both patient and caregiver . Nevertheless , dementia in primary care is currently under-diagnosed . Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff . However , none of these interventions focussed on collaboration between GPs and nurses in dementia care . We developed an EASYcare-based Dementia Training Program ( DTP ) aim ed at stimulating collaboration in dementia primary care . We expect this program to increase the number of cognitive assessment s and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses . Methods The DTP is a complex educational intervention that consists of two workshops , a coaching program , access to an internet forum , and a Computerized Clinical Decision Support System on dementia diagnostics . One hundred duos of GPs and nurses will be recruited , from which 2/3 will be allocated to the intervention group and 1/3 to the control group . The effects of implementation of the DTP will be studied in a cluster-r and omised controlled trial . Primary outcomes will be the number of cognitive assessment s and dementia diagnoses in a period of 9 months following workshop participation . Secondary outcomes are measured on GP and nurse level : adherence to national guidelines for dementia , attitude , confidence and knowledge regarding dementia diagnosis and management ; on patient level : number of emergency calls , visits and consultations and patient satisfaction ; and on caregiver level : informal caregiver burden and satisfaction . Data will be collected from GPs ' electronic medical records , self- registration forms and question naires . Statistical analysis will be performed using the MANOVA- method . Also , exploratory analyses will be performed , in order to gain insight into barriers and facilitators for implementation and the possible causal relations between the rate of success of the intervention components and the outcomes . Discussion We developed multifaceted dementia training programme . Novelties in this programme are the training in fixed collaborative duos and the inclusion of an individual coaching program . The intervention is design ed according to international guidelines and educational st and ards . Exploratory analysis will reveal its successful elements . Selection bias and contamination may be threats to the reliability of future results of this trial . Nevertheless , the results of this trial may provide useful information for policy makers and developers of continuing medical education . Trial registration Clinical Trials.gov ID Abstract Objective To test the effectiveness of educational interventions in improving detection rates and management of dementia in primary care . Design Unblinded , cluster r and omised , before and after controlled study . Setting General practice s in the United Kingdom ( central Scotl and and London ) between 1999 and 2002 . Interventions Three educational interventions : an electronic tutorial carried on a CD Rom ; decision support software built into the electronic medical record ; and practice based workshops . Participants 36 practice s participated in the study . Eight practice s were r and omly assigned to the electronic tutorial ; eight to decision support software ; 10 to practice based workshops ; and 10 to control . Electronic and manual search es yielded 450 valid and usable medical records . Main outcome measures Rates of detection of dementia and the extent to which medical records showed evidence of improved concordance with guidelines regarding diagnosis and management . Results Decision support software ( P = 0.01 ) and practice based workshops ( P = 0.01 ) both significantly improved rates of detection compared with control . There were no significant differences by intervention in the measures of concordance with guidelines . Conclusions Decision support systems and practice based workshops are effective educational approaches in improving detection rates in dementia Implementation of clinical practice guidelines has been proposed to improve quality in health care . Multifaceted implementation did not increase guideline acceptance . GPs ' self-reports may overestimate performance . Objective - To assess the impact of a multifaceted implementation strategy aim ing to improve GP adherence to a clinical guideline on dementia . Design - Controlled before and after study using data records from regional laboratories . The guideline was mailed to all GPs . The multifaceted implementation strategy was planned with local GPs , and consisted of seminars , outreach visits , reminders and continuing medical education ( CME ) small group training . Setting - Primary health care . Subjects - 535 GP practice s with 727 physicians in Denmark . Main outcome measures - The diffusion and use of the guideline was measured by a mailed survey . Adherence to guideline recommendations was monitored by data on laboratory tests from general practice in patient 's S 65 years : thyroid stimulating hormone requested with vitamin B 12 or methylmalonate . The use of these tests as part of a diagnostic evaluation of dementia was subsequently verified by a question naire to the practice s. Results - Of the GPs who read the guideline , 88 % found it applicable in primary care . No increase in the adherence to guideline recommendations was observed regarding the use of laboratory tests or cognitive tests in the diagnostic evaluation of dementia in general practice . Conclusion - Although GPs regarded the guideline applicable in primary care , no change in practice adherence to guideline recommendations was detected after a multifaceted implementation Context Dementia is an incurable chronic disease , but assistance to caregivers can reduce the severity of patients ' symptoms and delay institutionalization . Because this assistance requires provision of multiple health care and social services , patients and caregivers might benefit from a coordinated system of care . Contribution The investigators r and omly assigned patients with dementia and their caregivers to usual care or to a coordinated system of care . In the coordinated system , care managers regularly assessed patient and caregiver pairs and coordinated guideline -recommended provision of services by health care providers and community agencies using computerized information systems . The study found that pairs cared for in the coordinated system received higher- quality health care and more needed assistance than those who received usual care . Caution s The study focused on a relatively homogeneous population of white , well-educated , otherwise healthy , noninstitutionalized patients with health insurance . The findings might not apply to other population s. Implication s The quality of care for patients with dementia and their caregivers can be improved with a model of care in which services provided by the health system and community agencies are coordinated by a care manager . The Editors Dementia has enormous health and financial consequences for affected individuals , their family caregivers , and society ( 15 ) . Although most dementia is currently neither preventable nor reversible , existing practice guidelines reflect evidence from r and omized , controlled trials that caregiver assistance and support can delay institutionalization ( 68 ) , and nonpharmacologic management of problem behaviors and depression can reduce symptom severity and improve patient health ( 9 , 10 ) . Yet , adherence to published dementia care guidelines ( 1114 ) is poor ( 15 ) , including inappropriate use of psychoactive medications for initial management of agitation ( 16 ) ; low referral rates to community agencies ( 17 , 18 ) ; and underdetection of elder abuse , for which cognitive impairment is a risk factor ( 19 ) , and of depression ( 20 ) , a common comorbid condition ( 21 ) . There are few controlled trials of improvement interventions for dementia care . An opinion leader intervention improved neurologists ' reported adherence to dementia care guidelines ( 18 ) , and a recent trial using advanced practice nurses within primary care improved care quality ( 22 ) ; other trials reported limited impacts ( 23 , 24 ) . All studies were conducted primarily within or outside of health care delivery systems ; to date , trials of comprehensive , guideline -based dementia care interventions that incorporate all chronic care model components , including substantive collaboration between health systems and community agencies ( 25 , 26 ) , have not been reported . Yet , this would seem to be a well-suited approach because of the multifaceted nature of dementia care management and the need for coordinated efforts across health care delivery systems and community agencies to provide recommended medical , behavioral , and social services and support . To address gaps in care quality for persons with dementia , we design ed and tested a guideline -based , comprehensive dementia care management intervention in a clinic-level , cluster r and omized , controlled trial ( 27 ) . Intervention components were based on the chronic care model and emphasized linkages with community re sources and multiagency coordination ( 25 , 26 , 28 ) . Key components included dementia care managers , formal procedures for communication within and between organizations and agencies , Internet-based care management , collaborative care planning with caregivers , caregiver self-management support , ongoing follow-up , and provider education . We hypothesized that patient and caregiver dyads in intervention clinics would receive care in higher accordance with guidelines ; receive more community re sources and services ; have fewer unmet caregiving assistance needs ; and have better patient and caregiver health and caregiving quality , social support , and perceived care quality than dyads receiving usual care . Methods The institutional review boards of the University of California , Los Angeles , and all participating health care organizations approved the study procedures . All enrolled patient and caregiver dyads provided written informed consent . Three health care organizations ( Kaiser Permanente San Diego , Scripps Clinic , University of California , San Diego , Healthcare ) and 3 community agencies ( Alzheimer 's AssociationSan Diego Chapter , Southern Caregiver Re source Center , Meals on WheelsGreater San Diego ) providing services for persons with dementia and their informal caregivers in the San Diego metropolitan area participated . Private group practice , academic group practice , and health maintenance organization practice types were represented by the 3 health care organizations . Study Participants The study included 18 clinics from the participating health care organizations ( 4 to 8 per organization ) ( Table 1 ) . The inclusion criterion was that these be primary care clinics . Table 1 . Characteristics of Participating Health Care Organizations * Patients with dementia who were age 65 years or older and receiving Medicare were identified by querying health care organization administrative data bases for occurrence during the previous year of a dementia diagnosis code ( 29 ) at an outpatient visit or hospitalization or a cholinesterase inhibitor prescription . Patient lists were grouped by primary provider and were circulated to those providers for confirmation of dementia diagnosis and identification of additional potential participants from his or her practice ( generating < 5 % of the sample ) . Patients had to have an informal caregiver ( age 18 years ) . Patients were recruited by mail with English- and Spanish- language letters from their physician and an opt-out postcard , followed by up to 3 mailings of a patient consent or assent form ( depending on the physician 's design ation of the patient 's ability to provide consent ) , a caregiver consent form ( containing a proxy consent for the patient if he or she was judged unable to provide consent ) , and a baseline caregiver survey . R and omization was conducted at the clinic level , based on the clinic-focused design of the care management intervention . Within each health care organization , we paired clinics by patient volume ; within each pair , we r and omly assigned 1 clinic to the intervention and the other clinic to usual care using a computerized r and om-number generator operated by a study statistician . Participants were unaware of clinic r and omization status at enrollment and at completion of the baseline survey and were not reminded of r and omization status at follow-up . Intervention A steering committee that included a physician from each health care organization , a leader from each community agency , a community caregiver , and investigators used a formal method ( 30 ) to identify 23 existing dementia guideline recommendations as care goals ( 11 , 12 , 14 ) . They also design ed a structured assessment , algorithms linking specific care management actions to assessment results , and interorganization care coordination and referral protocol s. A key intervention element was health care organization and community agencybased dementia care managers ( primarily social workers ) who received formal training and used an Internet-based care management software system for care planning and coordination ( 25 , 26 , 28 ) . Every enrolled patient and caregiver dyad in the intervention group was assigned 1 health care organization care manager , who contacted them to schedule a structured home assessment . Assessment responses were entered into the software system , generating a preliminary problem list and guides to care-plan actions . The care manager collaborated with the caregiver to prioritize problem areas ; teach problem-solving skills ; initiate care plan actions ; and send an assessment summary , a problem list , and selected recommendations to the patient 's primary care physician and other design ated providers . A menu of potential care plan actions ( for example , referral for respite care services ) was documented in a comprehensive care management manual . The care management protocol included ongoing follow-up , usually by telephone , with frequency based on need and a formal in-home re assessment every 6 months to assess the need for major care-plan revisions . The software system had a feature to enable efficient tracking of multiple cases and tasks . Referrals to a particular community agency were guided by flagged problem areas . With patient and caregiver consent , referrals were communicated through the software system to that agency , whose design ated care manager subsequently received system access to the assessment , problem list , and care plan . Each dyad could have 1 or more community agency care managers . Care managers from the health care organizations and community agencies received the same formal education and training program , which was conducted jointly , and met monthly to refine care coordination procedures . Care management began within a month after enrollment of the first dyads and was active throughout the study follow-up unless a case was closed , for example , because a patient moved out of the study area and no longer was enrolled in the health care organization . At each intervention clinic , more than 90 minutes of st and ardized , interactive seminars ( in up to 5 sessions ) on relevant care issues , including evaluation of acute behavioral changes , depression management , and determination of decision-making capacity ( 31 ) , were offered to primary care providers . Selected intervention tools and documents with more detailed descriptions can be accessed at www.adc.ucla.edu/access/access.swf . Patients , caregivers , and providers in the usual care group were not offered study interventions . Outcome Measures Primary Outcome The study 's primary outcome was OBJECTIVE To investigate General Practitioners ' ( GPs ) attitudes and practice s in relation to screening , diagnosing , and disclosing a dementia diagnosis to patients . DESIGN National postal survey . PARTICIPANTS A r and om sample of 600 GPs from a national data base of 2,400 . RESULTS Of the 600 GPs surveyed , 60 % returned question naires of which 50 % ( 300 ) were useable . GPs reported diagnosing on average four new cases of dementia annually . A multivariate analysis revealed that females diagnosed significantly fewer cases annually ( t=5.532 , df=289 , p<0.001 ) . A large majority of GPs reported performing thyroid function tests ( 77 % ) , B(12 ) ( 75 % ) and Folic acid tests ( 75 % ) to out rule reversible causes of cognitive impairment . The most reliable signs and symptoms of dementia identified were memory problems ( 58 % ) . Main barriers to diagnosis were difficulty differentiating normal ageing from symptoms of dementia ( 31 % ) , lack of confidence ( 30 % ) and the impact of the diagnosis on the patient ( 28 % ) . GPs ' age ( chi(2)=14.592 , df=3 , p<0.005 ) and gender ( chi(2)=11.436 , df=3 , p<0.01 ) were significantly associated with barriers to diagnosis . Only 19 % cl aim ed they often or always disclosed a diagnosis to a patient . Over one-third of GPs ( 38 % ) reported that the key factor influencing their disclosure patterns was their perceptions of the patient 's level of comprehension . Most GPs ( 90 % ) had never undergone any dementia specific training and most ( 83 % ) expressed a desire for this . CONCLUSIONS GPs experience difficulty diagnosing and disclosing a diagnosis of dementia to patients . To improve dementia care in Irel and , there is an urgent need to develop an active and more systematic approach to GP training in dementia care BACKGROUND AND OBJECTIVE In many industrialized countries diagnostic and therapeutic deficits in the management of patients with dementia are well documented . Due to demographic trends the next years will see a further rise in the number of affected patients . Accordingly , the knowledge and competence of the physicians taking care of these patients need to be keep up-to- date . In the context of the three-armed cluster-r and omized IDA trial ( IDA = " Initiative Demenzversorgung in der Allgemeinmedizin " ; Dementia Management Initiative in General Medicine ) , general practitioners ( GPs ) from the trial area ( Bavaria , Germany ) were trained in the diagnosis and treatment of dementia . METHODS The educational training concept was based on the evidence -based guideline of Witten/Herdecke University ( UWH ) . All participating GPs ( n = 137 , January 2006 ) received three hours training in the diagnosis of dementia . In addition , a subgroup was trained for two hours in dementia therapy ( n = 90 ) . Both groups obtained information about the study design . The didactic concept included screen and oral presentations by opinion leaders , video and interactive elements . At the beginning of the training sessions participants had to fill in a pilot-tested question naire with 20 multiple choice questions addressing the diagnosis and therapy of dementia ( pretest ) . The same question naire was completed at the end of the training session ( posttest ) complemented by an evaluation sheet . Overall and intergroup differences between pre- and post-test results ( increase in knowledge ) were compared using the Chi-Square test . RESULTS Overall , the quality of the training received a positive rating by the participants . By the end of January 2006 , 137 doctors had been trained . The mean knowledge gain was 4.0 + 2.6 correctly answered questions ( p<0.001 ; Cl 3.6 to 4.5 ) comparing pre- and posttest ( n = 132 ) . In the group trained on diagnosis alone ( n = 45 ) , the gain averaged 2.0+/-1.9 questions . The group with additional training on therapy ( n = 87 ) achieved a difference of 5.1 -2.3 questions ( p<0.001 ) . DISCUSSION Participants of the dementia training achieved a substantial gain of knowledge . The extent of this knowledge increase was associated with the attendance to respective training modules . An ongoing trial will add further information about knowledge translation in the field of dementia OBJECTIVES To evaluate the effect of a multicomponent dementia care management program on primary care provider knowledge , attitudes , and perceptions of quality of dementia care . DESIGN A clinic-level r and omized , controlled trial of a comprehensive care management program for patients with dementia and their nonprofessional caregivers . The program included provider education and protocol s for care managers to communicate with patients ' medical providers . SETTING Eighteen clinics ( nine intervention , nine [ corrected ] usual care ) in three healthcare systems in San Diego , California . PARTICIPANTS Two hundred thirty-two medical providers ; 129 from nine [ corrected ] intervention clinics ; 103 from nine [ corrected ] usual-care clinics . MEASUREMENTS Providers were surveyed 9 months after intervention onset on knowledge ( five items on four topics ) , attitudes about dementia ( three items ) , and perception of quality of dementia care in their practice setting ( three items ) . Multivariable linear and logistic regression models were used to evaluate the differences between intervention and usual-care providers , adjusting for covariate effects across groups and clustering by clinic . RESULTS One hundred sixty-six of 232 ( 72 % ) providers responded . Intervention providers had better knowledge about assessing decision-making capacity than usual-care providers ( adjusted difference in percentage correct = 12 % ; adjusted odds ratio = 2.4 , 95 % confidence interval = 1.2 - 4.8 ) . Intervention providers viewed dementia patients as more difficult to manage in primary care than usual-care providers ( P = .03 ) . There were no other differences in knowledge , attitudes , or care quality perceptions across intervention and usual-care providers . CONCLUSION A comprehensive dementia care management model result ed in few differences in provider knowledge or attitudes favorable to dementia care , suggesting that this care model 's effects on quality were primarily mediated through other components of the care management program OBJECTIVE To measure general practitioners ' knowledge of , confidence with and attitudes to the diagnosis and management of dementia in primary care . SETTING 20 general practice s of varying size and prior research experience in Central Scotl and , and 16 similarly varied practice s in north London . PARTICIPANTS 127 general practitioners who had volunteered to join a r and omised controlled trial of educational interventions about dementia diagnosis and management . METHODS Self-completion question naires covering knowledge , confidence and attitudes were retrieved from practitioners prior to the educational interventions . RESULTS General practitioners ' knowledge of dementia diagnosis and management is good , but poor awareness of its epidemiology leads to an over-estimate of caseload . Knowledge of local diagnostic and support services is less good , and one third of general practitioners expressed limited confidence in their diagnostic skills , whilst two-thirds lacked confidence in management of behaviour and other problems in dementia . The main difficulties identified by general practitioners were talking with patients about the diagnosis , responding to behaviour problems and coordinating support services . General practitioners perceived lack of time and lack of social services support as the major obstacles to good quality care more often than they identified their own unfamiliarity with current management or with local re sources . Attitudes to the disclosure of the diagnosis , and to the potential for improving the quality of life of patients and carers varied , but a third of general practitioners believed that dementia care is within a specialist 's domain , not that of general practice . More experienced and male general practitioners were more pessimistic about dementia care , as were general practitioners with lower knowledge about dementia . Those reporting greater difficulty with dementia diagnosis and management and those with lower knowledge scores were also less likely to express attitudes endorsing open communication with patient and carer . CONCLUSION Educational support for general practitioners should concentrate on epidemiological knowledge , disclosure of the diagnosis and management of behaviour problems in dementia . The availability and profile of support services , particularly social care , need to be enhanced , if earlier diagnosis is to be pursued as a policy objective in primary care |
11,140 | 24,664,414 | In three of these studies , simulation-enhanced CRM training was found significantly more effective than no intervention or didactic teaching .
Conclusions Based on a small number of studies , this systematic review found that CRM skills learned at the simulation centre are transferred to clinical setting s , and the acquired CRM skills may translate to improved patient outcomes , including a decrease in mortality .
Dans trois de ces études , la formation à la CRM soutenue par des simulations s’est avérée significativement plus efficace que l’absence d’intervention ou un enseignement didactique .
Conclusions Reposant sur un petit nombre d’études , cette analyse systématique a trouvé que les habiletés en matière de CRM apprises au centre de simulations sont transférées dans des cadres cliniques et que les habiletés acquises de CRM peuvent se traduire par une amélioration de l’évolution , y compris une baisse de la mortalité | Purpose Simulation-based learning is increasingly used by healthcare professionals as a safe method to learn and practice non-technical skills , such as communication and leadership , required for effective crisis re source management ( CRM ) .
This systematic review was conducted to gain a better underst and ing of the impact of simulation-based CRM teaching on transfer of learning to the workplace and subsequent changes in patient outcomes .
RésuméObjectifL’apprentissage basé sur des simulations est de plus en plus utilisé par les professionnels de santé comme méthodes sécuritaires d’apprentissage et de pratique de compétences non techniques , comme la communication et le leadership , qui sont nécessaires pour une gestion efficace des res sources en situation de crise ( CRM ) .
Cette étude systématique a été menée pour mieux comprendre l’impact de l’enseignement à partir de simulations de la CRM sur le transfert des connaissances sur le lieu de travail et les changements ultérieurs sur l’évolution des patients . | Objective : To evaluate the viability and effectiveness of a simulation-based pediatric mock code program on patient outcomes , as well as residents ' confidence in performing resuscitations . A resident 's leadership ability is integral to accurate and efficient clinical response in the successful management of cardiopulmonary arrest ( CPA ) . Direct experience is a contributing factor to a resident 's code team leadership ability ; however , opportunities to gain experience are limited by relative infrequency of pediatric arrests and code occurrences when residents are on service . Design : Longitudinal , mixed- methods research design . Setting : Children 's hospital at an tertiary care academic medical center . Patients : Pediatric . Interventions : Clinicians responsible for pediatric resuscitations responded to mock codes r and omly called at increasing rates over a 48-month period , just as they would an actual CPA event . Events were recorded and used for immediate debriefing facilitated by clinical faculty to provide residents feedback about their performance . Measurements : Self- assessment data were collected from all team members . Hospital records for pediatric CPA survival rates were examined for the study duration . Results : Survival rates increased to approximately 50 % ( p = .000 ) , correlating with the increased number of mock codes ( r = .87 ) . These results are significantly above the average national pediatric CPA survival rates and held steady for 3 consecutive years , demonstrating the stability of the program 's outcomes . Conclusions : This study suggests that a simulation-based mock code program may significantly benefit pediatric patient CPA outcomes —applied clinical outcomes —not simply learner perceived value , increased confidence , or simulation-based outcomes . The use of mock codes as an integral part of residency programs could provide residents with the resuscitation training they require to become proficient in their practice . Future programs that incorporate transport scenarios , ambulatory care , and other outpatient setting s could further benefit pediatric patients in prehospital context Objective : To determine if high fidelity simulation based team training can improve clinical team performance when added to an existing didactic teamwork curriculum . Setting : Level 1 trauma center and academic emergency medicine training program . Participants : Emergency department ( ED ) staff including nurses , technicians , emergency medicine residents , and attending physicians . Intervention : : ED staff who had recently received didactic training in the Emergency Team Coordination Course ( ETCC ® ) also received an 8 hour intensive experience in an ED simulator in which three scenarios of graduated difficulty were encountered . A comparison group , also ETCC trained , was assigned to work together in the ED for one 8 hour shift . Experimental and comparison teams were observed in the ED before and after the intervention . Design : Single , crossover , prospect i ve , blinded and controlled observational study . Teamwork ratings using previously vali date d behaviorally anchored rating scales ( BARS ) were completed by outside trained observers in the ED . Observers were blinded to the identification of the teams . Results : There were no significant differences between experimental and comparison groups at baseline . The experimental team showed a trend towards improvement in the quality of team behavior ( p = 0.07 ) ; the comparison group showed no change in team behavior during the two observation periods ( p = 0.55 ) . Members of the experimental team rated simulation based training as a useful educational method . Conclusion : High fidelity medical simulation appears to be a promising method for enhancing didactic teamwork training . This approach , using a number of patients , is more representative of clinical care and is therefore the proper paradigm in which to perform teamwork training . It is , however , unclear how much simulator based training must augment didactic teamwork training for clinical ly meaningful differences to become apparent OBJECTIVE Evaluate the impact of a team training curriculum for residents and multidisciplinary trauma team members on team communication , coordination and clinical efficacy of trauma resuscitation . DESIGN Prospect i ve , cohort intervention comparing pre- vs. post-training performance . The intervention was a human patient simulator (HPS)-based , in situ team training curriculum , comprising a one-hour web based didactic followed by HPS training in the emergency department ( ED ) . Teams were trained in multidisciplinary groups of 5 - 8 persons . Each HPS session included three fifteen minute scenarios with immediate video-enabled debriefing . Structured debriefing and teamwork assessment was performed with a modified NOTECHS scale for trauma ( T-NOTECHS ) . Teams were assessed for performance changes during HPS-based training , as well as in actual trauma resuscitations . SETTING The Queen 's Trauma Center ( Level II ) ; the primary teaching hospital for the University of Hawaii Surgical Residency . PARTICIPANTS 137 multidisciplinary trauma team members , including residents ( n = 24 ) , ED and trauma attending physicians , nurses , respiratory therapists , and ED technicians . RESULTS During HPS-based training sessions , significant improvements in teamwork ratings , and in clinical task speed and completion rates were noted between the first and the last scenario.244 real-life blunt trauma resuscitations were observed for six months before and after training . There was a significant improvement in mean teamwork scores from the pre-to post-training resuscitations . Moreover , there were significant improvements in the objective parameters of speed and completeness of resuscitation . This was manifest by a 76 % increase in the frequency of near-perfect task completion ( ≤ 1 unreported task ) , and a reduction in the mean overall ED resuscitation time by 16 % . CONCLUSIONS A relatively brief ( four-hour ) HPS-based curriculum can improve the teamwork and clinical performance of multidisciplinary trauma teams that include surgical residents . This improvement was evidence d both in simulated and actual trauma setting s , and across teams of varying composition . HPS-based trauma teamwork training appears to be an educational method that can impact patient care Problem : Advance cardiac life support ( ACLS ) training does not address coordination of team re sources to improve the ability of teams to deliver needed treatments reliably and rapidly . Our objective was to use a human simulation training educational environment to develop multidisciplinary team skills and improve medical emergency team ( MET ) performance . We report findings of a crisis team training course that is focused on organization . Setting : Large center for human simulation training at a university affiliated tertiary care hospital . Participants : Ten courses were delivered and 138 clinical ly experienced individuals were trained ( 69 critical care nurses , 48 physicians , and 21 respiratory therapists ) . All participants were ACLS trained and experienced in responding to cardiac arrest situations . Course design : Each course had four components : ( 1 ) a web based presentation and pretest before the course ; ( 2 ) a brief reinforcing didactic session on the day of the course ; ( 3 ) three of five different simulated scenarios ; each followed by ( 4 ) debriefing and analysis with the team . Three of five simulator scenarios were used ; scenario selection and order was r and om . Trainees did not repeat any scenario or role during the training . Participants were video recorded to assist debriefing . Debriefing focused on reinforcing organizational aspects of team performance : assuming design ated roles independently , completing goals ( tasks ) assigned to each role , and directed communication . Measures for improvement : Participants grade d their performance of specific organizational and treatment tasks within specified time intervals by consensus . Simulator “ survival ” depended on supporting oxygenation , ventilation , circulation within 60 seconds , and delivering the definitive treatment within 3 minutes . Effects of change : Simulated survival ( following predetermined criteria for death ) increased from 0 % to 89 % . The initial team task completion rate was 10–45 % and rose to 80–95 % during the third session . Lessons learnt : Training multidisciplinary teams to organize using simulation technology is feasible . This preliminary report warrants more detailed inquiry Background : Simulation-based training is useful in improving physicians ' skills . However , no r and omized controlled trials have been able to demonstrate the effects of simulation teaching in real-life patient care . This study aim ed to determine whether simulation-based training or an interactive seminar result ed in better patient care during weaning from cardiopulmonary bypass (CPB)—a high stakes clinical setting . Methods : This study was conducted as a prospect i ve , single-blinded , r and omized controlled trial . After institutional research board approval , 20 anesthesiology trainees , postgraduate year 4 or higher , inexperienced in CPB weaning , and 60 patients scheduled for elective coronary artery bypass grafting were recruited . Each trainee received a teaching syllabus for CPB weaning 1 week before attempting to wean a patient from CPB ( pretest ) . One week later , each trainee received a 2-h training session with either high-fidelity simulation-based training or a 2-h interactive seminar . Each trainee then weaned patients from CPB within 2 weeks ( posttest ) and 5 weeks ( retention test ) from the intervention . Clinical performance was measured using the vali date d Anesthesiologists ' Nontechnical Skills Global Rating Scale and a checklist of expected clinical actions . Results : Pretest Global Rating Scale and checklist performances were similar . The simulation group scored significantly higher than the seminar group at both posttest ( Global Rating Scale [ mean ± st and ard error ] : 14.3 ± 0.41 vs. 11.8 ± 0.41 , P < 0.001 ; checklist : 89.9 ± 3.0 % vs. 75.4 ± 3.0 % , P = 0.003 ) and retention test ( Global Rating Scale : 14.1 ± 0.41 vs. 11.7 ± 0.41 , P < 0.001 ; checklist : 93.2 ± 2.4 % vs. 77.0 ± 2.4 % , P < 0.001 ) . Conclusion : Skills required to wean a patient from CPB can be acquired through simulation-based training . Compared with traditional interactive seminars , simulation-based training leads to improved performance in patient care by senior trainees in anesthesiology Background : The debriefing process during simulation-based education has been poorly studied despite its educational importance . Videotape feedback is an adjunct that may enhance the impact of the debriefing and in turn maximize learning . The purpose of this study was to investigate the value of the debriefing process during simulation and to compare the educational efficacy of two types of feedback , oral feedback and videotape-assisted oral feedback , against control ( no debriefing ) . Methods : Forty-two anesthesia residents were enrolled in the study . After completing a pretest scenario , participants were r and omly assigned to receive no debriefing , oral feedback , or videotape-assisted oral feedback . The debriefing focused on nontechnical skills performance guided by crisis re source management principles . Participants were then required to manage a posttest scenario . The videotapes of all performances were later review ed by two blinded independent assessors who rated participants ' nontechnical skills using a vali date d scoring system . Results : Participants ' nontechnical skills did not improve in the control group , whereas the provision of oral feedback , either assisted or not assisted with videotape review , result ed in significant improvement ( P < 0.005 ) . There was no difference in improvement between oral and video-assisted oral feedback groups . Conclusions : Exposure to a simulated crisis without constructive debriefing by instructors offers little benefit to trainees . The addition of video review did not offer any advantage over oral feedback alone . Valuable simulation training can therefore be achieved even when video technology is not available Background and objective Fibreoptic intubation is an essential skill in anaesthesiology that is challenging to learn in the clinical setting . The goal of this study was to evaluate ‘ virtual fibreoptic intubation ’ ( VFI ) software as an adjunct to the traditional fibreoptic intubation teaching . Methods After informed consent , 42 undergraduate medical students were r and omized into two groups . The ‘ control group ’ was taught conventionally by an expert bronchoscopist with a 1 h lecture . In addition to the didactic lecture by the expert , the ‘ VFI group ’ was given the VFI CD-ROM , and students self-trained with the software until they felt competent performing a virtual fibreoptic bronchoscopy on the normal patient models . Students were evaluated 2 weeks later on their first orotracheal fibreoptic intubation of an airway manikin . The primary endpoint was success , as evaluated by a staff anaesthesiologist blinded to the group of teaching . Fibreoptic intubation ability was the secondary endpoint . Results The fibreoptic intubation success rate was significantly higher in the VFI group than in the control group ( 81 versus 52 % , P < 0.05 ) . Among 10 failures in the control group , nine were due to oesophageal intubation as compared with only one out of four in the VFI group . Among four failures in the VFI group , three were because of taking longer than 4 min as compared with only one out of 10 in the control group . The VFI group tended towards better ability in the procedural skills of fibreoptic intubation than the control group . Conclusion Self-training in fibreoptic intubation with the VFI software may improve the acquisition of fibreoptic intubation skills Objective : To compare the effectiveness of an interprofessional within-team debriefing with that of an instructor-led debriefing on team performance during a simulated crisis . Background : Although instructor-led simulation debriefing is considered the “ gold st and ard ” in team-based simulation education , cost and logistics are limiting factors for its implementation . Within-team debriefing , led by the individuals of the team itself rather than an external instructor , has the potential to address these limitations . Methods : One hundred twenty subjects were grouped into 40 operating room teams consisting of 1 anesthesia trainee , 1 surgical trainee , and 1 staff circulating operating room nurse . All teams managed a simulated crisis scenario ( pretest ) . Teams were then r and omized to either a within-team debriefing group or an instructor-led debriefing group . In the within-team debriefing group , the teams review ed the video of their scenario by themselves . The teams in the instructor-led debriefing group review ed their scenario guided by a trained instructor . Immediately after debriefing , all teams managed a different intraoperative crisis scenario ( posttest ) . All sessions were videotaped . Blinded expert examiners used the vali date d Team Emergency Assessment Measure scale to assess crisis re source management performance of all teams in r and om order . Result : Team performance significantly improved from pretest to posttest ( P = 0.008 ) regardless of the type of debriefing . There was no significant difference in the degree of improvement between within-team debriefing and instructor-led debriefing ( P = 0.52 ) . Conclusions : Within-team debriefing results in measurable improvements in team performance in simulated crisis scenarios . This form of debriefing may be as effective as instructor-led team debriefing , which could improve re source utilization and feasibility of team-based simulation ( NCT01067378 ) Objective : To examine the effectiveness of self-debriefing as compared to instructor debriefing in the change of nontechnical skills performance of anesthesiology residents . Design : Prospect i ve , r and omized , controlled study . Setting : A university hospital simulation center . Subjects : Fifty anesthesiology residents . Interventions : Subjects were instructed in the principles of nontechnical skills for crisis management . Subsequently , each resident participated in a high-fidelity simulated anesthesia crisis scenario ( pretest ) . Participants were r and omized to either a video-assisted self-debriefing or instructor debriefing . In the self-debriefing group , subjects review ed their pretest scenario by themselves , guided by the Anesthetists ' Non-Technical Skills scale . The instructor debriefing group review ed their pretest scenario guided by an expert instructor also using the Anesthetists ' Non-Technical Skills scale as a framework . Immediately following their respective debriefings , subjects managed a second simulated crisis ( post-test ) . Measurements and Main Results : After all data were collected , two blinded experts independently rated videos of all performances in a r and om order using the Anesthetists ' Non-Technical Skills scale . Performance significantly improved from pretest to post-test ( p < .01 ) regardless of the type of debriefing received . There was no significant difference in the degree of improvement between self-debriefing and instructor debriefing ( p = .58 ) . Conclusions : Nontechnical skills for crisis re source management improved with training , as measured by the Anesthetists ' Non-Technical Skills scale . Crisis re source management can be taught , with measurable improvements . Effective teaching of nontechnical skills can be achieved through formative self- assessment even when instructors are not available BACKGROUND Birth trauma is a low-frequency , high-severity event , making obstetrics a major challenge for patient safety . Yet , few strategies have been shown to eliminate preventable perinatal harm . Interdisciplinary team training was prospect ively evaluated to assess the relative impact of two different learning modalities to improve nontechnical skills (NTS)--the cognitive and interpersonal skills , such as communication and teamwork , that supplement clinical and technical skills and are necessary to ensure safe patient care . METHODS Between 2005 and 2008 , perinatal morbidity and mortality data were prospect ively collected using the Weighted Adverse Outcomes Score ( WAOS ) and a culture of safety survey ( Safety Attitudes Question naire ) at three small-sized community hospitals . In a small cluster r and omized clinical trial conducted in the third quarter of 2007 , one of the hospitals served as a control group and two served as the treatment intervention sites -- one hospital received the TeamSTEPPS didactic training program and one hospital received both the TeamSTEPPS program along with a series of in-situ simulation training exercises . RESULTS A statistically significant and persistent improvement of 37 % in perinatal morbidity was observed between the pre- and postintervention for the hospital exposed to the simulation program . There were no statistically significant differences in the didactic-only or the control hospitals . Baseline perceptions of culture of safety were high at all three hospitals , and there were no significant changes . CONCLUSIONS A comprehensive interdisciplinary team training program using in-situ simulation can improve perinatal safety in the hospital setting . This is the first evidence providing a clear association between simulation training and improved patient outcomes . Didactics alone were not effective in improving perinatal outcomes BACKGROUND : Training surgical residents to manage critically injured patients in a timely fashion presents a significant challenge . Simulation may have a role in this educational process , but only if it can be demonstrated that skills learned in a simulated environment translate into enhanced performance in real-life trauma situations . METHODS : A five-part , scenario-based trauma curriculum was developed specifically for this study . Midlevel surgical residents were r and omized to receiving this curriculum in didactic lecture ( LEC ) fashion or with the use of a human performance simulator ( HPS ) . A written learning objectives test was administered at the completion of the training . The first four major trauma resuscitations performed by each participating resident were captured on videotape in the emergency department and grade d by two experienced judges blinded to the method of training . The assessment tool used by the judges included an evaluation of both initial trauma evaluation or treatment skills ( part I ) and crisis management skills ( part II ) as well as an overall score ( poor/fail , adequate , or excellent ) . RESULTS : The two groups of residents received almost identical scores on the posttraining written test . Average SIM and LEC scores for part I were also similar between the two groups . However , SIM-trained residents received higher overall scores and higher scores for part II crisis management skills compared with the LEC group , which was most evident in the scores received for the teamwork category ( p = 0.04 ) . CONCLUSIONS : A trauma curriculum incorporating simulation shows promise in developing crisis management skills that are essential for evaluation of critically injured patients BACKGROUND The Olympus colonoscopy simulator provides a high-fidelity training platform design ed to develop knowledge and skills in colonoscopy . It has the potential to shorten the learning process to competency . OBJECTIVE To investigate the efficacy of the simulator in training novices in colonoscopy by comparing training outcomes from simulator training with those of st and ard patient-based training . DESIGN Multinational , multicenter , single-blind , r and omized , controlled trial . SETTING Four academic endoscopy centers in the United Kingdom , Italy , and The Netherl and s. PARTICIPANTS AND INTERVENTION This study included 36 novice colonoscopists who were r and omized to 16 hours of simulator training ( subjects ) or patient-based training ( controls ) . Participants completed 3 simulator cases before and after training . Three live cases were assessed after training by blinded experts . MAIN OUTCOME MEASUREMENTS Automatically recorded performance metrics for the simulator cases and blinded expert assessment of live cases using Direct Observation of Procedural Skills and Global Score sheets . RESULTS Simulator training significantly improved performance on simulated cases compared with patient-based training . Subjects had higher completion rates ( P=.001 ) and shorter completion times ( P < .001 ) and demonstrated superior technical skill ( reduced simulated pain scores , correct use of abdominal pressure , and loop management ) . On live colonoscopy , there were no significant differences between the 2 groups . LIMITATIONS Assessment tools for live colonoscopies may lack sensitivity to discriminate between the skills of relative novices . CONCLUSION Performance of novices trained on the colonoscopy simulator matched the performance of those with st and ard patient-based colonoscopy training , and novices in the simulator group demonstrated superior technical skills on simulated cases . The simulator should be considered as a tool for developing knowledge and skills prior to clinical practice |
11,141 | 25,908,932 | Conclusion Immigrants ’ countries of origin and host countries have reached different stages of the ‘ smoking epidemic ’ where , in addition , smoking among women lags behind that in men .
Immigrants might ‘ move ’ between the stages as ( I ) the ( non-western ) countries of origin tend to be in the early phase , ( II ) the ( western ) host countries more in the advanced phase of the epidemic and ( III ) the arrival in the host countries initiates the acculturation process .
This could explain the ‘ imported ’ high (men)/low ( women ) prevalence among less acculturated immigrants .
The low (men)/high ( women ) prevalence among more acculturated immigrants indicates an adaptation towards the social norms of the host countries with ongoing acculturation | Introduction We aim ed to identify factors associated with smoking among immigrants .
In particular , we investigated the relationship between acculturation and smoking , taking into consideration the stage of the ‘ smoking epidemic ’ in the countries of origin and host countries of the immigrants . | OBJECTIVES To measure the prevalence and patterns of , and risk factors for , smoking and other tobacco use among Vietnamese men in Massachusetts ( United States ) . METHODS Data were obtained via a telephone interview of 774 Vietnamese men in 1994 . DESIGN Cross-sectional survey administered via telephone in 1994 . SETTING Massachusetts , United States . SUBJECTS R and omly selected Vietnamese men ( n = 774 ) . MAIN OUTCOME MEASURES Present and past use of tobacco products , knowledge and attitudes regarding tobacco , and risk factors for tobacco use . Results were compared with data from the Massachusetts general population . RESULTS Vietnamese men smoked at a rate 1.9 times that of the Massachusetts general men ’s rate ( 43 % vs24 % ) . The smoking rate did not decrease with increasing length of residence in the United States . In a logistic regression , risk factors for current smoking were : age in the thirties ; history of parental smoking ; lower educational level ; higher depression score ; low level of exercise ; lack of health insurance ; and geographical origin from the south coast of Vietnam . Smoking cessation declined with increasing depression score . Most smokers ( 76 % ) had no plans to quit smoking . CONCLUSIONS Vietnamese men smoke at much higher rates than the general population , and are much less likely to be planning cessation . High rates of depression and sociocultural barriers to smoking cessation must be addressed in efforts to reduce tobacco use among this high-risk population 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 Vietnamese population s in Vietnam and the United States have a high prevalence of smoking . The associations among behavioral risk factors , acculturation , and smoking among the Vietnamese population living in the United States are not well documented . The present study aim ed to identify the factors associated with smoking behavior among Vietnamese men living in Santa Clara County , California . A cross-sectional r and om-digit-dialed telephone survey was conducted . The sampling frame consisted of 27 Vietnamese surnames from the Santa Clara County telephone directory . A total of 660 adult respondents were interviewed to collect information on general health status , alcohol and tobacco use , HIV/AIDS , sexual behavior , injury control , hypertension , cholesterol screening , and acculturation . Of the 660 adults interviewed , 364 ( 55.2 % ) were male and 296 ( 44.8 % ) were female . Among males , 31.9 % were current smokers , and among females , only one woman reported smoking . Univariate analyses revealed that having less than a college education , having poor English language skills , using Vietnamese at home and with friends , being less acculturated , not having a routine physical or blood cholesterol check , and being a binge drinker were significantly associated with an increased likelihood of smoking . Multivariate analysis revealed two independently associated factors : Respondents who were more acculturated were less likely to smoke ( OR = 0.38 , 95 % CI = 0.18 - 0.83 ) , and those not having cholesterol checked were more likely to smoke ( OR = 2.48 , 95 % CI = 1.30 - 4.71 ) . Acculturation level was inversely associated with smoking among Vietnamese adult men in Santa Clara County . Other health risk behaviors coexisted with smoking behavior and should be considered in prevention programs CONTEXT In recent decades , there has been a rapid and substantial increase in tobacco consumption in China , particularly by men , but little is known from local epidemiologic studies about the pattern of smoking-related deaths . OBJECTIVE To assess the current health effects of cigarette smoking in Shanghai , China . DESIGN Prospect i ve observational study of mortality in relation to cigarette smoking . SETTING Eleven factories in urban Shanghai . SUBJECTS A total of 9351 adults ( 6494 men and 2857 women ) aged 35 to 64 years at baseline survey during the 1970s . OUTCOME MEASURES All-cause and cause-specific mortality . RESULTS During an average follow-up of 16 years , 881 men and 207 women died . Among men , 61 % had described themselves as current cigarette smokers at baseline , and their overall mortality was significantly greater than that of nonsmokers ( relative risk [ RR ] , 1.4 ; 95 % confidence interval [ CI ] , 1.2 - 1.7 ; P<.001 ) . The excess was almost twice as great ( RR , 1.8 ; 95 % CI , 1.5 - 2.2 [ corrected ] ; P<.001 ) among the men who had begun smoking before the age of 25 years and was significantly associated with the number of cigarettes smoked ( P<.001 for trend ) after adjustment for other major risk factors . The chief sources of the excess were lung cancer ( RR , 3.8 ; 95 % CI , 2.1 - 6.8 ; P<.001 ) , esophageal cancer ( RR , 3.6 ; 95 % CI , 1.2 - 10.5 ; P=.02 ) , liver cancer ( RR , 2.0 ; 95 % CI , 1.1 - 3.7 ; P=.03 ) , coronary heart disease ( RR , 1.8 ; 95 % CI , 1.0 - 3.2 ; P=.04 ) , and chronic obstructive pulmonary disease ( RR , 2.5 ; 95 % CI , 1.4 - 4.4 ; P<.01 ) . Among the men in this Chinese population , about 20 % ( 95 % CI , 12%-29 % ) of all deaths during the study period could be attributed to cigarette smoking . Of these deaths , one third involved lung cancer , one third involved other cancers , and one third involved other diseases . Only 7 % of women described themselves as current cigarette smokers at baseline , but among them there was also a statistically significant excess of overall mortality ( RR , 1.7 ; 95 % CI , 1.2 - 2.5 ; P<.01 ) . CONCLUSIONS Cigarette smoking is already a major cause of death in China , and among middle-aged Shanghai men , about 20 % of all deaths during the 1980s were due to smoking . The excess was greatest among men who began smoking before the age of 25 years , about 47 % of whom would , at 1987 mortality rates , die between the ages of 35 and 69 years ( compared with only 29 % of nonsmokers ) . These estimates reflect the consequences of past smoking patterns . The future health effects of current smoking patterns are likely to be greater because of the recent large increase in cigarette consumption , particularly at younger ages , in China This study presents population estimates of cigarette use among adults of Korean descent residing in California . Data were drawn from telephone interviews with adults ( N=2,830 ) developed from a r and om sampling of listed persons in California with Korean surnames . A total of 86 % of attempted interviews were completed , and 85 % of the interviews were conducted in Korean . Less acculturated men and more acculturated women reported higher present and predicted future rates of smoking after multivariate statistical controls were applied . Sharply divergent rates of cigarette use were found between the genders . Although men did not smoke their first cigarette or smoke cigarettes regularly earlier than women , both groups began smoking later than adults born in the United States . To be effective , tobacco intervention efforts must be tailored specifically to cultures of each minority . Results suggest that acculturation processes influence tobacco use differentially by gender , and future research is needed to identify the implication s of processes in tobacco initiation and cessation Background This study examined two main hypotheses : a ) Polish immigrants ' smoking estimates are greater than their Irish counterparts ( b ) Polish immigrants purchasing cigarettes from Pol and smoke " heavier " ( ≥ 20 cigarettes a day ) when compared to those purchasing cigarettes from Irel and . The study also set out to identify significant predictors of ' current ' smoking ( some days and everyday ) among the Polish immigrants . Methods Dublin residents of Polish origin ( n = 1,545 ) completed a previously vali date d Polish question naire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends ( July – August , 2007 ) . The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period ( n = 484 ) . Results Age-sex adjusted smoking estimates were : 47.6 % ( 95 % Confidence Interval [ CI ] : 47.3 % ; 48.0 % ) among the Poles and 27.8 % ( 95 % CI : 27.2 % ; 28.4 % ) among the general Irish population ( p < 0.001 ) . Of the57 % of smokers ( n = 345/606 ) who purchased cigarettes solely from Pol and and the 33 % ( n = 198/606 ) who purchased only from Irel and , 42.6 % ( n = 147/345 ) and 41.4 % ( n = 82/198 ) were " heavy " smokers , respectively ( p = 0.79 ) . Employment ( Odds Ratio [ OR ] : 2.89 ; 95 % CI : 1.25–6.69 ) , lower education ( OR : 3.76 ; 95%CI : 2.46–5.74 ) , and a longer stay in Irel and ( > 24 months ) were significant predictors of current smoking among the Poles . An objective validation of the self-reported smoking history of a r and omly selected sub- sample immigrant group , using expired carbon monoxide ( CO ) measurements , showed a highly significant correlation coefficient ( r = 0.64 ) of expired CO levels with the reported number of cigarettes consumed ( p < 0.0001 ) . Conclusion Polish immigrants ' smoking estimates are higher than their Irish counterparts , and particularly if employed , with only primary -level education , and are overseas > 2 years OBJECTIVE The Operant Model of Acculturation predicts that health behaviors that have a low prevalence ( < 20 % ) among Traditional ( low-acculturated ) minorities increase in prevalence with acculturation and hence have a higher prevalence among their Acculturated counterparts . Alternatively , health behaviors that have a high prevalence ( > 45 % ) among Traditional minorities decrease with acculturation and thereby have a lower prevalence among their acculturated cohorts . The purpose of this study was to test this model for the first time . DESIGN Data on the 7,249 Mexican American adults in the 2001 California Health Interview Survey ( CHIS ) , a statewide , r and om-digit-dial telephone survey , were used . MAIN OUTCOME MEASURES Two proxies for acculturation ( nativity , language spoken at home ) were predictors in analyses of cigarette smoking , exercise , and 5 + daily fruit/vegetable consumption . RESULTS For all three health behaviors , results were fully supportive of the Operant Model irrespective of acculturation-proxy and demographic variables . CONCLUSION The Operant Model may provide a coherent framework for predicting and underst and ing the role of acculturation in ethnic minority health behavior . Findings are discussed in terms of tailoring and targeting interventions in a manner consistent with the acculturation-related changes in health behavior that are likely to occur |
11,142 | 17,132,118 | Strengthening interventions increase strength , improve activity , and do not increase spasticity .
These findings suggest that strengthening programs should be part of rehabilitation after stroke | QUESTION Is strength training after stroke effective ( ie , does it increase strength ) , is it harmful ( ie , does it increase spasticity ) , and is it worthwhile ( ie , does it improve activity ) ? | BACKGROUND AND PURPOSE It has been suggested that cyclic neuromuscular electrical stimulation ( ES ) may enhance motor recovery after stroke . We have investigated the effects of ES of the wrist extensors on impairment of wrist function and on upper-limb disability in patients being rehabilitated after acute stroke . METHODS We recruited 60 hemiparetic patients ( mean age , 68 years ) 2 to 4 weeks after stroke into a r and omized , controlled , parallel-group study comparing st and ard rehabilitation treatment with st and ard treatment plus ES of wrist extensors ( 3 times 30 minutes daily for 8 weeks ) . Isometric strength of wrist extensors was measured using a device built for that purpose . Upper-limb disability was assessed with use of the Action Research Arm Test ( ARAT ) . Observations were continued for 32 weeks ( 24 weeks after the finish of ES or the control intervention phase ) . RESULTS The change in isometric strength of wrist extensors ( at an angle of 0 degrees extension ) was significantly greater in the ES group than the control group at both 8 and 32 weeks ( P=0.004 , P=0.014 by Mann Whitney U test ) . At week 8 the grasp and grip subscores of the ARAT increased significantly in the ES group compared with that in the control group ( P=0.013 and P=0.02 , respectively ) ; a similar trend was seen for the total ARAT score ( P=0.11 ) . In the subgroup of 33 patients with some residual wrist extensor strength at study entry ( moment at 0 degrees extension > 0 ) , the ARAT total score had increased at week 8 by a mean of 21.1 ( SD , 12.7 ) in the ES group compared with 10.3 ( SD , 9.0 ) in the control group ( P=0.024 , Mann Whitney U test ) ; however , at 32 weeks the differences between these 2 subgroups were no longer statistically significant . CONCLUSIONS ES of the wrist extensors enhances the recovery of isometric wrist extensor strength in hemiparetic stroke patients . Upper-limb disability was reduced after 8 weeks of ES therapy , with benefits most apparent in those with some residual motor function at the wrist . However , it is not clear how long the improvements in upper-limb disability are maintained after ES is discontinued BACKGROUND AND PURPOSE Rehabilitation care after stroke is highly variable and increasingly shorter in duration . The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear . The objective of this study was to determine whether a structured , progressive , physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care . METHODS This r and omized , controlled , single-blind clinical trial was conducted in a metropolitan area and 17 participating healthcare institutions . We included persons with stroke who were living in the community . One hundred patients ( mean age , 70 years ; mean Orpington score , 3.4 ) consented and were r and omized from a screened sample of 582 . Ninety-two subjects completed the trial . Intervention was a structured , progressive , physiologically based , therapist-supervised , in-home program of thirty-six 90-minute sessions over 12 weeks targeting flexibility , strength , balance , endurance , and upper-extremity function . Main outcome measures were postintervention strength ( ankle and knee isometric peak torque , grip strength ) , upper- and lower-extremity motor control ( Fugl Meyer ) , balance ( Berg and functional reach ) , endurance ( peak aerobic capacity and exercise duration ) , upper-extremity function ( Wolf Motor Function Test ) , and mobility ( timed 10-m walk and 6-minute walk distance ) . RESULTS In the intention-to-treat multivariate analysis of variance testing the overall effect , the intervention produced greater gains than usual care ( Wilk 's lambda=0.64 , P=0.0056 ) . Both intervention and usual care groups improved in strength , balance , upper- and lower-extremity motor control , upper-extremity function , and gait velocity . Gains for the intervention group exceeded those in the usual care group in balance , endurance , peak aerobic capacity , and mobility . Upper-extremity gains exceeded those in the usual care group only in patients with higher baseline function . CONCLUSIONS This structured , progressive program of therapeutic exercise in persons who had completed acute rehabilitation services produced gains in endurance , balance , and mobility beyond those attributable to spontaneous recovery and usual care Stein J , Krebs HI , Frontera WR , Fasoli SE , Hughes R , Hogan N : Comparison of two techniques of robot-aided upper limb exercise training after stroke . Am J Phys Med Rehabil 2004;83:720–728 . Objective : This study examined whether incorporating progressive resistive training into robot-aided exercise training provides incremental benefits over active-assisted robot-aided exercise for the upper limb after stroke . Design : A total of 47 individuals at least 1 yr poststroke were enrolled in this 6-wk training protocol . Paretic upper limb motor abilities were evaluated using clinical measures and a robot-based assessment to determine eligibility for robot-aided progressive resistive training at study entry . Subjects capable of participating in resistance training were r and omized to receive either active-assisted robot-aided exercises or robot-aided progressive resistance training . Subjects who were incapable of participating in resistance training underwent active-assisted robotic therapy and were again screened for eligibility after 3 wks of robotic therapy . Those subjects capable of participating in resistance training at 3 wks were then r and omized to receive either robot-aided resistance training or to continue with robot-aided active-assisted training . Results : One subject withdrew due to unrelated medical issues , and data for the remaining 46 subjects were analyzed . Subjects in all groups showed improvement in measures of motor control ( mean increase in Fugl-Meyer of 3.3 ; 95 % confidence interval , 2.2–4.4 ) and maximal force ( mean increase in maximal force of 3.5 N , P = 0.027 ) over the course of robot-aided exercise training . No differences in outcome measures were observed between the resistance training groups and the matched active-assisted training groups . Subjects ’ ability to perform the robotic task at the time of group assignment predicted the magnitude of the gain in motor control . Conclusion : The incorporation of robot-aided progressive resistance exercises into a program of robot-aided exercise did not favorably or negatively affect the gains in motor control or strength associated with this training , though interpretation of these results is limited by sample size . Individuals with better motor control at baseline experienced greater increases in motor control with robotic training 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 PURPOSE To determine whether isokinetic training can improve the strength of the hemiparetic knee musculature , functional mobility , and physical activity and to evaluate its effect on spasticity in long-term stroke survivors . DESIGN Nonr and omized self-controlled trial . SUBJECTS A volunteer sample of 15 community-dwelling stroke survivors of at least 6 months . INTERVENTION A 6-week ( 3 days/week , 40 minutes/day ) program consisting of warm-up , stretches , reciprocal knee extension and flexion isokinetic strengthening , and cool-down for the paretic limb . MAIN OUTCOME MEASURES Peak isokinetic hamstring and quadriceps torque , quadriceps spasticity , gait velocity , timed Up and Go , timed stair climb , and the Human Activity Profile ( HAP ) scores were recorded at baseline , after training , and 4 weeks after training cessation ( follow-up ) . RESULTS Paretic muscle strength improved after training ( p < .05 ) while tone remained consistent ( p > .87 ) . Gait velocity increased after training ( p < .05 ) and at follow-up ( p < .05 ) . Changes in stair climbing and timed Up and Go were not significant ( p > .37 ; p > .91 ) , although subjects perceived gains in their physical abilities at follow-up ( p < .01 ) . CONCLUSIONS Gains in strength and gait velocity without concomitant increases in muscle tone are possible after a short-term strengthening program for stroke survivors . The psychological benefit associated with physical activity is significant Background and Purpose — To evaluate the efficacy of supervised high-intensity progressive resistance training ( PRT ) on lower extremity strength , function , and disability in older , long-term stroke survivors . Methods — Forty-two volunteers aged 50 years and above , 6 months to 6 years after a single mild to moderate stroke , were r and omized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press ( LP ) , unilateral paretic and nonparetic knee extension ( KE ) , ankle dorsiflexion ( DF ) , and plantarflexion ( PF ) exercises . Functional performance was assessed using the 6-minute walk , stair-climb time , repeated chair-rise time , and habitual and maximal gait velocities . Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument ( LLFDI ) . Results — Single-repetition maximum strength significantly improved in the PRT group for LP ( 16.2 % ) , paretic KE ( 31.4 % ) , and nonparetic KE ( 38.2 % ) with no change in the control group . Paretic ankle DF ( 66.7 % versus −24.0 % ) , paretic ankle PF ( 35.5 % versus −20.3 % ) , and nonparetic ankle PF ( 14.7 % versus −13.8 % ) significantly improved in the PRT group compared with the control . The PRT group showed significant improvement in self-reported function and disability with no change in the control . There was no significant difference between groups for any performance-based measure of function . Conclusions — High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke , and results in reductions in functional limitations and disability OBJECTIVE To evaluate the impact of a program of muscle strengthening and physical conditioning on impairment and disability in chronic stroke subjects . DESIGN A r and omized pretest and posttest control group , followed by a single-group pretest and posttest design . SUBJECTS Thirteen community-dwelling stroke survivors of at least 9 months . INTERVENTION A 10-week ( 3 days/week ) program consisting of a warm-up , aerobic exercises , lower extremity muscle strengthening , and a cool-down . MAIN OUTCOME MEASURES Peak isokinetic torque of the major muscle groups of the affected lower limb , quadriceps and ankle plantarflexor spasticity , gait speed , rate of stair climbing , the Human Activity Profile ( HAP ) , and the Nottingham Health Profile ( NHP ) were recorded twice for the treatment group and three times for the control group . RESULTS Significant improvements were found for all the selected outcome measures ( HAP , NHP , and gait speed ) for the treatment group ( p < .001 ) . In terms of overall training effects , the 13 subjects demonstrated increases in strength of the affected major muscle groups , in HAP and NHP profiles , and in gait speed and rate of stair climbing without concomitant increases in either quadriceps or ankle plantarflexor spasticity . CONCLUSIONS The 10-week combined program of muscle strengthening and physical conditioning result ed in gains in all measures of impairment and disability . These gains were not associated with measurable changes of spasticity in either quadriceps or ankle plantarflexors BACKGROUND AND PURPOSE After stroke , many individuals have chronic unilateral motor dysfunction in the upper extremity that severely limits their functional movement control . The purpose of this study was to determine the effect of electromyography-triggered neuromuscular electrical stimulation on the wrist and finger extension muscles in individuals who had a stroke > or = 1 year earlier . METHODS Eleven individuals volunteered to participate and were r and omly assigned to either the electromyography-triggered neuromuscular stimulation experimental group ( 7 subjects ) or the control group ( 4 subjects ) . After completing a pretest involving 5 motor capability tests , the poststroke subjects completed 12 treatment sessions ( 30 minutes each ) according to group assignments . Once the control subjects completed 12 sessions attempting wrist and finger extension without any external assistance and were posttested , they were then given 12 sessions of the rehabilitation treatment . RESULTS The Box and Block test and the force-generation task ( sustained muscular contraction ) revealed significant findings ( P<0 . 05 ) . The experimental group moved significantly more blocks and displayed a higher isometric force impulse after the rehabilitation treatment . CONCLUSIONS Two lines of evidence clearly support the use of the electromyography-triggered neuromuscular electrical stimulation treatment to rehabilitate wrist and finger extension movements of hemiparetic individuals > or = 1 year after stroke . The treatment program decreased motor dysfunction and improved the motor capabilities in this group of poststroke individuals Electromyographic biofeedback was compared with simple exercise therapy as to its effectiveness in improving foot-drop in 22 stroke patients . The study was design ed to be a rigorous trial of biofeedback and the patients tested were aged and had stroke of long duration . One group of 11 patients underwent 6 weeks of exercise therapy 2 sessions per week for 15 minutes per session ; the 2nd group of 11 patients underwent similar therapy with EMG feedback . All therapy was conducted by a research assistant who was not a trained therapist . The groups were assessed blind before treatment , after treatment and a 6-week follow-up . The significantly greater improvements in the biofeedback group in terms of muscle strength at the end of treatment were maintained at follow-up . On the range of movement and gait analysis measures , both groups showed some improvement after treatment . However , at follow-up this improvement had relapsed for the exercise group while for the biofeedback group it had been maintained . It is argued that controlled trials are possible in biofeedback and that using patients as their own controls is not justified in view of the present findings and the previously reported literature A long-term , comparison-group outcome trial with a partial crossover design was carried out on the effects of electromyographic biofeedback ( EMGBF ) plus physiotherapy ( PT ) versus PT alone in the treatment of the hemiplegic upper limb in stroke patients who were at least six months beyond the onset of their disability . Both the experimental and the control groups benefited from their treatment , but EMGBF was shown to have an additional effect , both in the experimental patients , and in the control patients when they switched over to the experimental treatment condition BACKGROUND AND PURPOSE A principle of poststroke rehabilitation is that effort should be avoided since it leads to increased spasticity and produces widespread associated abnormal reactions . Although weakness also contributes to movement dysfunction after a stroke , it has been feared that heightened activity levels during strength training will further exacerbate the abnormal tone imbalance present in spastic hemiplegia . The purpose of this study was to test this hypothesis by quantifying the effects of increased workload on motor performance during different speeds of pedaling exercise in persons with poststroke hemiplegia . METHODS Twelve healthy elderly subjects and 15 subjects with poststroke hemiplegia of greater than 6 months since onset were tested . The experimental protocol consisted of having subjects pedal at 12 r and omly ordered workload and cadence combinations ( 45-J , 90-J , 135-J , and 180-J workloads at 25 , 40 , and 55 rpm ) . Pedal reaction forces were measured and used to calculate work done by each leg , including net positive and negative components . An electromyogram was recorded from seven leg muscles . RESULTS The main finding was that net mechanical work done by the plegic leg increased as workload increased in 75 of 81 instances without increasing the percentage of inappropriate muscle activity . CONCLUSIONS This study provides evidence that persons with hemiplegia increase force output by their plegic limb when pedaling against higher workloads without exacerbation of impaired motor control . Therefore , exertional pedaling exercise is a beneficial intervention for achieving gains in muscular force output without worsening motor control impairments OBJECTIVE To compare the effects of robot-assisted movement training with conventional techniques for the rehabilitation of upper-limb motor function after stroke . DESIGN R and omized controlled trial , 6-month follow-up . SETTING A Department of Veterans Affairs rehabilitation research and development center . PARTICIPANTS Consecutive sample of 27 subjects with chronic hemiparesis ( > 6mo after cerebrovascular accident ) r and omly allocated to group . INTERVENTIONS All subjects received twenty-four 1-hour sessions over 2 months . Subjects in the robot group practice d shoulder and elbow movements while assisted by a robot manipulator . Subjects in the control group received neurodevelopmental therapy ( targeting proximal upper limb function ) and 5 minutes of exposure to the robot in each session . MAIN OUTCOME MEASURES Fugl-Meyer assessment of motor impairment , FIMtrade mark instrument , and biomechanic measures of strength and reaching kinematics . Clinical evaluations were performed by a therapist blinded to group assignments . RESULTS Compared with the control group , the robot group had larger improvements in the proximal movement portion of the Fugl-Meyer test after 1 month of treatment ( P<.05 ) and also after 2 months of treatment ( P<.05 ) . The robot group had larger gains in strength ( P<.02 ) and larger increases in reach extent ( P<.01 ) after 2 months of treatment . At the 6-month follow-up , the groups no longer differed in terms of the Fugl-Meyer test ( P>.30 ) ; however , the robot group had larger improvements in the FIM ( P<.04 ) . CONCLUSIONS Compared with conventional treatment , robot-assisted movements had advantages in terms of clinical and biomechanical measures . Further research into the use of robotic manipulation for motor rehabilitation is justified OBJECTIVE To evaluate the immediate and long-term effects of 2 upper-extremity rehabilitation approaches for stroke compared with st and ard care in participants stratified by stroke severity . DESIGN Nonblinded , r and omized controlled trial ( baseline , postintervention , 9mo ) design . SETTING Inpatient rehabilitation hospital and outpatient clinic . PARTICIPANTS Sixty-four patients with recent stroke admitted for inpatient rehabilitation were r and omized within severity strata ( Orpington Prognostic Scale ) into 1 of 3 intervention groups . Forty-four patients completed the 9-month follow-up . INTERVENTIONS St and ard care ( SC ) , functional task practice ( FT ) , and strength training ( ST ) . The FT and ST groups received 20 additional hours of upper-extremity therapy beyond st and ard care distributed over a 4- to 6-week period . MAIN OUTCOME MEASURES Performance measures of impairment ( Fugl-Meyer Assessment ) , strength ( isometric torque ) , and function ( Functional Test of the Hemiparetic Upper Extremity [ FTHUE ] ) . RESULTS Compared with SC participants , those in the FT and ST groups had significantly greater increases in Fugl-Meyer motor scores ( P=.04 ) and isometric torque ( P=.02 ) posttreatment . Treatment benefit was primarily in the less severe participants , where improvement in FT and ST group Fugl-Meyer motor scores more than doubled that of the SC group . Similar results were found for the FTHEU and isometric torque . During the long term , at 9 months , the less severe FT group continued to make gains in isometric muscle torque , significantly exceeding those of the ST group ( P<.05 ) . CONCLUSIONS Task specificity and stroke severity are important factors for rehabilitation of arm use in acute stroke . Twenty hours of upper extremity-specific therapy over 4 to 6 weeks significantly affected functional outcomes . The immediate benefits of a functional task approach were similar to those of a resistance-strength approach , however , the former was more beneficial in the long-term Positional feedback stimulation training and cyclical electrical stimulation were used in combination as a treatment for facilitating knee extension in hemiparetic patients . Forty adult hemiparetic patients who demonstrated minimal active control of their quadriceps femoris muscles were r and omly assigned to control or study groups . The control patients received a program of physical therapy , and the study patients received the positional feedback stimulation training in addition to their therapy program . The stimulation training provided the patient with immediate auditory and visual feedback of his changing joint angle while he voluntarily extended his knee . When the patient reached a near maximal extension effort , electrical stimulation of the quadriceps femoris muscle was automatically triggered , completing the patient 's available range of motion in extension . The stimulation training was supplemented with two hours of cyclical electrical stimulation daily . At the end of four weeks , analysis revealed a statistically significant increase in knee extension torque and active synergistic range of motion in the study group . No change was noted in their ability to extend their knees using isolated quadriceps femoris muscle control . This study suggests that positional feedback stimulation training is effective when used to augment a facilitation program for improving knee extension control in hemiparetic patients 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 . The effectiveness of biofeedback training was compared to conventional physical therapy training in 20 adult hemiparetic patients with chronic foot-drop . They were r and omly placed into two groups of ten patients each : the first group treated over five weeks with therapeutic exercise and the second group treated over five weeks with therapeutic exercise plus biofeedback training . In the second group receiving the biofeedback training the increase in both strength and range of motion was approximately twice as great as in the first group . The improvement displayed by even the first group of patients suggests that a potential for functional improvement exists that is often unexploited . The addition of biofeedback facilitates the process . Four patients in the biofeedback group achieved and retained conscious control of dorsiflexion ; three of them are now able to walk without the use of the short leg brace A group of forty-nine hemiparetic patients with limited emotional , communication and sensibility involvement and with recent lesion of cerebrovascular aetiology was r and omly divided into two groups of twenty-four and twenty-five subjects . Both groups received traditional physiotherapy treatment for one hour/day , one group received twenty min/day of peroneal nerve stimulation . The maximum voluntary dorsal flexion moments of the ankle joint of the affected and non affected extremities were measured with an isometric brace twice a week for one month and for both groups . The recovery of moment in the stimulated group turned out to be about three times greater than in the control group and considerably less dependent upon age , time from lesion , initial value , side of lesion . Three patients using a peroneal brace at home as an assisting device were again evaluated two months later and a further improvement was observed . This work gives statistical support to previous observations based on very few cases and provides a statistically reliable answer concerning the entity of FES induced recovery of muscle force in hemiparetic subjects The purpose of this article is to describe the relationship between poststroke upper limb muscle weakness and cocontraction , and clinical measures of upper limb motor impairment and physical disability . Electromyographic ( EMG ) activity of the paretic and nonparetic wrist flexors and extensors of 26 chronic stroke survivors were recorded during isometric wrist flexion and extension . The root mean square ( RMS ) of the EMG signal was used as a measure of strength of contraction . A ratio of RMS of antagonist and agonist muscles was used as a measure of cocontraction . Upper limb motor impairment and physical disability were assessed with the Fugl-Meyer motor assessment ( FMA ) and the arm motor ability test ( AMAT ) , respectively . The strength of muscle contraction was significantly stronger in the nonparetic limb ( P < 0.001 ) . The degree of cocontraction was significantly greater in the paretic limb ( P < 0.001 ) . The strength of muscle contraction in the paretic limb correlated significantly with FMA ( r = 0.62 to 0.87,P ≤ 0.001 ) and AMAT ( r = 0.66 to 0.80 , P ≤ 0.001 ) scores . Similarly , the degree of cocontraction correlated significantly with FMA ( r = -0.70 to -0.64 , P ≤ 0.001 ) and AMAT ( r = -0.72 to -0.62 , P ≤ 0.001 ) scores . Muscle weakness and degree of cocontraction correlate significantly with motor impairment and physical disability in upper limb hemiplegia . This relationship may provide insights toward development of specific interventions . However , additional studies are needed to demonstrate a cause and effect relationship OBJECTIVES The goal most often stated by persons with stroke is improved walking function . The purpose of this study was to determine the effects of isokinetic strength training on walking performance , muscle strength , and health-related quality of life in survivors of chronic stroke . METHODS Twenty participants ( age , 61.2 + /- 8.4 years ) with chronic stroke were r and omized into 2 groups . The experimental group undertook maximal concentric isokinetic strength training , whereas the control group received passive range of motion of the paretic lower extremity 3 times a week for 6 weeks . The Kin-Com Isokinetic Dynamometer ( Chattanooga Group Inc. , TN ) was used for both the strengthening and passive range of motion exercises . The Mann-Whitney U test was used to compare the changes in scores ( postintervention minus baseline ) between the control and experimental groups for a composite lower extremity strength score , walking speed ( level-walking and stair-walking ) and health-related quality of life measure ( 36-Item Short Form Health Survey [ SF-36 ] ) . RESULTS Both the experimental and control groups increased their strength and walking speed postintervention ; however , there were no differences in the changes in walking speed between the groups . There was a trend ( P = .06 ) toward greater strength improvement in the experimental group compared with the control group . No changes in SF-36 scores were found in either group . CONCLUSIONS Intervention aim ed at increasing strength did not result in improvements in walking . The results of this study stress the importance of controlled clinical trials in determining the effect of specific treatment approaches . Strength training in conjunction with other task-related training may be indicated |
11,143 | 29,393,662 | Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD , but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal ( HPA ) axis , the levels of estradiol , serotonin , pro-inflammatory cytokines , and /or of other mechanisms involved in PPD | ABSTRACT Postpartum depression ( PPD ) is a prevalent mood disorder estimated to affect 20%–40 % of women worldwide after childbirth .
In recent studies , the effect of vitamin D on prevention of mood disorders and depression has been investigated , but it is still unclear how vitamin D may affect PPD .
The evidence on the relevance between vitamin D deficiency and PPD is inconsistent , and assessment of the recent literature has not previously been carried out .
Moreover , there are few clinical studies on PPD and vitamin D supplementation . | The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antioxidant capacity , transforming growth factor β1 , as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention . In patients who received vitamin D supplement compared to the controls , the median of serum 25(OH)D3 significantly increased ( 16.2 vs. 1.6 ng/ml , P < 0.001 ) . This increase accompanied by significant decrease in serum MDA ( −2.09 vs. −1.23 ng/ml , P = 0.03 ) and near significant changes in serum hs-CRP ( −0.25 vs. 0.22 mg/l , P = 0.06 ) . These between-group differences remained significant even after controlling for baseline covariates . Other variables showed no significant changes . Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD . This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients Abstract Mood changes synchronised to the seasons exist on a continuum between individuals , with anxiety and depression increasing during the winter months . An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder ( SAD ) with carbohydrate craving , hypersomnia , lethargy , and changes in circadian rhythms also evident . It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3 , the hormone of sunlight , leading to changes in brain serotonin . Forty-four healthy subjects were given 400 IU , 800 IU , or no vitamin D3 for 5 days during late winter in a r and om double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect . Results are discussed in terms of their implication s for seasonality , SAD , serotonin , food preference , sleep , and circadian rhythms Pregnancy is a time of vulnerability for vitamin D insufficiency , and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms . However , the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined . We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms . We prospect ively collected sera at 18 weeks gestation from 796 pregnant women in Perth ( 1989–1992 ) who were enrolled in the Western Australian Pregnancy Cohort ( Raine ) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery . Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D , even after accounting for a range of confounding variables including season of birth , body mass index and sociodemographic factors . Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms OBJECTIVES Postpartum depression ( PPD ) is a common disorder that affects 10 - 15 % of postpartum women , and it can have negative effects on both the mother and newborn . Recent studies have suggested that low levels of vitamin D are associated with poor mood and depression . The aim of this prospect i ve study was to evaluate a possible association between PPD and serum levels of 25-hydroxy vitamin D3 ( 25(OH)D3 ) , a reliable measurement of vitamin D , during mid-pregnancy . STUDY DESIGN The source population consisted of all pregnant women between 24 and 28 gestational weeks from June 2012 to October 2012 at Bornova Health Research and Application Hospital , Sifa University . In order to better evaluate a possible effect between vitamin D levels and PPD , individuals with characteristics that put them at risk for developing PPD were excluded from the study . Serum 25(OH)D3 levels were evaluated mid-pregnancy in the study group . Serum 25(OH)D3 concentrations ≤20ng/mL ( 50nmol/L ) were classified as a mild deficiency and those ≤10ng/mL ( 25nmol/L ) were classified as a severe deficiency . Pregnant subjects having complications during birth or with the newborn after delivery were excluded from the study . The Edinburgh Postnatal Depression Scale ( EPDS ) was used to assess maternal PPD 1 week , 6 weeks , and 6 months after delivery . A Pearson correlation was used to measure the strength of the associations between the EPDS scores and vitamin D levels analyzed during the three time periods . A logistic regression analysis was used to determine the independent effects of vitamin D on PPD . RESULTS Six hundred and eighty-seven pregnant women were included in this study . After excluding women due to PPD risk factors ( in two stages ) , 179 pregnant women were screened for vitamin D levels during mid-pregnancy and in the 6th month postpartum . Eleven percent of our study group had severe vitamin D deficiency and 40.3 % had mild vitamin D deficiency . The frequency of PPD was 21.6 % at the 1st week , 23.2 % at 6th week , and 23.7 % at the 6th month . There was a significant relationship between low 25(OH)D3 levels in mid-pregnancy and high EPDS scores , which is indicative of PPD for all three follow-up periods ( p=0.003 , p=0.004 and p<0.001 , respectively ) . In addition , there was a significant negative correlation between vitamin D levels and EDPS at all three time points ( r=-0.2 , -0.2 , -0.3 , respectively ) . CONCLUSIONS Vitamin D deficiency in mid-pregnancy may be a factor affecting the development of PPD . More extensive studies are required to be carried out on this subject Vitamin D deficiency and elevated pro-inflammatory cytokines have each been associated individually with postpartum depression ( PPD ) . African American women are at increased risk for prenatal vitamin D deficiency , inflammation , and prenatal and postpartum depressive symptoms , but biological risk factors for PPD in this population have rarely been tested . This prospect i ve study tested whether low prenatal vitamin D status ( serum 25-hydroxyvitamin D , 25[OH]D ) predicted PPD symptomatology in pregnant African American women and whether high levels of prenatal inflammatory cytokines interacted with low 25(OH)D in effects on PPD symptoms . Vitamin D status was measured in the first trimester in a sample of 91 African American pregnant women who had a second trimester blood sample assayed for inflammatory markers . Depressive symptoms were assessed at a postpartum visit . An inverse association between prenatal log 25(OH)D and PPD symptomatology approached significance ( β = −0.209 , p = 0.058 ) , and interleukin-6 and IL-6/IL-10 ratio significantly moderated the effect . Among women with higher levels of inflammatory markers , lower prenatal log 25(OH)D was associated with significantly higher PPD symptoms ( p < 0.05 ) . These preliminary results are intriguing because , if replicable , easy translational opportunities , such as increasing vitamin D status in pregnant women with elevated pro-inflammatory cytokines , may reduce PPD symptoms BACKGROUND Postpartum depression ( PPD ) is a widespread worldwide phenomenon , but its etiology remains unclear . This study reappraised how evolutionary theory could explain PPD as an adaptation through investigating the relationship between maternal age and PPD , and if this relationship is modified according to the number of children at home . METHODS A cross-sectional study carried out in five primary health care units included 811 participants r and omly selected among mothers of children up to five postpartum months in Rio de Janeiro , Brazil . Postpartum depression was defined by scores above 11 on Edinburgh Postnatal Depression Scale ( EPDS ) , and statistical analysis was based on multivariate logistic regression models . RESULTS One hundred and ninety-seven ( 24.3 % , CI 95 % 21.3 - 27.2 ) participants were classified as PPD positives . Maternal age was significantly associated to PPD ( OR=0.96 , p-value=0.019 ) independently of socioeconomic and reproductive characteristics , conjugal status or substance consumption by the couple . Thus , for each additional year , a reduction of 4 % in the chance of developing PPD could be anticipated , effect which was not modified by the number of children at home ( p-value=0.602 ) . LIMITATIONS Information on social support was not included in this analysis since its relationship with maternal mental health would be better evaluated in a prospect i ve fashion . CONCLUSIONS These findings suggest that adaptive mechanisms shaped through human generations persist contributing to the development of PPD in contemporary societies . According to this evolutionary approach , as maternal age advances the reproductive potential diminishes and , consequently , mothers are less prone to develop PPD and reduce investment in new offspring |
11,144 | 11,155,833 | Previous research has suggested that method ologically poorly design ed studies tend to over-estimate the effect estimate .
Our study does not confirm these conclusions | OBJECTIVE This study investigates the influence of different aspects of method ologic quality on the conclusions of a systematic review concerning treatments of acute lateral ankle sprain . | One hundred and forty-three patients presenting with ankle sprains within 24 h of injury were entered into a double blind study . Treatment consisted of a st and ardized regime of high dose non-steroidal anti-inflammatory medication and an elastic support for all patients , who were then r and omly allocated to two groups . One group received immediate cold therapy , the other received simulated therapy . Assessment s made at 7 days showed a trend in favour of the group receiving cold therapy , although this did not reach significance . It is concluded that cold therapy together with compression may have a beneficial effect but that a single application in the accident and emergency department is not justified when a background therapy of non-steroidal anti-inflammatory medication is given Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports A r and omized , controlled parallel-group trial has assessed 14 days ' use of a new ankle support ( Malleotrain , Bauerfeind , Aldershot , UK ) in 220 patients ( 118 Malleotrain , 102 control group ) with acute ankle injuries . Self-assessed pain levels were significantly lower in the group using Malleotrain at the end of the trial ( P less than 0.05 ) , as were median times taken for reduction of symptom scores to 10 % ( P less than 0.05 ) and total analgesic consumption during the trial ( P less than 0.05 ) . Overall clinical assessment scores were significantly superior in the Malleotrain group ( P less than 0.02 ) . Of those patients who received Malleotrain , 112 of 116 patients who commented ( 95 % of all Malleotrain-treated patients ) did so positively and only one patient stopped wearing the support during the trial . Malleotrain is acceptable to patients with acute ankle injuries and its use increases the rate of alleviation of symptoms . Its use should therefore be considered in the management of all such patients We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Abstract Objective : To assess the method ological quality of approaches to blinding and to h and ling of exclusions as reported in r and omised trials from one medical specialty . Design : Survey of published , parallel group r and omised controlled trials . Data sources : A r and om sample of 110 reports in which allocation was described as r and omised from the 1990 and 1991 volumes of four journals of obstetrics and gynaecology . Main outcome measures : The adequacy of the descriptions of double blinding and exclusions after r and omisation . Results : Though 31 trials reported being double blind , about twice as many could have been . Of the 31 trials only eight ( 26 % ) provided information on the protection of the allocation schedule and only five ( 16 % ) provided some written assurance of successful implemention of double blinding . Of 38 trials in which the authors provided sufficient information for readers to infer that no exclusions after r and omisation had occurred , six ( 16 % ) reported adequate allocation concealment and none stated that an intention to treat analysis had been performed . That compared with 14 ( 27 % ) and six ( 12 % ) , respectively , for the 52 trials that reported exclusions . Conclusions : Investigators could have double blinded more often . When they did double blind , they reported poorly and rarely evaluated it . Paradoxically , trials that reported exclusions seemed generally of a higher method ological st and ard than those that had no apparent exclusions . Exclusions from analysis may have been made in some of the trials in which no exclusions were reported . Editors and readers of reports of r and omised trials should underst and that flawed reporting of exclusions may often provide a misleading impression of the quality of the trial . Key messages Key messages Poor reporting of methods used for double blinding raises concerns about how effective blinding was in many of the studies Some investigators may have excluded some patients from the analysis but not reported these exclusions in their published paper Given the apparent failure to report exclusions , some of the more biased trials may be mistaken as unbiased and vice versa Investigators must pay more attention to executing and reporting their approaches to blinding and the h and ling of Eighty patients with grade III lateral ligament ruptures were treated either with total immobilization in a walking plaster cast or early mobilization in a stabilizing orthosis . The criterion for entrance was a talar tilt of more than 9 ° and an anterior translation of more than 10 mm at stress radiography , a previously stable ankle , and a contralateral ankle showing normal stress radiographic values . Ninety-one percent of the patients were evaluated at 7 weeks , 3 months , and 1 year postinjury . While functionally treated patients reached normal mobility and resumed work and sports earlier than immobilized patients there were no differences between the treatment groups in ankle stability or symptoms during activity after 1 year . Ninety-five percent of the ankles in either group were mechanically stable after treatment . Residual symptoms were present 1 year postinjury in 13 % of the functionally treated ankles and in 9 % of the cast-mobilized ankles . In lateral ankle ligament ruptures causing gross mechanical instability early mobilization results in a better early functional result ; however , at 1 year postinjury there was no statistically significant difference in outcome as compared to cast-immobilized ankles We analysed the results of 221 comparisons of an innovation with a st and ard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain . For each comparison we measured the gain attributed to the innovation over the st and ard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes . For primary treatments ( aim ed at curing or ameliorating a patient 's principal disease ) , an average gain of 0.56 was produced by 20 r and omized controlled trials . This was less than the 0.62 average for four non-r and omized controlled trials , 0.63 for 19 externally controlled trials , and 0.57 for 73 record review s ( 0.50 represents a toss-up between innovation and st and ard ) . For secondary therapies ( used to prevent or treat complications of therapy ) , the average gain was 0.53 for 61 r and omized controlled trials , 0.58 for eleven non-r and omized controlled trials , 0.54 for eight externally controlled trials , and 0.55 for 18 record review s. Readers of studies evaluating new treatments , particularly for primary treatments , may consider adjustment of the gain according to the study type A support for the treatment of stable injuries of the lateral ligament of the ankle has been design ed . One hundred and seventy-five consecutive patients with acute injuries were studied . Unstable injuries were excluded by the use of the radiological anterior stress test . One hundred and forty-four patients with stable injuries were r and omly allocated to three treatment groups : double Tubigrip , eversion strapping and the new support . The change in the range of movement was used as an objective measure of improvement . The new support was noticeably better than Tubigrip and eversion strapping Acutely sprained ankles represent a frequent and common injury among active duty troops in training , and are a significant source of morbidity with respect to days lost to training . Swelling in the form of periarticular edema limits motion , causes pain , prevents wearing of normal foot gear , and slows the healing process . Reduction of edema was attempted in acutely sprained ankles by the use of pulsed electromagnetic energy ( Diapulse ) . In a r and omized , prospect i ve , double blind study of 50 grade I and II ( no gross instability ) sprained ankles , a statistically significant ( p < 0.01 ) decrease in edema was noted following one treatment with Diapulse . The application of this modality in acutely sprained ankles could result in significant decreases in time lost to military training The purpose of this study was to compare the effects of three treatment protocol s on pitting edema in patients with first- and second-degree sprained ankles . Thirty subjects with postacute ( greater than 24 hours postinjury ) ankle sprains and pitting edema but not requiring cast immobilization were r and omly assigned to an elastic wrap group ( N = 10 ) , an intermittent compression group ( N = 10 ) , or an elevated control group ( N = 10 ) . Pretreatment and posttreatment volumetric measurements of the subjects ' ankles were obtained by the water displacement method . After the pretreatment measurement , the groups were treated for 30 minutes . All subjects ' ankles were elevated by raising the foot section of an adjustable table to a 45 degrees angle during treatment . For the first treatment group , the intermittent compression device was set at 40 - 50 mm Hg , with a 60-second on time and a 15-second off time . For the second treatment group , an elastic wrap was applied from the heads of the metatarsals to 12.7 centimeters above the malleoli . Control group subjects received only the elevated position as their treatment . A three by two repeated measures ANOVA with a follow-up post hoc test revealed that the elevated control group subjects had the least amount of edema ( p < .0006 ) . The two compression protocol s produced increased edema in the subjects ' sprained ankles following treatment . In conclusion , elevation is the most appropriate of the three treatment protocol s if the major therapeutic objective is to minimize edema in the postacute phase of rehabilitation . J Orthop Sports Phys Ther 1991;14(2):65 - 69 |
11,145 | 29,209,504 | Conclusion The FIFA 11 + warm-up program reduced the risk of injury in soccer players by 30 % | Background Soccer is one of the most widely played sports in the world .
However , soccer players have an increased risk of lower limb injury .
These injuries may be caused by both modifiable and non-modifiable factors , justifying the adoption of an injury prevention program such as the Fédération Internationale de Football Association ( FIFA ) 11 + .
The purpose of this study was to evaluate the efficacy of the FIFA 11 + injury prevention program for soccer players . | Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Objective To study the injury characteristics in professional football and to follow the variation of injury incidence during a match , during a season and over consecutive seasons . Design Prospect i ve cohort study where teams were followed for seven consecutive seasons . Team medical staff recorded individual player exposure and time-loss injuries from 2001 to 2008 . Setting European professional men 's football . Participants The first team squads of 23 teams selected by the Union of European Football Associations as belonging to the 50 best European teams . Main outcome measurement Injury incidence . Results 4483 injuries occurred during 566 000 h of exposure , giving an injury incidence of 8.0 injuries/1000 h. The injury incidence during matches was higher than in training ( 27.5 vs 4.1 , p<0.0001 ) . A player sustained on average 2.0 injuries per season , and a team with typically 25 players can thus expect about 50 injuries each season . The single most common injury subtype was thigh strain , representing 17 % of all injuries . Re-injuries constituted 12 % of all injuries , and they caused longer absences than non re-injuries ( 24 vs 18 days , p<0.0001 ) . The incidence of match injuries showed an increasing injury tendency over time in both the first and second halves ( p<0.0001 ) . Traumatic injuries and hamstring strains were more frequent during the competitive season , while overuse injuries were common during the preseason . Training and match injury incidences were stable over the period with no significant differences between seasons . Conclusions The training and match injury incidences were stable over seven seasons . The risk of injury increased with time in each half of matches Purpose We aim ed to investigate the effect of FIFA 11 + ( 11 + ) and HarmoKnee injury preventive warm-up programs on conventional strength ratio ( CSR ) , dynamic control ratio ( DCR ) and fast/slow speed ratio ( FSR ) in young male professional soccer players . These ratios are related to the risk of injury to the knee in soccer players . Methods Thirty-six players were divided into 3 groups ; FIFA 11 + , HarmoKnee and control ( n = 12 per group ) . These exercises were performed 3 times per week for 2 months ( 24 sessions ) . The CSR , DCR and FSR were measured before and after the intervention . Results After training , the CSR and DCR of knee muscles in both groups were found to be lower than the published normal values ( 0.61 , 0.72 , and 0.78 during 60 ° .s−1 , 180 ° .s−1 and 300 ° .s−1 , respectively ) . The CSR ( 60 ° .s−1 ) increased by 8 % and FSR in the quadriceps of the non-dominant leg by 8 % in the 11 + . Meanwhile , the DCR in the dominant and non-dominant legs were reduced by 40 % and 30 % respectively in the 11 + . The CSR ( 60 ° .s−1 ) in the non-dominant leg showed significant differences between the 11 + , HarmoKnee and control groups ( p = 0.02 ) . As for the DCR analysis between groups , there were significant differences in the non-dominant leg between both programs with the control group ( p = 0.04 ) . For FSR no significant changes were found between groups . Conclusions It can be concluded that the 11 + improved CSR and FSR , but the HarmoKnee program did not demonstrate improvement . We suggest adding more training elements to the HarmoKnee program that aim ed to enhance hamstring strength ( CSR , DCR and FSR ) . Professional soccer players have higher predisposition of getting knee injuries because hamstring to quadriceps ratio were found to be lower than the average values . It seems that the 11 + have potentials to improve CSR and FSR as well as prevent knee injuries in soccer players Background : The Fédération Internationale de Football Association ( FIFA ) 11 + program has been shown to be an effective injury prevention program in the female soccer cohort , but there is a paucity of research to demonstrate its efficacy in the male population . Hypothesis : To examine the efficacy of the FIFA 11 + program in men ’s collegiate United States National Collegiate Athletic Association ( NCAA ) Division I and Division II soccer . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Before the commencement of the fall 2012 season , every NCAA Division I and Division II men ’s collegiate soccer team ( N = 396 ) was solicited to participate in this research study . Human ethics review board approval was obtained through Quorum Review IRB . Sixty-five teams were r and omized : 34 to the control group ( CG ; 850 players ) and 31 to the intervention group ( IG ; 675 players ) . Four teams in the IG did not complete the study , reducing the number for analysis to 61 . The FIFA 11 + injury prevention program served as the intervention and was utilized weekly . Athlete-exposures ( AEs ) , compliance , and injury data were recorded using a secure Internet-based system . Results : In the CG , 665 injuries ( mean ± SD , 19.56 ± 11.01 ) were reported for 34 teams , which corresponded to an incidence rate ( IR ) of 15.04 injuries per 1000 AEs . In the IG , 285 injuries ( mean ± SD , 10.56 ± 3.64 ) were reported for 27 teams , which corresponded to an IR of 8.09 injuries per 1000 AEs . Total days missed because of injury were significantly higher for the CG ( mean ± SD , 13.20 ± 26.6 days ) than for the IG ( mean ± SD , 10.08 ± 14.68 days ) ( P = .007 ) . There was no difference for time loss due to injury based on field type ( P = .341 ) . Conclusion : The FIFA 11 + significantly reduced injury rates by 46.1 % and decreased time loss to injury by 28.6 % in the competitive male collegiate soccer player ( rate ratio , 0.54 [ 95 % CI , 0.49 - 0.59 ] ; P < .0001 ) ( number needed to treat = 2.64 ) A prospect i ve study of injuries encountered during participation in a summer soccer camp for youths aged 6 through 17 years revealed an injury incidence of 10.6 per 1000 hours for girls ( 107 injuries in 458 girls ) and 7.3 per 1000 hours for boys ( 109 injuries in 681 boys ) . For both sexes , the incidence of injury increased at age 14 years . One certified athletic trainer ( W.D.C. ) assessed and documented all injuries during the course of the study . Seventy percent of injuries involved the lower extremities . Contusions represented 35.2 % , strains 27.8 % , sprains 19.4 % , and fractures and dislocations 2 % of all reported injuries . The ankle was the most frequent site of injury in both sexes . Quadriceps strain was a common injury in boys . The boys with the highest incidence of injury were tall ( greater than 165 cm ) and had a weak grip ( less than 25 kg ) , suggesting that skeletally mature but muscularly weak boys may be more susceptible to injury while playing soccer with peers of the same chronological age Objective To examine the effect of a comprehensive warm-up programme design ed to reduce the risk of injuries in female youth football . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 125 football clubs from the south , east , and middle of Norway ( 65 clusters in the intervention group ; 60 in the control group ) followed for one league season ( eight months ) . Participants 1892 female players aged 13 - 17 ( 1055 players in the intervention group ; 837 players in the control group ) . Intervention A comprehensive warm-up programme to improve strength , awareness , and neuromuscular control during static and dynamic movements . Main outcome measure Injuries to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . Results During one season , 264 players had relevant injuries : 121 players in the intervention group and 143 in the control group ( rate ratio 0.71 , 95 % confidence interval 0.49 to 1.03 ) . In the intervention group there was a significantly lower risk of injuries overall ( 0.68 , 0.48 to 0.98 ) , overuse injuries ( 0.47 , 0.26 to 0.85 ) , and severe injuries ( 0.55 , 0.36 to 0.83 ) . Conclusion Though the primary outcome of reduction in lower extremity injury did not reach significance , the risk of severe injuries , overuse injuries , and injuries overall was reduced . This indicates that a structured warm-up programme can prevent injuries in young female football players . Trial registration IS RCT N10306290 Background : Muscle injuries constitute a large percentage of all injuries in football . Purpose : To investigate the incidence and nature of muscle injuries in male professional footballers . Study Design : Cohort study ; Level of evidence , 2 . Methods : Fifty-one football teams , comprising 2299 players , were followed prospect ively during the years 2001 to 2009 . Team medical staff recorded individual player exposure and time-loss injuries . The first-team squads of 24 clubs selected by the Union of European Football Associations as belonging to the best European teams , 15 teams of the Swedish First League , and another 15 European teams playing their home matches on artificial turf pitches were included . A muscle injury was defined as “ a traumatic distraction or overuse injury to the muscle leading to a player being unable to fully participate in training or match play . ” Results : In total , 2908 muscle injuries were registered . On average , a player sustained 0.6 muscle injuries per season . A squad of 25 players can thus expect about 15 muscle injuries per season . Muscle injuries constituted 31 % of all injuries and caused 27 % of the total injury absence . Ninety-two percent of all muscle injuries affected the 4 major muscle groups of the lower limbs : hamstrings ( 37 % ) , adductors ( 23 % ) , quadriceps ( 19 % ) , and calf muscles ( 13 % ) . Sixteen percent of the muscle injuries were reinjuries . These reinjuries caused significantly longer absences than did index injuries . The incidence of muscle injury increased with age . When separated into different muscle groups , however , an increased incidence with age was found only for calf muscle injuries and not for hamstring , quadriceps , or hip/groin strains . Conclusion : Muscle injuries are a substantial problem for players and their clubs . They constitute almost one third of all time-loss injuries in men ’s professional football , and 92 % of all injuries affect the 4 big muscle groups in the lower limbs In this prospect i ve study , injuries in 153 adolescent female soccer players were recorded during one outdoor season ( April-October ) . The overall injury incidence rate was 6.8 per 1000 h soccer ( games and practice ) and the incidence rate of traumatic injury 9.1 and 1.5 per 1000 player-hours in games and practice , respectively . Sixty-three players ( 41 % ) sustained 79 injuries . Sixty-six percent of the injuries were traumatic and 34 % were overuse injuries . Most of the traumatic injuries occurred during games . Eighty-nine percent of the injuries were located in the lower extremities and 42 % occurred in the knee or ankle . The most frequent type of injury was ankle sprain ( 22.8 % ) . Forty-one percent of the traumatic injuries and 56 % of the ankle sprains were re-injuries . Most of the injuries were of moderate severity ( 52 % ) , while 34 % were minor and 14 % were major . Most of the major injuries were traumatic such as knee ligament injuries and ankle sprains Background : Despite the growing popularity of women ’s football and the increasing number of female players , there has been little research on injuries sustained by female football players . Purpose : Analysis of the incidence , characteristics and circumstances of injury in elite female football players in top-level international tournaments . Study design : Prospect i ve survey . Methods : Injuries incurred in seven international football tournaments were analysed using an established injury report system . Doctors of all participating teams reported all injuries after each match on a st and ardised injury reporting form . The mean response rate was 95 % . Results : 387 injuries were reported from 174 matches , equivalent to an incidence of 67.4 injuries/1000 player hours ( 95 % CI 60.7 to 74.1 ) or 2.2 injuries/match ( 95 % CI 2.0 to 2.4 ) . Most injuries ( 84 % ; 317/378 ) were caused by contact with another player . The injuries most commonly involved the lower extremity ( n = 248 ; 65 % ) , followed by injuries of the head and neck ( n = 67 , 18 % ) , trunk ( n = 33 , 9 % ) and upper extremity ( n = 32 , 8 % ) . Contusions ( n = 166 ; 45 % ) were the most frequent type of injury , followed by sprains or ligament rupture ( n = 96 ; 26 % ) and strains or muscle fibre ruptures ( n = 31 ; 8 % ) . The most common diagnosis was an ankle sprain . There were 7 ligament ruptures and 15 sprains of the knee . On average 1 injury/match ( 95 % CI 0.8 to 1.2 ) was expected to result in absence from a match or training . Conclusion : The injury rate in women ’s top-level tournaments was within the range reported previously for match injuries in elite male and female players . However , the diagnoses and mechanisms of injury among the female players differed substantially from those previously reported in male football players A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low OBJECTIVES To compare the incidence and characteristics of injuries between Dutch amateur and professional male soccer players during one entire competition season . DESIGN A prospect i ve two-cohort design . METHODS During the 2009 - 2010 season , 456 Dutch male amateur soccer players and 217 professional players were prospect ively followed . Information on injuries and individual exposure to all soccer activities were recorded in both cohorts . Injuries were recorded using the time-loss definition . RESULTS In total , 424 injuries were recorded among 274 of the amateur players ( 60.1 % injured players ) and 286 injuries were sustained by 136 ( 62.7 % injured players ) of the professional players ( p=0.52 ) . Compared to the professionals , the injury incidence during training sessions was higher among amateurs ( p=0.01 ) , but the injury incidence among professionals was higher during matches ( p<0.001 ) . Professional players also had a higher incidence of minimal injuries ( p<0.001 ) , whereas the incidence of moderate and severe injuries was higher for amateurs ( all p<0.001 ) . Lastly , professional players sustained more overuse injuries ( p=0.02 ) , whereas amateurs reported more recurrent injuries ( p<0.001 ) . CONCLUSIONS The above-mentioned differences in injury rates between amateur and professional players in the Netherl and s might be explained by the difference in the level at which they play , since factors like the availability of medical support and /or the team size may influence the injury risk and characteristics Objectives : In review ing the literature on sports injuries , few studies could be found in which exposure related incidences of injury in different types of sport were compared . These studies indicated that ice hockey , h and ball , basketball , soccer , and rugby are popular team sports with a relatively high risk of injury . The aim of the study was to compare the characteristics and incidence of injuries in male youth amateur soccer and rugby players . Methods : This prospect i ve cohort study comprised an initial baseline examination to ascertain the characteristics of the players and their level of performance , and a one season observation period during which a physician visited the team weekly and documented all occurring injuries . Twelve soccer and 10 rugby school teams with male amateur players aged 14–18 years were selected for the study . 145 soccer and 123 rugby players could be followed up over one season . Results : Comparison of the incidence of soccer and rugby injuries indicated that rugby union football was associated with a significantly higher rate of injury than soccer . The differences were pronounced for contact injuries , injuries of the head , neck , shoulder , and upper extremity , as well as for concussion , fractures , dislocations , and strains . Rugby players incurred 1.5 times more overuse and training injuries in relation to exposure time , and 2.7 times more match injuries than soccer players . Three rugby players but no soccer players had to stop their participation in sport because of severe injury . Conclusion : The incidence of injury in New Zeal and school teams playing soccer or rugby union is high , probably in part because of the low ratio of hours spent in training relative to hours spent playing matches . The development and implementation of preventive interventions to reduce the rate and severity of injury is recommended The FIFA 11 + is a structured warm-up programme specially design ed to prevent injuries among football players from age 14 years and above . However , studies to prove its efficacy are generally few and it is yet to be tested in male youth footballers and among African players . The purpose of the study was to examine the efficacy of the FIFA 11 + programme in reducing the risk of injuries among male youth football players of the Lagos Junior League . A cluster r and omised controlled trial was conducted . All the 20 teams ( 414 players aged 14 -19 years ) in the Premier League division were block-r and omised into either an intervention ( INT ) or a control ( CON ) group . The INT group performed the FIFA 11 + exercises as warm-up during training sessions and the CON group performed usual warm-up . Participating teams were prospect ively followed through an entire league season of 6 months in which they were visited every week to assess injured players for time-loss injuries in both groups . The primary outcomes were any injury to the players , injuries by type of exposure and injuries specific to the lower extremities . The secondary outcomes were injuries reported by body location , aetiology , mechanism and severity . In total , 130 injuries were recorded affecting 104 ( 25 % ) of the 416 players . Team and player compliance with the INT was 60 % and 74 % respectively . Based on the primary outcome measures of the study , the FIFA 11 + programme significantly reduced the overall rate of injury in the INT group by 41 % [ RR = 0.59 ( 95 % CI : 0.40 - 0.86 ; p = 0.006 ) ] and all lower extremity injuries by 48 % [ RR = 0.52 ( 95 % CI : 0.34 - 0.82 ; p = 0.004 ) ] . However , the rate of injury reduction based on secondary outcomes mostly did not reach the level of statistical significance . The FIFA 11 + programme is effective in reducing the rates of injuries in male youth football players . Key pointsThe FIFA 11 + has only been tested in r and omised controlled trials conducted on female youth football players ; this study reports its efficacy in male youth football for the first timeThe FIFA 11 + programme significantly reduced the overall rate of injuries and lower extremity injuries in male youth football playersYouth football administrators in Africa and other parts of the world should pursue the implementation of the FIFA 11 + in order to minimize the incidence of injuries among players Objectives : To undertake a prospect i ve epidemiological study of the injuries sustained in English youth academy football over two competitive seasons . Methods : Player injuries were annotated by medical staff at 38 English football club youth academies . A specific injury audit question naire was used together with a weekly return form that documented each club ’s current injury status . Results : A total of 3805 injuries were reported over two complete seasons ( June to May ) with an average injury rate of 0.40 per player per season . The mean ( SD ) number of days absent for each injury was 21.9 ( 33.63 ) , with an average of 2.31 ( 3.66 ) games missed per injury . The total amount of time absent through injury equated to about 6 % of the player ’s development time . Players in the higher age groups ( 17–19 years ) were more likely to receive an injury than those in the younger age groups ( 9–16 years ) . Injury incidence varied throughout the season , with training injuries peaking in January ( p<0.05 ) and competition injuries peaking in October ( p<0.05 ) . Competition injuries accounted for 50.4 % of the total , with 36 % of these occurring in the last third of each half . Strains ( 31 % ) and sprains ( 20 % ) were the main injury types , predominantly affecting the lower limb , with a similar proportion of injuries affecting the thigh ( 19 % ) , ankle ( 19 % ) , and knee ( 18 % ) . Growth related conditions , including Sever ’s disease and Osgood-Schlatter ’s disease , accounted for 5 % of total injuries , peaking in the under 13 age group for Osgood-Schlatter ’s disease and the under 11 age group for Sever ’s disease . The rate of re-injury of exactly the same anatomical structure was 3 % . Conclusions : Footballers are at high risk of injury and there is a need to investigate ways of reducing this risk . Injury incidence at academy level is approximately half that of the professional game . Academy players probably have much less exposure to injury than their full time counterparts . Areas that warrant further attention include the link between musculoskeletal development and the onset of youth related conditions such as Sever ’s disease and Osgood-Schlatter ’s disease , the significant number of non-contact injuries that occur in academy football , and the increased rates of injury during preseason training and after the mid season break . This study has highlighted the nature and severity of injuries that occur at academy level , and the third part of the audit process now needs to be undertaken : the implementation of strategies to reduce the number of injuries encountered at this level The purpose of this study was to register prospect ively the injuries in female soccer and to study their correlation to potential risk factors . A total of 123 senior players from eight teams of different levels were followed during one season . Isokinetic knee muscle strength at 60 and 180 degrees/s , one-leg-hop , vertical jump , square-hop , and continuous multistage fitness test ( MFT ) were tested at the end of the pre-season . In addition , Body Mass Index ( BMI ) and general joint laxity were measured . During the season , April-October , all injuries result ing in absence from one practice /game or more were registered . Forty-seven of the 123 players sustained altogether 65 injuries . The total injury rate was 14.3 per 1000 game hours and 3.7 per 1000 practice hours . The knee ( 26 % ) was the most commonly injured region followed by the foot ( 12 % ) , ankle ( 11 % ) , thigh ( 11 % ) and back ( 11 % ) . The risk of sustaining moderate and major injuries increased in the later part of the game or practice . Significant risk factors for injuries were an increased general joint laxity ( odds ratio (OR)=5.3 , P<0.001 ) , a high performance in the functional test square-hop ( OR=4.3 , P=0.002 ) , and an age over 25 years ( OR=3.7 , P=0.01 ) . The injury rate was not different compared to male soccer , but knee injuries were more common , which is in accordance with previous studies . None of the risk factors identified in this study is easily applicable for future intervention studies in the attempts to reduce the injury rate in female soccer Abstract The warm-up programme “ FIFA 11 + ” has been shown to reduce football injuries in different population s , but so far veteran players have not been investigated . Due to differences in age , skill level and gender , a simple transfer of these results to veteran football is not recommended . The purpose of this study was to investigate the preventive effects of the “ FIFA 11 + ” in veteran football players . Twenty veteran football teams were recruited for a prospect i ve 9-month ( 1 season ) cluster-r and omised trial . The intervention group ( INT , n = 146 ; 45 ± 8 years ) performed the “ FIFA 11 + ” at the beginning of each training session , while the control group ( CON , n = 119 ; 43 ± 6 years ) followed its regular training routine . Player exposure hours and injuries were recorded according to an international consensus statement . No significant difference was found between INT and CON in overall injury incidence ( incidence rate ratio [ IRR ] : 0.91 [ 0.64–1.48 ] ; P = 0.89 ) . Only severe injuries reached statistical significance with higher incidence in CON ( IRR : 0.46 [ 0.21–0.97 ] , P = 0.04 ) . Regular conduction ( i.e. once a week ) of the “ FIFA 11 + ” did not prevent injuries in veteran footballers under real training and competition circumstances . The lack of preventive effects is likely due to the too low overall frequency of training sessions |
11,146 | 28,877,081 | Discussion : WM is usually better tolerated than CBM but has more technical problems . | Introduction : The primary aim of this systematic review was to determine the safety , technical efficacy , and effectiveness of 48-hour wireless pH monitoring ( WM ) for gastroesophageal reflux disease ( GERD ) , compared with no pH monitoring in patients who failed to tolerate a catheter .
In the absence of eligible studies , the secondary aim was to determine these performance characteristics for WM relative to catheter-based pH monitoring ( CBM ) in patients suspected of GERD , who are able to tolerate a catheter . | CONTEXT Esophageal pH monitoring is considered to be the gold st and ard for the diagnosis of gastroesophageal acid reflux . However , this method is very troublesome and considerably limits the patient 's routine activities . Wireless pH monitoring was developed to avoid these restrictions . OBJECTIVE To compare the first 24 hours of the conventional and wireless pH monitoring , positioned 3 cm above the lower esophageal sphincter , in relation to : the occurrence of relevant technical failures , the ability to detect reflux and the ability to correlate the clinical symptoms to reflux . METHODS Twenty-five patients referred for esophageal pH monitoring and with typical symptoms of gastroesophageal reflux disease were studied prospect ively , underwent clinical interview , endoscopy , esophageal manometry and were su bmi tted , with a simultaneous initial period , to 24-hour catheter pH monitoring and 48-hour wireless pH monitoring . RESULTS Early capsule detachment occurred in one ( 4 % ) case and there were no technical failures with the catheter pH monitoring ( P = 0.463 ) . Percentages of reflux time ( total , upright and supine ) were higher with the wireless pH monitoring ( P < 0.05 ) . Pathological gastroesophageal reflux occurred in 16 ( 64 % ) patients su bmi tted to catheter and in 19 ( 76 % ) to the capsule ( P = 0.355 ) . The symptom index was positive in 12 ( 48 % ) patients with catheter pH monitoring and in 13 ( 52 % ) with wireless pH monitoring ( P = 0.777 ) . CONCLUSIONS 1 ) No significant differences were reported between the two methods of pH monitoring ( capsule vs catheter ) , in regard to relevant technical failures ; 2 ) Wireless pH monitoring detected higher percentages of reflux time than the conventional pH-metry ; 3 ) The two methods of pH monitoring were comparable in diagnosis of pathological gastroesophageal reflux and comparable in correlating the clinical symptoms with the gastroesophageal reflux Background Wireless capsule pH-metry ( WC ) is better tolerated than st and ard nasal pH catheter ( SC ) , but endoscopic placement is expensive . Aims : to confirm that non-endoscopic peroral manometric placement of WC is as effective and better tolerated than SC and to perform a cost analysis of the available esophageal pH-metry methods . Methods R and omized trial at 2 centers . Patients referred for esophageal pH testing were r and omly assigned to WC with unse date d peroral placement or SC after esophageal manometry ( ESM ) . Primary outcome was overall discomfort with pH-metry . Costs of 3 different pH-metry strategies were analyzed : 1 ) ESM + SC , 2 ) ESM + WC and 3 ) endoscopically placed WC ( EGD + WC ) using publicly funded health care system perspective . Results 86 patients ( mean age 51 ± 2 years , 71 % female ) were enrolled . Overall discomfort score was less in WC than in SC patients ( 26 ± 4 mm vs 39 ± 4 mm VAS , respectively , p = 0.012 ) but there were no significant group differences in throat , chest , or overall discomfort during placement . Overall failure rate was 7 % in the SC group vs 12 % in the WC group ( p = 0.71 ) . Per patient costs ( $ Canadian ) were $ 1475 for EGD + WC , $ 1014 for ESM + WC , and $ 906 for ESM + SC . Decreasing the failure rate of ESM + WC from 12 % to 5 % decreased the cost of ESM + WC to $ 991 . The ESM + SC and ESM + WC strategies became equivalent when the cost of the WC device was dropped from $ 292 to $ 193 . Conclusions Unse date d peroral WC insertion is better tolerated than SC pH-metry both overall and during placement . Although WC is more costly , the extra expense is partially offset when the higher patient and caregiver time costs of SC are considered . Trial registration Clinical trials.gov Identifier Objectives Oesophageal pH monitoring is the current st and ard for the diagnosis of gastro-oesophageal reflux disease . The Bravo capsule allows 48-h monitoring without the need for a naso-oesophageal catheter . Our aim was to assess the Bravo capsule in terms of patient discomfort and interference with daily activities , and to determine if 48-h Bravo pH studies facilitate the diagnosis of gastro-oesophageal reflux disease . Methods Ambulatory pH studies were performed at two hospitals using either the Bravo capsule ( n=100 ) or a conventional naso-oesophageal catheter ( n=100 ) . Participants were selected either for investigation of symptoms suggestive of gastro-oesophageal reflux disease , or to follow-up antireflux surgery . All participants completed question naires to assess discomfort and interference with daily activities . Results Eighty-nine Bravo studies recorded at least 48 h of data , and 95 were diagnostic . Bravo participants reported significantly less discomfort during insertion ( P<0.0001 ) and monitoring ( P<0.0001 ) , and less interference with daily activities ( P<0.0001 ) , eating ( P<0.005 ) , sleeping ( P<0.0001 ) and work ( P<0.0001 ) . No significant difference was observed between day 1 and 2 median total time pH<4 ( 4.0 and 4.3 % , P=0.64 ) , erect time pH<4 ( 5.0 and 5.0 % , P=0.56 ) , supine time pH<4 ( 0.5 and 0.5 % , P=0.23 ) , and Johnson – DeMeester scores ( 15.9 and 16.2 , P=0.90 ) . Ten Bravo participants ( 10 % ) were diagnosed with gastro-oesophageal reflux disease using day 2 data after a normal day 1 . Conclusions The Bravo capsule significantly reduces the patient discomfort and interference with normal daily activities during pH monitoring associated with a naso-oesophageal catheter . Moreover , 48-h Bravo studies offer an advantage over conventional 24-h studies in diagnosing gastro-oesophageal reflux 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 : The wireless pH is a new technique to monitor oesophageal acid exposure Goals To prospect ively evaluate the tolerability and clinical utility of the Bravo pH capsule in children . Background Acid reflux is common in children , and pH testing can be used to correlate acid exposure with symptom expression . The tolerability and clinical utility of the Bravo capsule in children has not been prospect ively evaluated . Methods This was a prospect i ve , open-label trial conducted at an academic medical center . Patient demographics , symptoms , and medication use were recorded in an outpatient setting . After Bravo capsule placement , patients were followed to determine whether the results of the Bravo capsule study changed clinical management . Results Fifty children ( mean±SD=13±3 y ; 52 % female ) were studied ; no complications occurred . Reflux symptoms ( 40 % ) , abdominal pain ( 18 % ) , and nausea/vomiting ( 14 % ) were the 3 most common symptoms leading to Bravo capsule placement . Nearly all studies ( 96 % ) were performed off acid-suppressing medications . Results of the Bravo pH study changed clinical care in 88 % of children ; management changed more frequently in children with an abnormal study ( 94 % ) versus those with a normal study ( 78 % ; P<0.0001 ) . Conclusions The Bravo pH capsule is a safe , well-tolerated test to evaluate acid reflux symptoms in children , and the data obtained frequently changes patient management OBJECTIVES : Ambulatory esophageal pH monitoring has limited diagnostic accuracy in patients with gastroesophageal reflux disease ( GERD ) , especially in those with non-erosive reflux disease ( NERD ) . In addition , there is lack of symptom – reflux association in the majority of GERD patients . The aim of this study was to evaluate the impact of measuring acid exposure 1 cm above the gastroesophageal junction ( GEJ ) on diagnostic accuracy and symptom correlation in GERD patients compared with conventional pH measurements ( 6 cm above the GEJ ) using the wireless pH system . METHODS : GERD patients and controls as defined by two vali date d question naires ( Gastroesophageal Reflux Question naire and Reflux Disease Question naire ) were prospect ively enrolled . Under direct endoscopic vision , two wireless pH capsules ( BRAVO , Given Imaging , Yokneam , Israel ) were placed 6 and 1 cm , respectively , above the GEJ . Receiver operator characteristic curves were constructed , and symptom indexes were calculated separately for pH measurements at 6-cm ( proximal ) and 1-cm ( distal ) locations . RESULTS : A total of 40 GERD patients ( 20 erosive esophagitis ( EE ) and 20 NERD ) and 16 controls were analyzed . Sensitivity and specificity of abnormal acid exposure times in GERD were as follows : proximal : 67 and 66 % , distal : 60 and 88 % ; in EE proximal : 75 and 81 % , distal : 84 and 92 % ; and in NERD proximal : 61 and 67 % , distal : 58 and 66 % , respectively . The proportion of patients with a positive symptom – reflux correlation in GERD was as follows : symptom index ( SI ) : proximal : 35 % , distal : 50 % ; symptom sensitivity index ( SSI ) : proximal : 25 % , distal : 5 % ; and symptom-associated probability ( SAP ) : proximal : 30 % and distal : 35 % . The higher proportion of patients with a positive SI distally was due to the EE group ( EE , proximal : 35 % and distal : 65 % ; NERD , proximal : 35 % and distal : 35 % ) . CONCLUSIONS : Compared with the traditional location , measurement of acid reflux 1 cm above the GEJ improved the diagnostic accuracy as well as symptom correlation in EE , but not in NERD patients . Thus , pH monitoring 1 cm above the GEJ for improving the diagnosis of NERD can not be recommended in clinical practice at this time OBJECTIVES : Esophageal pH monitoring using a wireless pH capsule has been suggested to generate less adverse symptoms result ing in improved patient acceptance compared with the catheter-based method although evidence to support this assumption is lacking . The aim of this study was to evaluate and compare the subjective experience of patients undergoing both techniques for esophageal pH monitoring . METHODS : Using a r and omized study design , patients referred for esophageal pH testing underwent both wireless and traditional catheter-based 24-h pH recording with a 7-day interval . The wireless pH capsule was placed during endoscopy and followed by 48-h pH recording . All patients answered a question naire , including a 10-cm visual analog scale ( VAS ) , which described the perceived severity of symptoms and the degree of interference with normal daily activities during the pH tests . RESULTS : Thirty-one patients , 16 women and 15 men , were included in the analysis . The severity of all adverse symptoms associated with the wireless technique was significantly lower compared with the catheter-based technique ( median VAS 2.1 vs 5.1 , P < 0.001 ) . Wireless pH recording was associated with less interference with off-work activities and normal daily life , median VAS 0.6 and 0.7 compared with 5.0 and 5.7 , respectively , for the catheter-based technique ( P < 0.0001 ) . Patients actively working during both tests reported less interference with normal work during the capsule-based test than during the catheter-based pH test ( median VAS 0.3 vs 6.8 , P = 0.005 ) . Twenty-seven patients ( 87 % ) stated that , if they had to undergo esophageal pH monitoring again , they preferred the wireless test over the catheter-based pH test ( P < 0.0001 ) . CONCLUSIONS : This r and omized study showed that a significant majority of patients undergoing esophageal pH monitoring preferred the wireless pH capsule over the traditional catheter-based technique because of less adverse symptoms and less interference with normal daily life Background Currently , pH monitoring is the gold st and ard for assessing esophageal acid exposure in patients with gastroesophageal reflux disease ( GERD ) . The shortcomings of 24-h pH-monitoring wires led to the development of a 48-h , catheter-free pH measurement system using the telemetry technique with the BRAVO capsule . This prospect i ve study aim ed to compare conventional 24-h pH monitoring with the BRAVO catheter-free pH-monitoring system in patients with GERD , patients after antireflux surgery , and a healthy control group . Methods A sample of 133 participants were enrolled in the current trial and divided into three subgroups . Group 1 consisted of 10 healthy volunteers . Group 2 consisted of 123 patients with symptomatic gastroesophageal reflux and endoscopic signs of esophagitis . Group 3 consisted of 43 GERD patients ( extracted from group 2 ) who underwent a laparoscopic 360 ° “ floppy ” Nissen fundoplication . All the patients underwent both conventional 24-h pH monitoring and BRAVO catheter-free pH monitoring . The data for both methods were recorded and compared in line with the different patient groups regarding their validity and reliability . Additionally , all the patients were interviewed with a st and ardized question naire concerning their subjective perception of the two different methods . Results Both the 24-h pH monitoring and the 48-h BRAVO catheter-free pH monitoring could be successfully performed for all the patients . During measurement , 122 of the patients ( 92 % ) continued working or performing daily activities . A significant difference could not be found regarding objective outcome between the two measurement methods in the three patient groups . The two methods showed comparable results in terms of data and measurement reliability . The validity also was comparable , with no significant differences within the groups . Concerning the patients ’ subjective estimation of the two methods , the patients reported reduced regular activities and a higher level of discomfort during measurement with the conventional 24-h pH-monitoring system ( p < 0.001 and p < 0.0001 , respectively ) . Conclusion Both conventional 24-h pH monitoring and the 48-h catheter-free pH monitoring are valid and reliable recording devices for measuring esophageal acid exposure . However , from the patients ’ point of view , the BRAVO capsule affords less discomfort in the throat and allows more normal daily activities Goal The aim of this prospect i ve study was to determine whether this test changes patient diagnosis , provides new information , or alters patient care . Background The wireless pH capsule is widely used to evaluate symptoms of acid reflux , although the clinical utility of this test is unknown . Study Before pH capsule placement , referring providers completed a question naire requesting indications for the test , symptoms , prior testing , and medication use . A follow-up survey determined whether providers believed that results of the wireless pH test provided new information , changed patient diagnosis or altered patient management . Results During a 14-month period , 598 wireless pH capsule studies were conducted ; 490 patients were eligible for inclusion , and 309 question naires were returned ( 63 % ) . Mean patient age=48 ( ±15 y ) . The most common symptom leading to pH capsule placement was acid reflux ( heartburn/regurgitation ; 62 % ) , followed by chest pain ( 11 % ) . Wireless pH capsule results provided new information in 88 % of patients , changed the diagnosis in 22 % , and altered management in 63 % . Conclusions This study shows the clinical utility of the wireless pH capsule , with test results frequently providing new information , altering patient management or changing patient diagnoses . Future studies should define specific test characteristics most likely to influence patient care AIM To investigate the feasibility and safety of pH capsule to monitor pH in patients with gastroesophageal reflux disease ( GERD ) . METHODS Ninety-one patients with symptoms suggestive of GERD were enrolled in this study , 46 of whom were r and omized to the pH capsule group ; the remaining 45 patients used the conventional catheter and pH capsule simultaneously . The pH data and traces were recorded via automatic analysis , and capsule detachment was assessed using X-ray images . All of the patients were required to complete a question naire regarding tolerance with the capsule . RESULTS The capsules were successfully attached on the first attempt , and no early detachment of the capsules was observed . Compared to the 24-h pH data recorded with the conventional catheter , the data collected with the pH capsule showed no significant differences in 24-h esophageal acid exposure . The measurements of esophageal acid exposure over 24 h collected with the two devices showed a significant correlation ( r(2 ) = 0.996 , P < 0.001 ) . Capsule detachment occurred spontaneously in 89 patients , and 2 capsules required endoscopic removal due to chest pain . The capsule was associated with less interference with daily activity . CONCLUSION The wireless pH capsule provides a feasible and safe method for monitoring gastroesophageal reflux and therefore may serve as an important tool for diagnosing GERD Objective Wireless pH monitoring is currently employed in the distal esophagus . There are no controlled studies on the feasibility/safety of proximal esophageal wireless pH capsule placement . We tested the hypothesis that there will be no difference in patient perception of a more proximally placed pH capsule . Study Design R and omized single-blinded sham-controlled trial . Setting Tertiary care center . Subjects and Methods All patients had a wireless pH capsule positioned 6 cm proximal to the gastroesophageal junction . They were r and omized into intervention or sham groups after distal capsule placement . The delivery introducer was positioned 10 cm proximal to the distal esophageal capsule , and a second capsule was either deployed ( intervention ) or not ( sham ) based on group allocation . Patients were blinded to group assignment . Modified Edmonton Score was used to assess for chest pain , dysphagia , and odynophagia . The primary endpoints were ( 1 ) required endoscopic removal because of discomfort and ( 2 ) change in chest pain scores , controlling for baseline pain . Results Patients were r and omized to either the intervention , proximal esophageal capsule ( n = 11 ) , or sham ( n = 11 ) . Patients with proximal pH probes had higher odds of having their chest pain ( odds ratio [ OR ] , 8.44 ; 95 % confidence interval [ CI ] , 1.35 - 52.6 ; P = .02 ) , odynophagia ( OR , 49.5 ; 95 % CI , 4.70 - 520 ; P = .001 ) , and dysphagia ( OR , 14.3 ; 95 % CI , 2.12 - 96.6 ; P = .006 ) exacerbated . Two ( 2/11 ; 18 % ) proximally deployed probes required endoscopic removal because of patient intolerance or discomfort . Conclusion A proximal esophageal wireless pH monitor placement is feasible but results in increased chest pain , odynophagia , and dysphagia that can be severe enough to require endoscopic removal . These limitations preclude its potential clinical benefit |
11,147 | 31,496,742 | There were no significant differences between MWA and RFA for other efficacy and safety outcomes .
Higher frequency ( 2450 MHz ) and larger tumor size ( ≥2.5 cm ) are amongst variables that may be associated with improved outcomes for MWA .
Conclusion MWA is at least as safe and effective as RFA for treating liver cancer and demonstrated significantly reduced LTP rates . | Purpose Percutaneous ablation techniques , including microwave ablation ( MWA ) and radiofrequency ablation ( RFA ) , have become important minimally invasive treatment options for liver cancer .
This systematic review compared MWA with RFA for treatment of liver cancer . | Abstract Background Hepatocellular carcinoma ( HCC ) is a primary tumor of the liver with poor prognosis . For early stage HCC , treatment options include surgical resection , liver transplantation , and percutaneous ablation . Percutaneous ablative techniques ( radiofrequency and microwave techniques ) emerged as best therapeutic options for nonsurgical patients . Aims We aim ed to determine the safety and efficacy of radiofrequency and microwave procedures for ablation of early stage HCC lesions and prospect ively follow up our patients for survival analysis . Patients and methods One Hundred and 11 patients with early HCC are managed in our multidisciplinary clinic using either radiofrequency or microwave ablation . Patients are assessed for efficacy and safety . Complete ablation rate , local recurrence , and overall survival analysis are compared between both procedures . Results Radiofrequency ablation group ( n = 45 ) and microwave ablation group ( n = 66 ) were nearly comparable as regards the tumor and patients characteristics . Complete ablation was achieved in 94.2 and 96.1 % of patients managed by radiofrequency and microwave ablation techniques , respectively ( p value 0.6 ) with a low rate of minor complications ( 11.1 and 3.2 , respectively ) including subcapsular hematoma , thigh burn , abdominal wall skin burn , and pleural effusion . Ablation rates did not differ between ablated lesions ≤3 and 3–5 cm . A lower incidence of local recurrence was observed in microwave group ( 3.9 vs. 13.5 % in radiofrequency group , p value 0.04 ) . No difference between both groups as regards de novo lesions , portal vein thrombosis , and abdominal lymphadenopathy . The overall actuarial probability of survival was 91.6 % at 1 year and 86.1 % at 2 years with a higher survival rates noticed in microwave group but still without significant difference ( p value 0.49 ) . Conclusion Radiofrequency and microwave ablations led to safe and equivalent ablation and survival rates ( with superiority for microwave ablation as regards the incidence of local recurrence ) AIM To retrospectively compare the initial response , local recurrence , and complication rates of radiofrequency ablation ( RFA ) vs microwave ablation ( MWA ) when combined with neoadjuvant bl and transarterial embolization ( TAE ) or drug-eluting microsphere chemoembolization ( TACE ) for the treatment of hepatocellular carcinoma ( HCC ) . METHODS A total of 35 subjects with Barcelona Clinic Liver Cancer ( BCLC ) very early and early-stage HCC ( range : 1.2 - 4.1 cm ) underwent TAE ( 23 ) or TACE ( 12 ) with RFA ( 15 ) or microwave ablation ( MWA ) ( 20 ) from January 2009 to June 2015 as either definitive therapy or a bridge to transplant . TAE and TACE were performed with 40 - 400μm particles and 30 - 100μm plus either doxorubicin- or epirubicin-eluting microspheres , respectively . Initial response and local progression were evaluated using modified response evaluation criteria in solid tumors . Complications were grade d using common terminology criteria for adverse events version 5.0 . RESULTS Complete response rates were 80 % ( 12/15 ) for RFA + TAE/TACE and 95 % ( 19/20 ) for MWA + TAE/TACE ( P = 0.29 ) . Local recurrence rate was 30 % ( 4/12 ) for RFA + TAE/TACE and 0 % ( 0/19 ) for MWA + TAE/TACE . Durability of response , defined as local disease control for duration of the study , demonstrated a significant difference in favor of MWA ( P = 0.0091 ) . There was no statistical difference in complication rates ( 3 vs 2 ) . CONCLUSIONS MWA and RFA when combined with neoadjuvant TAE or TACE have similar safety and efficacy in the treatment of early-stage HCC . MWA provided more durable disease control in this study ; however , prospect i ve data remain necessary to evaluate superiority of either modality Purpose To compare MWA and RFA combined with TACE for HCC nodules exceeding 3 cm . Methods 19 lesions su bmi tted to MWA ( G1 ) were retrospectively compared with a combined treatment group ( G2 ) matching by tumor characteristics ( mean size 43 and 45 mm in G1 and G2 , respectively ) . Technical success , complications , complete ablation ( CA ) , and maintained CA ( mCA ) were evaluated . Results Technical success was achieved in all cases . Overall mortality was zero , both in G1 and G2 . No significant differences were found in complications rates ( 3 in G1 and 2 in G2 ) . CA was obtained in 11 ( 58 % ) HCC in G1 and 15 ( 79 % ) in G2 ( p = n.s . ) . CA was obtained in 75.5 % ( G1 ) and 89 % ( G2 ) nodules up to 4 cm , 45 % and 70 % nodules > 4 cm , respectively . At statistical analysis , size result ed as predictor for CA only in G1 ( mean diameter of CA vs non-CA 39.9 vs. 47.7 mm , p = 0.021 ) . During follow-up ( 13.1 and 14.4 months in G1 and G2 ) , mCA occurred in 6/19 ( 32 % ) nodules in G1 , 8/19 ( 42 % ) in G2 . Conclusion MWA and combined therapy are comparable as for safety . No significant differences were found in terms of technique effectiveness . Larger r and omized studies should be design ed to confirm MWA as a valid alternative to combined therapy Background and aim The risk of local tumour progression ( LTP ) and factors predicting LTP following percutaneous thermal ablation ( PTA ) of early-stage hepatocellular carcinoma ( HCC ) have not been well studied in non-trial setting s and may be underestimated . We aim ed to assess these outcomes in a multicentre study . Patients and methods This was a retrospective review of consecutive patients with early-stage HCC treated with a curative intent across three tertiary Australian centres between 2006 and 2012 with either radiofrequency ablation or microwave ablation . The primary endpoint was LTP and multivariate analysis was carried out to identify the independent predictors of LTP . Results In total 145 HCC nodules were treated in 126 patients ( 78 % men , mean±SD age 62±10 years ) with a mean±SD follow-up of 13.5±13 months . Local recurrence was observed in 23.4 % ( 34/145 ) . Mean±SD LTP-free survival was 46.9±3.6 months . For HCC nodules 2 cm or less , local recurrence rates were lower ( 15.9 % ) , with a mean±SD LTP-free survival of 48.8±4.2 months . Poorly differentiated HCC [ hazard ratio ( 95 % confidence interval)=4.8 ( 1.1–20.4 ) , P=0.032 ] and pretreatment & agr;-fetoprotein more than 50 kIU/l [ 8.2 ( 1.7–39.0 ) , P=0.008 ] were independent predictors of LTP . LTP rates were not significantly different between the radiofrequency ablation and the microwave ablation groups ( 22.8 vs. 25.8 % , P=0.7 ) . There were six ( 4.8 % ) procedure-related adverse events , but no deaths . Conclusion Local recurrence after PTA for early-stage HCC is high in routine clinical practice . Poorly differentiated HCC and pretreatment & agr;-fetoprotein are important , independent predictors of LTP . Further well- design ed r and omized controlled trials with larger sample sizes using adjuvant therapies in combination with PTA to decrease LTP rates are warranted Purpose To compare the ablation area produced by a single application of a microwave ablation ( MWA ) system , equipped with a miniaturized device on the tip of the antenna entrapping reflected microwaves , with that produced by an internally cooled radiofrequency ablation ( RFA ) system . Material s and Methods Forty patients with primary or secondary inoperable liver tumors , selected to undergo percutaneous thermal ablation , were r and omly assigned to MWA or RFA procedure . The ablation areas produced by a single application of MWA ( ablation time 10 min ) or RFA ( ablation time 12 min ) energy were assessed by contrast-enhanced ultrasonography immediately after the end of the procedure . The long- and short-axis diameters of the ablation areas were measured and compared using Student t test . Results Long- and short-axis diameters of the ablation areas produced by MWA were significantly greater than those produced by RFA : 48.5 ± 6.7 versus 30.9 ± 1.1 mm ( p < 0.0001 ) and 38.5 ± 4.6 versus 26.8 ± 2.9 mm ( p < 0.0001 ) , respectively . Conclusion The MWA system can achieve significantly larger ablation areas than the internally cooled RFA system . Broader r and omized trials are strongly warranted to investigate whether such superiority can translate into better long-term outcome of the ablation procedure Abstract Objective To prospect ively compare microwave ( MW ) ablation using a modified internal cooled-shaft antenna with radiofrequency ( RF ) ablation in in vivo porcine liver and in patients with small hepatocellular carcinoma ( sHCC ) . Methods In an animal study , MW and RF ablations using a cooled-shaft antenna or internally cooled electrode were performed in in vivo porcine liver . Coagulation diameters of both ablations were compared . For clinical study , 42 patients with sHCC were treated with MW or RF ablation . Complete ablation ( CA ) and local tumour progression ( LTP ) were compared . Results MW ablation produced significantly larger ablation zones than RF ablation in both porcine liver and sHCC with an ablated volume of 33.3 ± 15.6 cm3 vs. 18.9 ± 9.1 cm3 and 109.3 ± 58.3 cm3 vs. 48.7 ± 30.5 cm3 , respectively . The CA rate was 95.5 % ( 21/22 ) for MW ablation and 95.0 % ( 19/20 ) for RF ablation . In a 5.1-month follow-up , the LTP rate was 18.2 % ( 4/22 ) in the MW ablation group and 15.0 % ( 3/20 ) in the RF ablation group . Conclusion MW ablation using a modified cooled-shaft antenna produces a larger ablation zone than RF ablation , with an efficacy similar to RF ablation in local tumour control . MW ablation is a safe and promising treatment of sHCC.Key Points• Microwave ablation with a cooled-shaft antenna produces a larger ablation zone than radiofrequency ablation . • Microwave and radiofrequency ablation showed similar local tumour control in small HCC . • Microwave ablation seems safe and efficient for small liver cancers ( <3 cm ) Purpose : To compare the effectiveness of ultrasound (US)-guided percutaneous 915 MHz microwave ( MW ) ablation with the 2450 MHz MW ablation for large hepatocellular carcinoma ( HCC ) ( > 4 cm in diameter ) . Material s and methods : Patients with HCC > 4 cm in diameter who underwent US-guided percutaneous MW ablation with curative intention between March 2007 and December 2008 ( 39 ) were r and omly divided into two groups , 915 MHz MW group and 2450 MHz MW group . We compared the results of ablation between the two groups . Results : Fewer antenna insertions for each tumour were required in the 915 MHz MW group ( 3.69 ± 0.6 ) than in the 2450 MHz MW group ( 4.71 ± 1.61 ) ( p = 0.01 ) . According to the follow-up contrast-enhanced imagings , technique effectiveness rate was 85.7 % ( 18/21 ) and 73.7 % ( 14/19 ) in the 915 MHz MW group and 2450 MHz MW group , respectively ( p = 0.44 ) . The rate of local tumour progression ( LTP ) was 14.3 % ( 3/21 ) and 26.3 % ( 5/19 ) in the 915 MHz MW group and 2450 MHz MW group , respectively ( p = 0.44 ) . There were no deaths and no thrombosis of major vessels in any patient . Conclusions : Compared with 2450 MHz MW ablation , our initial experience showed that percutaneous 915 MHz MW ablation with cooled-shaft antennae was safe and could achieve a high technique effectiveness rate with fewer insertion numbers in the treatment of large HCC . Therefore , percutaneous 915 MHz MW ablation may provide a new method for the treatment of large HCC OBJECTIVES There are no prospect i ve studies of laparoscopic microwave ( MW ) ablation in patients with hepatocellular carcinoma ( HCC ) . The aim of this study was to demonstrate the safety and efficacy of laparoscopic MW ablation . METHODS A prospect i ve study group of consecutive HCC patients considered ineligible for liver resection and /or percutaneous ablation was conducted from December 2009 to December 2010 . Short-term ( 3-month ) outcomes included a central ized revision of radiological response , mortality and morbidity . Mid-term ( 24-month ) outcomes included time to recurrence in the study group compared with that in a cohort of consecutive patients treated with laparoscopic radiofrequency ( RF ) ablation using propensity score analysis . RESULTS A total of 42 patients were enrolled . Their median age was 64 years ; 67 % were positive for hepatitis C virus ; 33 % were of Child-Pugh class B status ; the median tumour diameter was 2.5 cm , and 48 % of patients had multinodular HCC . In 47 of 50 ( 94 % ) nodules treated with MW ablation , a complete radiological response was observed at 3 months . There was no perioperative mortality . The overall morbidity rate was 24 % . The 2-year survival rate was 79 % and the 2-year recurrence rate was 55 % . Using propensity score analysis ( in 28 MW ablation patients and 28 RF ablation controls ) , 2-year recurrence rates were 55 % in the MW ablation group and 77 % in the control group ( P = 0.03 ) . CONCLUSIONS Laparoscopic MW ablation is a safe and effective therapeutic option for selected HCC patients who are ineligible for liver resection and /or percutaneous ablation Background . The authors have used percutaneous microwave coagulation therapy ( PMCT ) as a new percutaneous local treatment for single unresectable hepatocellular carcinoma ( HCC ) measuring 2 cm or less in greatest dimension ( small HCC ) . PMCT was used to attempt a cure of the disease . In this study , the efficacy of this treatment was assessed The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma ( HCC ) [ 1 ] . Liver cancer represents the sixth most common cancer in the world ( 749 000 new cases ) and the third cause of cancer-related death ( 692 000 cases ) . The incidence varies from 3 out of 100 000 in Western countries , to more than 15 out of 100 000 in certain areas of the world , mapping the geographical distribution of viral hepatitis B ( HBV ) and hepatitis C ( HCV ) , the most important causes of chronic liver disease and HCC [ 2 ] . Most cases arise in those regions with limited re sources . The incidence of HCC increases progressively with advancing age in all population s , with a strong male preponderance . The association of chronic liver disease and HCC represents the basis for preventive strategies , including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [ III , A ] . It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan , given the importance of other risk factors in Europe , such as alcoholic and non-alcoholic fatty liver disease . The control of other risk factors for chronic liver disease and cancer is more difficult to implement , such as cutting down on the consumption of alcohol and programs aim ing at a healthier lifestyle in the light of the obesity p and emic [ 3 , 4 ] . In Africa , reduction of exposure to aflatoxin B1 , especially in HBV-infected individuals , may lower the risk of HCC . HCC may evolve from subclasses of adenomas , and in < 10 % of cases HCC occurs in a normal liver . Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population . The success of surveillance is influenced by the incidence of HCC in the target population , the availability and acceptance of efficient diagnostic tests and the availability of effective treatment . Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [ 5 ] . Surveillance of non-cirrhotic patients is also advocated , especially in HBV carriers with serum viral load > 10 000 copies/ml [ 6 ] or HCVinfected patients with bridging fibrosis ( F3 ) [ III , A ] . Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [ III , A ] . Japanese cohort studies have shown that surveillance by abdominal ultrasound result ed in an average size of the detected tumors of 1.6 ± 0.6 cm , with < 2 % of the cases exceeding 3 cm [ 7 ] . In the Western world and in less experienced centers , sensitivity of finding early-stage HCC by ultrasound is considerably less effective [ 8 ] . There are no data to support the use of contrast-enhanced computed tomography ( CT ) or magnetic resonance imaging ( MRI ) for surveillance . In many centers , ultrasound surveillance is complemented with the determination of serum alphafetoprotein ( AFP ) , which can lead to a 6%–8 % gain in the tumor detection rate but at the price of false-positive results . A r and omized , controlled trial ( RCT ) of Chinese patients with chronic hepatitis B infection compared surveillance ( ultrasound and serum AFP measurements every 6 months ) versus no surveillance [ 9 ] . Despite low compliance with the surveillance program ( 55 % ) , HCC-related mortality was reduced by 37 % in the surveillance arm . Considering the most appropriate surveillance interval , a r and omized study comparing a 3versus 6-month based schedule failed to detect any differences [ 10 ] . Therefore , surveillance of patients at risk for HCC should be carried out by abdominal ultrasound every 6 months [ I , A ] |
11,148 | 22,419,316 | Non-invasive ventilation can reduce the risk of death in the ICU , endotracheal intubation , shorten ICU stay and length of intubation .
However , the review indicates that non-invasive ventilation may be more beneficial than st and ard oxygen supplementation via a Venturi mask for pneumonia | BACKGROUND Oxygen therapy is widely used in the treatment of lung diseases .
However , the effectiveness of oxygen therapy as a treatment for pneumonia is not well known .
OBJECTIVES To determine the effectiveness and safety of oxygen therapy in the treatment of pneumonia in adults older than 18 years . | Background : In the assessment of severity in community acquired pneumonia ( CAP ) , the modified British Thoracic Society ( mBTS ) rule identifies patients with severe pneumonia but not patients who might be suitable for home management . A multicentre study was conducted to derive and vali date a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups . Methods : Data from three prospect i ve studies of CAP conducted in the UK , New Zeal and , and the Netherl and s were combined . A derivation cohort comprising 80 % of the data was used to develop the model . Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure . The final model was tested against the validation cohort . Results : 1068 patients were studied ( mean age 64 years , 51.5 % male , 30 day mortality 9 % ) . Age ⩾65 years ( OR 3.5 , 95 % CI 1.6 to 8.0 ) and albumin < 30 g/dl ( OR 4.7 , 95 % CI 2.5 to 8.7 ) were independently associated with mortality over and above the mBTS rule ( OR 5.2 , 95 % CI 2.7 to 10 ) . A six point score , one point for each of Confusion , Urea > 7 mmol/l , Respiratory rate ⩾30/min , low systolic(<90 mm Hg ) or diastolic ( ⩽60 mm Hg ) Blood pressure ) , age ⩾65 years ( CURB-65 score ) based on information available at initial hospital assessment , enabled patients to be stratified according to increasing risk of mortality : score 0 , 0.7 % ; score 1 , 3.2 % ; score 2 , 3 % ; score 3 , 17 % ; score 4 , 41.5 % and score 5 , 57 % . The validation cohort confirmed a similar pattern . Conclusions : A simple six point score based on confusion , urea , respiratory rate , blood pressure , and age can be used to stratify patients with CAP into different management groups CONTEXT Continuous positive airway pressure ( CPAP ) is widely used in the belief that it may reduce the need for intubation and mechanical ventilation in patients with acute hypoxemic respiratory insufficiency . OBJECTIVE To compare the physiologic effects and the clinical efficacy of CPAP vs st and ard oxygen therapy in patients with acute hypoxemic , nonhypercapnic respiratory insufficiency . DESIGN , SETTING , AND PATIENTS R and omized , concealed , and unblinded trial of 123 consecutive adult patients who were admitted to 6 intensive care units between September 1997 and January 1999 with a PaO(2)/FIO(2 ) ratio of 300 mm Hg or less due to bilateral pulmonary edema ( n = 102 with acute lung injury and n = 21 with cardiac disease ) . INTERVENTIONS Patients were r and omly assigned to receive oxygen therapy alone ( n = 61 ) or oxygen therapy plus CPAP ( n = 62 ) . MAIN OUTCOME MEASURES Improvement in PaO(2)/FIO(2 ) ratio , rate of endotracheal intubation at any time during the study , adverse events , length of hospital stay , mortality , and duration of ventilatory assistance , compared between the CPAP and st and ard treatment groups . RESULTS Among the CPAP vs st and ard therapy groups , respectively , causes of respiratory failure ( pneumonia , 54 % and 55 % ) , presence of cardiac disease ( 33 % and 35 % ) , severity at admission , and hypoxemia ( median [ 5th-95th percentile ] PaO(2)/FIO(2 ) ratio , 140 [ 59 - 288 ] mm Hg vs 148 [ 62 - 283 ] mm Hg ; P = .43 ) were similarly distributed . After 1 hour of treatment , subjective responses to treatment ( P<.001 ) and median ( 5th-95th percentile ) PaO(2)/FIO(2 ) ratios were greater with CPAP ( 203 [ 45 - 431 ] mm Hg vs 151 [ 73 - 482 ] mm Hg ; P = .02 ) . No further difference in respiratory indices was observed between the groups . Treatment with CPAP failed to reduce the endotracheal intubation rate ( 21 [ 34 % ] vs 24 [ 39 % ] in the st and ard therapy group ; P = .53 ) , hospital mortality ( 19 [ 31 % ] vs 18 [ 30 % ] ; P = .89 ) , or median ( 5th-95th percentile ) intensive care unit length of stay ( 6.5 [ 1 - 57 ] days vs 6.0 [ 1 - 36 ] days ; P = .43 ) . A higher number of adverse events occurred with CPAP treatment ( 18 vs 6 ; P = .01 ) . CONCLUSION In this study , despite early physiologic improvement , CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic , nonhypercapnic respiratory insufficiency primarily due to acute lung injury . JAMA . 2000;284:2352 - 2360 Abstract Objective : To explore three aspects of non-invasive pressure support ventilation ( NIPSV ) applied by face mask to patients with acute respiratory failure ( ARF ) due to severe community-acquired pneumonia ( CAP ) : ( 1 ) the initial acute effects on respiratory rate , gas exchange and hemodynamics , ( 2 ) the clinical course and outcome during ICU and hospital stay , ( 3 ) the nursing workload as measured by the daily PRN 87 ( Project Research in Nursing ) score . Setting : Medical ICU , University Hospital . Design : Prospect i ve , observational study . Patients : Patients without any prior history of chronic lung disease , consecutively admitted to the ICU to receive NIPSV for ARF due to severe CAP . Measurements and results ( means ± SD ) : Twenty-four patients aged 49±17 years , admission APACHE II 13±5 , were included . Admission PaO2/FIO2 , alveolar-arterial oxygen difference ( DA-aO2 ) and PaCO2 were 104±48 , 447±120 and 40±10 mmHg , respectively . All patients were normotensive . During the initial NIPSV trial respiratory rate decreased from 34±8 to 28±10 breaths/min ( p<0.001 ) and arterial oxygenation improved ( PaO2/FIO2 104±48 vs 153±49 , DA-aO2 447±120 vs 370±180 mmHg , p<0.001 ) while PaCO2 remained unchanged . There were no hemodynamic effects . Subsequently , a total of 133 NIPSV trials were performed ( median duration 55 min , range 30–540 min ) over 1–7 days . No complication occurred during NIPSV . Sixteen patients were intubated ( 66 % ) 1.3±1 days after inclusion . Upon inclusion , the patients who were subsequently intubated were older ( 55±15 vs 37±12 years ) and more severely hypoxemic ( 63±11 vs 80±15 mmHg , p<0.05 ) than those not requiring intubation . Eight patients died ( 33 % ) , all in the intubated group . Median lengths of stay in the ICU and hospital were longer in intubated patients ( ICU 16 days , range 3–64 vs 6 days , range 3–7 , p<0.05 ; hospital 23 days , range 9–77 vs 9.5 days , range 4–42 , p<0.05 ) . Mean daily total PRN points were stable throughout the NIPSV period and were not different between the groups . Only 14 % of PRN points result ed from respiratory therapy interventions . PRN score was higher during the first 24 h following intubation than during the first 24 h of NIPSV ( 278±55 vs 228±24 points , p<0.05 ) . Conclusion : Despite initial improvement in arterial oxygenation with NIPSV in patients with ARF due to severe CAP , the intubation rate is high . However , the more favorable outcome and shorter ICU and hospital stays when intubation is avoided , as well as the short delay required to assess the success or failure of NIPSV warrants a trial of NIPSV in this setting . The nursing workload remains stable during NIPSV and does not result predominantly from respiratory therapy interventions OBJECTIVE We have reported previously on the use of noninvasive positive-pressure ventilation ( NPPV ) to assist spontaneous breathing in high-risk hypoxemic patients ( i.e. , PaO(2)/fraction of inspired oxygen [ FIO(2 ) ] ratio , < or = 100 ) who are undergoing diagnostic fiberoptic bronchoscopy ( FOB ) . The efficacy of this intervention in patients with less severe forms of hypoxemia ( i.e. , PaO(2)/FIO(2 ) ratio , < 200 ) is unknown . PATIENTS AND METHODS Twenty-six patients with PaO(2)/FIO(2 ) ratios < or = 200 who required bronchoscopic BAL for suspected nosocomial pneumonia were entered into the study . Thirteen patients were r and omized during FOB to receive NPPV , and 13 patients were r and omized to receive conventional oxygen supplementation by Venturi mask . The primary end points were changes in the PaO(2)/FIO(2 ) ratio during FOB and within 60 min of terminating the procedure . RESULTS AND OUTCOME : At study entry , the two groups were similar in terms of age , simplified acute physiologic score II values , and cardiorespiratory parameters . During FOB , the mean ( + /- SD ) PaO(2)/FIO(2 ) ratio increased by 82 % in the NPPV group ( 261 + /- 100 vs 139 + /- 38 ; p < 0.001 ) and decreased by 10 % in the conventional oxygen supplementation group ( 155 + /- 24 to 139 + /- 38 ; p = 0.23 ) . Sixty minutes after undergoing FOB , the NPPV group had a higher mean PaO(2)/FIO(2 ) ratio ( 176 + /- 62 vs 140 + /- 38 ; p = 0.09 ) , a lower mean heart rate ( 91 + /- 18 vs. 108 + /- 15 beats/min ; p = 0.02 ) , and no reduction in mean arterial pressure in comparison to a 15 % decrease from the baseline in the control group . One patient in the NPPV group and two patients in the control group required nonemergent intubation . Major bacterial isolates included Staphylococcus aureus ( 7 of 30 isolates ; 23 % ) and Pseudomonas aeruginosa ( 12 of 30 isolates ; 40 % ) . CONCLUSION In patients with severe hypoxemia , NPPV is superior to conventional oxygen supplementation in preventing gas-exchange deterioration during FOB with better hemodynamic tolerance Objective : In r and omized studies of heterogeneous patients with hypoxemic acute respiratory failure , noninvasive positive pressure ventilation ( NPPV ) was associated with a significant reduction in endotracheal intubation . The role of NPPV in patients with acute respiratory distress syndrome ( ARDS ) is still unclear . The objective was to investigate the application of NPPV as a first‐line intervention in patients with early ARDS , describing what happens in everyday clinical practice in centers having expertise with NPPV . Design : Prospect i ve , multiple‐center cohort study . Setting : Three European intensive care units having expertise with NPPV . Patients : Between March 2002 and April 2004 , 479 patients with ARDS were admitted to the intensive care units . Three hundred and thirty‐two ARDS patients were already intubated , so 147 were eligible for the study . Interventions : Application of NPPV . Measurements and Main Results : NPPV improved gas exchange and avoided intubation in 79 patients ( 54 % ) . Avoidance of intubation was associated with less ventilator‐associated pneumonia ( 2 % vs. 20 % ; p < .001 ) and a lower intensive care unit mortality rate ( 6 % vs. 53 % ; p < .001 ) . Intubation was more likely in patients who were older ( p = .02 ) , had a higher Simplified Acute Physiology Score ( SAPS ) II ( p < .001 ) , or needed a higher level of positive end‐expiratory pressure ( p = .03 ) and pressure support ventilation ( p = .02 ) . Only SAPS II > 34 and a Pao2/Fio2 ≤175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation . Conclusions : In expert centers , NPPV applied as first‐line intervention in ARDS avoided intubation in 54 % of treated patients . A SAPS II > 34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure A prospect i ve study of 132 patients with severe community-acquired pneumonia ( CAP ) treated in the ICU was carried out to determine the causative agents , the value of the clinical , biological , and radiologic features in predicting the etiology , and to define prognostic factors . The study group included 98 men and 34 women ( mean age : 58 + /- 18 years ) . The most frequent underlying condition was COPD ( 51 patients , 39 percent ) . On admission , 35 patients were in shock , 71 were mentally confused , and 81 ( 61 percent ) required mechanical ventilation during their hospitalization . The clinical , laboratory , and radiologic parameters were of little value for predicting the etiology in patients with severe CAP . An etiologic diagnosis was made in 95 ( 72 percent ) patients . The most frequent pathogens were Streptococcus pneumoniae ( 43 cases [ 45 percent ] ) , Gram-negative bacilli ( 14 cases [ 15 percent ] ) , and Haemophilus influenzae ( 14 cases [ 15 percent ] ) Mortality was 24 percent . It was significantly associated with a age more than 60 years , septic shock , impairment of alertness , mechanical ventilation requirement , bacteremic pneumonia , and S pneumoniae or Enterobacteriaceae as the causes of the pneumonia . Recommendations for antibiotic chemotherapy in patients with severe CAP admitted to the ICU are included CONTEXT Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation ; however , there is considerable variability in the time considered optimal for performing tracheotomy . This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care re sources . OBJECTIVE To determine the effectiveness of early tracheotomy ( after 6 - 8 days of laryngeal intubation ) compared with late tracheotomy ( after 13 - 15 days of laryngeal intubation ) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days . DESIGN , SETTING , AND PATIENTS R and omized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection , who had been ventilated for 24 hours , had a Simplified Acute Physiology Score II between 35 and 65 , and had a sequential organ failure assessment score of 5 or greater . INTERVENTION Patients who had worsening of respiratory conditions , unchanged or worse sequential organ failure assessment score , and no pneumonia 48 hours after inclusion were r and omized to early tracheotomy ( n = 209 ; 145 received tracheotomy ) or late tracheotomy ( n = 210 ; 119 received tracheotomy ) . MAIN OUTCOME MEASURES The primary endpoint was incidence of ventilator-associated pneumonia ; secondary endpoints during the 28 days immediately following r and omization were number of ventilator-free days , number of ICU-free days , and number of patients in each group who were still alive . RESULTS Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group ( 14 % ; 95 % confidence interval [ CI ] , 10%-19 % ) and in 44 patients in the late tracheotomy group ( 21 % ; 95 % CI , 15%-26 % ) ( P = .07 ) . During the 28 days immediately following r and omization , the hazard ratio of developing ventilator-associated pneumonia was 0.66 ( 95 % CI , 0.42 - 1.04 ) , remaining connected to the ventilator was 0.70 ( 95 % CI , 0.56 - 0.87 ) , remaining in the ICU was 0.73 ( 95 % CI , 0.55 - 0.97 ) , and dying was 0.80 ( 95 % CI , 0.56 - 1.15 ) . CONCLUSION Among mechanically ventilated adult ICU patients , early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00262431 Abstract . Context : In patients with hypoxemic acute respiratory failure ( ARF ) , r and omized studies have shown noninvasive positive pressure ventilation ( NPPV ) to be associated with lower rates of endotracheal intubation . In these patients , predictors of NPPV failure are not well characterized . Objective : To investigate variables predictive of NPPV failure in patients with hypoxemic ARF . Design : Prospect i ve , multicenter cohort study . Setting : Eight Intensive Care Units ( ICU ) in Europe and USA . Patients : Of 5,847 patients admitted between October 1996 and December 1998 , 2,770 met criteria for hypoxemic ARF . Of these , 2,416 were already intubated and 354 were eligible for the study . Results : NPPV failed in 30 % ( 108/354 ) of patients . The highest intubation rate was observed in patients with ARDS ( 51 % ) or community-acquired pneumonia ( 50 % ) . The lowest intubation rate was observed in patients with cardiogenic pulmonary edema ( 10 % ) and pulmonary contusion ( 18 % ) . Multivariate analysis identified age > 40 years ( OR 1.72 , 95 % CI 0.92–3.23 ) , a simplified acute physiologic score ( SAPS II ) ≥35 ( OR 1.81 , 95 % CI 1.07–3.06 ) , the presence of ARDS or community-acquired pneumonia ( OR 3.75 , 95 % CI 2.25–6.24 ) , and a PaO2:FiO2 ≤146 after 1 h of NPPV ( OR 2.51 , 95 % CI 1.45–4.35 ) as factors independently associated with failure of NPPV . Patients requiring intubation had a longer duration of ICU stay ( P<0.001 ) , higher rates of ventilator-associated pneumonia and septic complications ( P<0.001 ) , and a higher ICU mortality ( P<0.001 ) . Conclusions : In hypoxemic ARF , NPPV can be successful in selected population s. When patients have a higher severity score , an older age , ARDS or pneumonia , or fail to improve after 1 h of treatment , the risk of failure is higher Abstract Objective . To compare the acute effects of noninvasive pressure support ventilation ( NIPSV ) in non- COPD patients with acute cardiogenic pulmonary edema ( CPE ) and severe community-acquired pneumonia ( CAP ) presenting with a similar hypoxemic respiratory failure and exploring the ensuing impact on outcome . Design . Prospect i ve , observational study . Setting . Multidisciplinary ICU , regional teaching hospital . Patients . Non- COPD patients with CPE or severe CAP . Measurements and results . Fifteen patients with CPE and eighteen with CAP were included . Both groups had similar low PaO2/FiO2 ratios at admission ; SAPS II , baseline pHa were lower in the CPE group than in the CAP group . Within the first NIPSV observation period ( 60 min ) , the oxygenation improved significantly in both CPE and CAP-groups ; respiratory rate ( RR ) significantly decreased in the CPE group ( P=0.005 ) , but it remained unchanged in the whole CAP group ; heart rate and mean arterial pressure significantly decreased in both groups . One patient ( 6.6 % ) in the CPE group and seven patients ( 38 % ) in the CAP group were intubated ( P=0.04 ) . The mean total time spent on NIPSV was 9.6±6.3 h in the CPE and 37.2±36 h in the CAP group ( P=0.01 ) . Unit mortality rate was 6.6 % in the CPE and 28 % in the CAP group ( P=0.2 ) . Upon inclusion , all but one CAP patients who were subsequently intubated had a bacteremic pneumonia ; unit mortality rate was 57 % in intubated- and 9 % in non-intubated CAP patients ( P=0.05 ) . Conclusions . NIPSV equally and rapidly improved oxygenation in non- COPD patients with CPE and severe CAP presenting with a similar hypoxemic respiratory failure , but the subsequent outcome was definitely different in the two groups , depending on the nature of the acute lung injury CONTEXT Nursing home residents with pneumonia are frequently hospitalized . Such transfers may be associated with multiple hazards of hospitalization as well as economic costs . OBJECTIVE To assess whether using a clinical pathway for on-site treatment of pneumonia and other lower respiratory tract infections in nursing homes could reduce hospital admissions , related complications , and costs . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized controlled trial of 680 residents aged 65 years or older in 22 nursing homes in Hamilton , Ontario , Canada . Nursing homes began enrollment between January 2 , 2001 , and April 18 , 2002 , with the last resident follow-up occurring July 4 , 2005 . Residents were eligible if they met a st and ardized definition of lower respiratory tract infection . INTERVENTIONS Treatment in nursing homes according to a clinical pathway , which included use of oral antimicrobials , portable chest radiographs , oxygen saturation monitoring , rehydration , and close monitoring by a research nurse , or usual care . MAIN OUTCOME MEASURES Hospital admissions , length of hospital stay , mortality , health-related quality of life , functional status , and cost . RESULTS Thirty-four ( 10 % ) of 327 residents in the clinical pathway group were hospitalized compared with 76 ( 22 % ) of 353 residents in the usual care group . Adjusting for clustering of residents in nursing homes , the weighted mean reduction in hospitalizations was 12 % ( 95 % confidence interval [ CI ] , 5%-18 % ; P = .001 ) . The mean number of hospital days per resident was 0.79 in the clinical pathway group vs 1.74 in the usual care group , with a weighted mean difference of 0.95 days per resident ( 95 % CI , 0.34 - 1.55 days ; P = .004 ) . The mortality rate was 8 % ( 24 deaths ) in the clinical pathway group vs 9 % ( 32 deaths ) in the usual care group , with a weighted mean difference of 2.9 % ( 95 % CI , -2.0 % to 7.9 % ; P = .23 ) . There were no significant differences between the groups in health-related quality of life or functional status . The clinical pathway result ed in an overall cost savings of US 1016 dollars per resident ( 95 % CI , 207 dollars-1824 dollars ) treated . CONCLUSION Treating residents of nursing homes with pneumonia and other lower respiratory tract infections with a clinical pathway can result in comparable clinical outcomes , while reducing hospitalizations and health care costs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00157612 In patients with acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) , a recent ARDS Network r and omized controlled trial demonstrated that a low tidal volume ( VT ) mechanical ventilation strategy ( 6 ml/kg ) reduced mortality by 22 % compared with traditional mechanical ventilation ( 12 ml/kg ) . In this study , we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network r and omized controlled trials . The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality . The risk of death ( before discharge home with unassisted breathing ) was highest in patients with sepsis ( 43 % ) ; intermediate in subjects with pneumonia ( 36 % ) , aspiration ( 37 % ) , and other risk factors ( 35 % ) ; and lowest in those with trauma ( 11 % ) ( p < 0.0001 ) . Despite these differences in mortality , there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor ( p = 0.76 , for interaction between ventilator group and risk factor ) . There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes : proportion of patients achieving unassisted breathing ( p = 0.59 ) , ventilator-free days ( p = 0.58 ) , or development of nonpulmonary organ failure ( p = 0.44 ) . Controlling for demographic and clinical covariates did not appreciably affect these results . After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions , there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups . In conclusion , we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS OBJECTIVES --To determine the prevalence , clinical correlates , and outcome of hypoxaemia in acutely ill children with respiratory symptoms . DESIGN -- Prospect i ve observational study . SETTING --Paediatric casualty ward of a referral hospital at 1670 m altitude in Nairobi , Kenya . SUBJECTS--256 Infants and children under 3 years of age with symptoms of respiratory infection . MAIN OUTCOME MEASURES --Prevalence of hypoxaemia , defined as arterial oxygen saturation < 90 % determined by pulse oximetry , and condition of patient on the fifth day after admission . RESULTS --Over half ( 151 ) of the children were hypoxaemic , and short term mortality was 4.3 times greater in these children . In contrast , the relative risk of a fatal outcome in children with radiographic pneumonia was only 1.03 times that of children without radiographic pneumonia . A logistic regression model showed that in 3 - 11 month old infants a respiratory rate > or = 70/min , grunting , and retractions were the best independent clinical signs for the prediction of hypoxaemia . In the older children a respiratory rate of > or = 60/min was the single best clinical predictor of hypoxaemia . The presence of hypoxaemia predicted radiographic pneumonia with a sensitivity of 71 % and specificity of 55 % . CONCLUSIONS --Over half the children presenting to this referral hospital with respiratory symptoms were hypoxaemic . A group of specific clinical signs seem useful in predicting hypoxaemia . The clear association of hypoxaemia with mortality suggests that the detection and effective treatment of hypoxaemia are important aspects of the clinical management of acute infections of the lower respiratory tract in children in hospital in developing regions OBJECTIVE Our objective was to evaluate the efficacy of noninvasive continuous positive airway pressure ( CPAP ) delivered by helmet in improving oxygenation in comparison with oxygen therapy in community-acquired pneumonia ( CAP ) . METHODS This was a multicenter , r and omized , controlled trial enrolling patients with CAP admitted to an ED with moderate hypoxemic acute respiratory failure ( ARF ) ( Pa(O(2))/Fi(O(2 ) ) ratio > or = 210 and < or = 285 ) . Patients were r and omized to helmet CPAP or st and ard oxygen therapy ( control group ) . The primary end point was the time to reach a Pa(O(2))/Fi(O(2 ) ) ratio > 315 . After reaching this value , patients r and omized to CPAP were switched to oxygen , and the proportion of subjects who could maintain a Pa(O(2))/Fi(O(2 ) ) ratio > 315 at 1 h was recorded . RESULTS Forty-seven patients were recruited : 20 r and omized to CPAP and 27 to controls . Patients r and omized to CPAP reached the end point in a median of 1.5 h , whereas controls reached the end point in 48 h ( P < .001 ) . The proportion of patients who reached the primary end point was 95 % ( 19/20 ) among the CPAP group and 30 % ( 8/27 ) among controls ( P < .001 ) . One hour after reaching the primary end point , 2/14 patients in the CPAP group maintained a Pa(O(2))/Fi(O(2 ) ) value > 315 . CONCLUSIONS CPAP delivered by helmet rapidly improves oxygenation in patients with CAP suffering from a moderate hypoxemic ARF . This trial represents a proof-of-concept evaluation of the potential usefulness of CPAP in patients with CAP The benefit of noninvasive pressure support ventilation ( NIPSV ) in avoiding the need for endotracheal intubation and reducing morbidity and mortality associated with endotracheal intubation was evaluated in 41 patients who presented with acute respiratory failure not related to chronic obstructive pulmonary disease ( COPD ) . Patients were r and omly assigned to receive conventional therapy ( n = 20 ) or conventional therapy plus NIPSV ( n = 21 ) . NIPSV was delivered to the patient by a face mask connected to a ventilator ( Puritan-Bennett 7200a ) set in inspiratory pressure support ( IPS ) mode . The mean levels of IPS , positive end-expiratory pressure ( PEEP ) , and fraction of inspired oxygen ( FIO2 ) were respectively 15 + /- 3 cm H2O , 4 + /- 2 cm H2O , and 57 + /- 22 % . The rate of endotracheal intubation ( 62 vs 70 % , p = 0.88 ) , the length of ICU stay ( 17 + /- 19 days vs 25 + /- 23 days , p = 0.16 ) , and the mortality rate ( 33 vs 50 % , p = 0.46 ) were not different between patients treated with NIPSV and those treated conventionally . Post hoc analysis suggested that in patients with PaCO2 > 45 mm Hg ( n = 17 ) , NIPSV was associated with a reduction in the rate of endotracheal intubation ( 36 vs 100 % , p = 0.02 ) , in the length of ICU stay ( 13 + /- 15 days vs 32 + /- 30 days , p = 0.04 ) , and in the mortality rate ( 9 vs 66 % , p = 0.06 ) . We conclude that NIPSV is of no benefit when used systematic ally in all forms of acute respiratory failure not related to COPD . A subgroup of patients , characterized by acute ventilatory failure and hypercapnia , may potentially benefit from this therapy and further studies are needed to focus on this aspect OBJECTIVE To evaluate the feasibility and the efficacy of early extubation and sequential noninvasive mechanical ventilation ( MV ) switched by pulmonary infection control window ( PIC window ) in chronic obstructive pulmonary disease ( COPD ) with exacerbated hypercapnic respiratory failure . METHODS Respiratory or Medical Intensive Care Units ( RICU/MICU ) of 12 teaching hospitals in China participated in this study . COPD patients with severe hypercapnic respiratory failure exacerbated by pulmonary infection , and for whom intubation and MV were indicated , were enrolled in the study . PIC window was defined as the time point when pulmonary infection was considered under control based on clinical parameters . At PIC window , all the cases were r and omly assigned to sequential MV group or conventional MV group . The invasive MV duration , ventilator-associated pneumonia ( VAP ) , days in ICU and mortality rate in both groups were measured . RESULTS Ninety cases were enrolled . Compared with conventional MV group ( n = 43 ) sequential MV group ( n = 47 ) had shorter duration of invasive MV [ ( 6.4 + /- 4.4 ) , ( 11.3 + /- 6.2 ) d , P = 0.000 ] , lower rate of VAP ( 3/47 , 12/43 , P = 0.014 ) , fewer days in ICU [ ( 12 + /- 8) , ( 16 + /- 11 ) d , P = 0.047 ] and lower mortality rate ( 1/47 , 7/43 , P = 0.025 ) . CONCLUSION Early extubation followed by non-invasive MV initiated at the point of PIC window may decrease the duration of invasive MV and improve the prognosis BACKGROUND Avoiding intubation is a major goal in the management of respiratory failure , particularly in immunosuppressed patients . Nevertheless , there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients . METHODS We conducted a prospect i ve , r and omized trial of intermittent noninvasive ventilation , as compared with st and ard treatment with supplemental oxygen and no ventilatory support , in 52 immunosuppressed patients with pulmonary infiltrates , fever , and an early stage of hypoxemic acute respiratory failure . Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen . The ventilation periods lasted at least 45 minutes . Decisions to intubate were made according to st and ard , predetermined criteria . RESULTS The base-line characteristics of the two groups were similar ; each group of 26 patients included 15 patients with hematologic cancer and neutropenia . Fewer patients in the noninvasive-ventilation group than in the st and ard-treatment group required endotracheal intubation ( 12 vs. 20 , P=0.03 ) , had serious complications ( 13 vs. 21 , P=0.02 ) , died in the intensive care unit ( 10 vs. 18 , P=0.03 ) , or died in the hospital ( 13 vs. 21 , P=0.02 ) . CONCLUSIONS In selected immunosuppressed patients with pneumonitis and acute respiratory failure , early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge Objectives : To compare the efficacy of noninvasive pressure support ventilation ( NIPSV ) in acute decompensation in chronic obstructive pulmonary disease ( COPD ) by means of a bi-level positive airway pressure support system ( BiPAP ) in a sequential mode with medical therapy alone ; to assess the short-term physiologic effects of the device on gas exchange ; and to compare patients successfully ventilated with NIPSV with those in whom NIPSV failed . Design : A prospect i ve case series with historically matched control study . Setting : A general intensive care unit ( ICU ) of a university hospital . Patients : We evaluated the efficacy of administration of NIPSV in 42 COPD patients and compared this with st and ard treatment in 42 matched historical control COPD patients . Interventions : NIPSV was performed in a sequential mode , i. e. , BiPAP in the spontaneous mode was used for at least 30 min every 3 h. Between periods of ventilation , patients could be systematic ally returned to BiPAP when the arterial oxygen saturation was < 0.85 or when the respiratory rate was > 30 breaths/min . Measurements and results : Success rate , mortality , duration of ventilatory assistance , and length of ICU stay were recorded . Eleven of the 42 patients ( 26 % ) in the NIPSV group needed tracheal intubation compared with 30 of the 42 control patients ( 71 % ) . The 31 patients in whom NIPSV was successful were ventilated for a mean of 6 ± 3 days . In-hospital mortality was not significantly different in the treated versus the control group , but the duration of ventilatory assistance ( 7 ± 4 days vs 15 ± 10 days , p < 0.01 ) and the length of ICU stay ( 9 ± 4 days vs 21 ± 12 , p < 0.01 ) were both shortened by NIPSV . BiPAP was effective in correcting gas exchange abnormalities . The pH values , measured after 45 min of BiPAP with optimal setting s , in the success ( 7.38 ± 0.04 ) and failure ( 7.28 ± 0.04 ) patients were significantly different ( p < 0.05 ) . Conclusions : NIPSV , performed with a sequential mode , may be used in the management of patients with acute exacerbations of COPD BACKGROUND We hypothesized that the total face mask ( TFM ) would be perceived as more comfortable than a st and ard oronasal mask ( ONM ) by patients receiving noninvasive mechanical ventilation ( NIV ) therapy for acute respiratory failure ( ARF ) and would be quicker to apply by respiratory therapists . METHODS Sixty patients presenting with ARF were r and omized to receive NIV via either an ONM or a TFM . Mask comfort and dyspnea were assessed using visual analog scores . Other outcomes included time required to apply , vital signs and gas exchange at set time points , and early NIV discontinuation rates ( ie , stoppage while still requiring ventilatory assistance ) . RESULTS Mask comfort and dyspnea scores were similar for both groups through 3 h of use . The time required to apply the mask ( 5 min [ interquartile range ( IQR ) , 2 - 8 ] vs 3.5 min [ IQR , 1.9 - 5 ] ) , and duration of use ( 15.7 h [ IQR , 4.0 - 49.8 ] ) vs 6.05 h [ IQR , 0.9 - 56.7 ] ) were not significantly different between the ONM and the TFM group , respectively . Except for heart rate , which was higher at baseline in the TFM group , no differences in vital signs or gas exchange were detected between the groups during the first 3 h ( P > .05 ) . Early NIV discontinuation rates were similar for both the ONM group and TFM group ( 40 % vs 57.1 % ) ; however , eight patients in the TFM group were switched to an ONM within 3 h , and none from the ONM group was switched to a TFM ( P < .05 ) . CONCLUSIONS Among patients with ARF requiring NIV , the ONM and TFM were perceived to be equally comfortable and had similar application times . Early NIV discontinuation rates , improvements in vital signs and gas exchange , and intubation and mortality rates were also similar . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00686257 ; URL : www . clinical trials.gov Objective : To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease . Design : Multicenter , prospect i ve , r and omized , controlled trial . Setting : Seven intensive care units . Patients : A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea , Paco2 > 45 mm Hg and two among the following factors : pH < 7.35 , Paco2 < 50 mm Hg , respiratory rate > 25/min . Interventions : Noninvasive ventilation r and omly applied with or without helium ( inspired oxygen fraction 0.35 ) via a face mask . Measurements and Main Results : Duration and complications of NIV and mechanical ventilation , endotracheal intubation , discharge from intensive care unit and hospital , mortality at day 28 , adverse and serious adverse events were recorded . Follow-up lasted until 28 days since enrollment . Intubation rate did not significantly differ between groups ( 24.5 % vs. 30.4 % with or without helium , p = .35 ) . No difference was observed in terms of improvement of arterial blood gases , dyspnea , and respiratory rate between groups . Duration of noninvasive ventilation , length of stay , 28-day mortality , complications and adverse events were similar , although serious adverse events tended to be lower with helium ( 10.8 % vs. 19.6 % , p = .08 ) . Conclusions : Despite small trends favoring helium , this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease |
11,149 | 31,798,468 | Engagement and adherence rates were low .
Qualitative analysis revealed that users liked interventions with a game-like feel and relatable , interactive content .
Educational material s were perceived as boring , and users were put off by non-appealing interfaces and technical glitches .
Conclusions : Digital interventions work better than no intervention to improve depression in young people when results of different studies are pooled together .
However , these interventions may only be of clinical significance when use is highly supervised .
Digital interventions do not work better than active alternatives regardless of the level of support . | Background : A major challenge in providing mental health interventions for young people is making such interventions accessible and appealing to those most in need .
Online and app-based forms of therapy for mental health are burgeoning .
It is therefore crucial to identify features that are most effective and engaging for young users .
Objectives : This study reports a systematic review and meta- analysis of digital mental health interventions and their effectiveness in addressing anxiety and depression in young people to determine factors that relate to outcomes , adherence , and engagement with such interventions . | Background Prevention of the onset of depression in adolescence may prevent social dysfunction , teenage pregnancy , substance abuse , suicide , and mental health conditions in adulthood . New technologies allow delivery of prevention programs scalable to large and disparate population s. Objective To develop and test the novel mobile phone delivery of a depression prevention intervention for adolescents . We describe the development of the intervention and the results of participants ’ self-reported satisfaction with the intervention . Methods The intervention was developed from 15 key messages derived from cognitive behavioral therapy ( CBT ) . The program was fully automated and delivered in 2 mobile phone messages/day for 9 weeks , with a mixture of text , video , and cartoon messages and a mobile website . Delivery modalities were guided by social cognitive theory and marketing principles . The intervention was compared with an attention control program of the same number and types of messages on different topics . A double-blind r and omized controlled trial was undertaken in high schools in Auckl and , New Zeal and , from June 2009 to April 2011 . Results A total of 1348 students ( 13–17 years of age ) volunteered to participate at group sessions in schools , and 855 were eventually r and omly assigned to groups . Of these , 835 ( 97.7 % ) self-completed follow-up question naires at postprogram interviews on satisfaction , perceived usefulness , and adherence to the intervention . Over three-quarters of participants viewed at least half of the messages and 90.7 % ( 379/418 ) in the intervention group reported they would refer the program to a friend . Intervention group participants said the intervention helped them to be more positive ( 279/418 , 66.7 % ) and to get rid of negative thoughts ( 210/418 , 50.2%)—significantly higher than proportions in the control group . Conclusions Key messages from CBT can be delivered by mobile phone , and young people report that these are helpful . Change in clinician-rated depression symptom scores from baseline to 12 months , yet to be completed , will provide evidence on the effectiveness of the intervention . If proven effective , this form of delivery may be useful in many countries lacking widespread mental health services but with extensive mobile phone coverage . Clinical Trial Australia New Zeal and Clinical Trials Registry ( ACTRN ) : 12609000405213 ; http://www.anzctr.org.au/trial_view.aspx?ID=83667 ( Archived by WebCite at http://www.webcitation.org/64aueRqOb Background The use of mobile apps for health and well being promotion has grown exponentially in recent years . Yet , there is currently no app- quality assessment tool beyond “ star”-ratings . Objective The objective of this study was to develop a reliable , multidimensional measure for trialling , classifying , and rating the quality of mobile health apps . Methods A literature search was conducted to identify articles containing explicit Web or app quality rating criteria published between January 2000 and January 2013 . Existing criteria for the assessment of app quality were categorized by an expert panel to develop the new Mobile App Rating Scale ( MARS ) subscales , items , descriptors , and anchors . There were sixty well being apps that were r and omly selected using an iTunes search for MARS rating . There were ten that were used to pilot the rating procedure , and the remaining 50 provided data on interrater reliability . Results There were 372 explicit criteria for assessing Web or app quality that were extracted from 25 published papers , conference proceedings , and Internet re sources . There were five broad categories of criteria that were identified including four objective quality scales : engagement , functionality , aesthetics , and information quality ; and one subjective quality scale ; which were refined into the 23-item MARS . The MARS demonstrated excellent internal consistency ( alpha = .90 ) and interrater reliability intraclass correlation coefficient ( ICC = .79 ) . Conclusions The MARS is a simple , objective , and reliable tool for classifying and assessing the quality of mobile health apps . It can also be used to provide a checklist for the design and development of new high quality health apps AIM Preventive intervention and treatment using internet-based cognitive behaviour therapy ( iCBT ) can be easily administered to school students , as they are quite familiar with internet tools . This study aims to investigate the effectiveness and contribution of iCBT to mental healthcare in a school setting . METHODS Eighty Japanese high school boys who were participating in a sports specialist course were enrolled in this study . The participants were r and omly assigned to either the iCBT intervention group or the control group . Both programmes were administered for 4 weeks . To evaluate the effects , physical and mental health problems and self-efficacy were assessed . RESULTS The mean number of times that the iCBT website was accessed during the intervention period was 16.9 , and the mean access frequency ( percentage of the number of times the website was accessed during the intervention period ) was 40.1 % in the iCBT group . A statistically significant interaction between group and time in favour of the iCBT group was observed based on the Kessler-6 ( K6 ) scale for depression and anxiety . CONCLUSIONS The results suggest that a school mental healthcare programme using iCBT is suitable for students and useful for coping with stress and reducing depressed mood and anxiety in young people , especially athletes , who are regarded as needing special mental health support Background Depression is a serious mental health problem , whose first onset is usually in adolescence . Online treatment may offer a solution for the current undertreatment of depression in youth . For adults with depressive symptoms , the effectiveness of Internet-based cognitive behavioral therapy has been demonstrated . This study is one of the first r and omized controlled trials to investigate the effectiveness online depression treatment for young people with depressive complaints and the first to focus on an online group course . Objective To evaluate and discuss the effectiveness of a guided Web-based group course called Grip op Je Dip ( Master Your Mood [ MYM ] ) , design ed for young people aged 16 to 25 years with depressive symptoms , in comparison with a wait-listed control group . Methods We r and omly assigned 244 young people with depressive symptoms to the online MYM course or to a waiting-list control condition . The primary outcome measure was treatment outcome after 3 months on the Center for Epidemiologic Studies Depression Scale . Secondary outcomes were anxiety ( measured by the Hospital Anxiety and Depression Scale ) and mastery ( Mastery Scale ) . We studied the maintenance of effects in the MYM group 6 months after baseline . Missing data were imputed . Results The MYM group ( n = 121 ) showed significantly greater improvement in depressive symptoms at 3 months than the control group ( n = 123 ) ( t 187 = 6.62 , P < .001 ) , with a large between-group effect size of d = 0.94 ( 95 % confidence interval [ CI ] 0.64–1.23 ) . The MYM group also showed greater improvement in anxiety ( t 187 = 3.80 , P < .001 , d = 0.49 , 95 % CI 0.24–0.75 ) and mastery ( t 187 = 3.36 , P = .001 , d = 0.44 , 95 % CI 0.19–0.70 ) . At 12 weeks , 56 % ( 68/121 ) of the participants in the MYM group and 20 % ( 24/123 ) in the control group showed reliable and clinical ly significant change . This between-group difference was significant ( χ2 1 = 35.0 , P < .001 ) and yielded a number needed to treat of 2.7 . Improvements in the MYM group were maintained at 6 months . A limitation is the infeasibility of comparing the 6-month outcomes of the MYM and control groups , as the controls had access to MYM after 3 months . Conclusions The online group course MYM was effective in reducing depressive symptoms and anxiety and in increasing mastery in young people . These effects persisted in the MYM group at 6 months . Trial Registration Nederl and s Trial Register : NTR1694 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1694 ( Archived by WebCite at http://www.webcitation.org/683SBoeGV Background Up to 9 % of young people suffer from depression . Unfortunately , many in need of help remain untreated . The Internet offers anonymous ways to help depressed youth , especially those who are reluctant to search for help because of fear of stigma . Objective Our goal was to evaluate the effectiveness of an individual chat treatment based on Solution-Focused Brief Therapy ( SFBT ) to young individuals aged 12 - 22 years with depressive symptoms by comparing it to a waiting list control group . Methods For this study , 263 young people with depressive symptoms were r and omized to the Web-based SFBT intervention , PratenOnline , or to a waiting list control condition . The chat treatment was delivered by trained professionals . Groups were compared on depressive complaints as measured by the Center for Epidemiologic Studies Depression Scale ( CES-D ) after 9 weeks and 4.5 months . For the chat group only , changes in depressive symptoms at 7.5 months after baseline were explored . Results The experimental SFBT condition ( n=131 ) showed significantly greater improvement than the waiting list condition ( n=132 ) in depressive symptoms at 9 weeks and 4.5 months on the CES-D , with a small between group effect size at 9 weeks ( d=0.18 , 95 % CI -0.10 to 0.47 ) and a large effect size at 4.5 months ( d=0.79 , 95 % CI 0.45 - 1.08 ) . The percentage of participants showing a reliable and clinical ly significant change in depression was significantly larger for the SFBT intervention at 4.5 months only ( 28.2 % vs 11.4 % for the waiting list , P<.001 , number needed to treat=6 ) . At 7.5 months , the SFBT group showed further improvements . However , results have to be considered carefully because of high attrition rates . Conclusions The Web-based SFBT chat intervention of PratenOnline was more effective than a waiting list control group in reducing depressive symptoms , and effects were larger at follow-up then at post-treatment . More studies are needed to find out if outcomes will be replicated , especially for those younger than 18 year old . Trial Registration Netherl and s Trial Register : NTR 1696 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=1696 ( Archived by WebCite at http://www.webcitation.org/6DspeYWrJ ) Background Internet-based cognitive behavioural therapy ( ICBT ) is a promising approach to the prevention and reduction of depressive symptoms among adolescents . This study aim ed to evaluate the feasibility and efficacy of disseminating a self-directed internet-based mental health intervention ( MoodGYM ) in senior high schools . It also sought to investigate possible effects of tailored and weekly e-mail reminders on initial uptake and adherence to the intervention . Method A baseline survey was conducted in four senior high schools in two Norwegian municipalities ( n = 1337 ) . 52.8 % ( 707/1337 ) of the students consented to further participation in the trial and were r and omly allocated to one of three MoodGYM intervention groups ( tailored weekly e-mail reminder ( n = 175 ) , st and ardized weekly e-mail reminder ( n = 176 ) or no e-mail reminder ( n = 175 ) ) or a waitlist control group ( n = 180 ) . We tested for effects of the intervention on depression and self-esteem using multivariate analysis of variance , effects of tailored e-mail and self-reported current need of help on initial uptake of the intervention using logistic regression and the effect of weekly e-mails on adherence using ordinal regression . Results There was substantial non-participation from the intervention , with only 8.5 % ( 45/527 ) participants logging on to MoodGYM , and few proceeding beyond the first part of the programme . No significant effect on depression or self-esteem was found among the sample as a whole or among participants with elevated depression scores at baseline . Having a higher average grade in senior high school predicted initial uptake of the intervention , but tailored e-mail and self-reported current need of help did not . Weekly e-mail prompts did not predict adherence . The main reasons for non-use reported were lack of time/forgetting about it and doubt about the usefulness of the program . Conclusion Overall , disseminating a self-directed internet-based intervention to a school population proved difficult despite steps taken to reduce barriers in terms of tailoring feedback and dispatching weekly e-mail reminders . Providing mental health interventions within the school environment is likely to ensure better uptake among senior high school students , but there is a need to effectively communicate that such programmes can be helpful . Trial registration The trial was registered retrospectively as Background GPs detect at best 50c of mental health problems in young people . Barriers to detecting mental health problems include lack of screening tools , limited appointment times and young people ’s reluctance to report mental health symptoms to GPs . The mobiletype program is a mobile phone mental health assessment and management application which monitors mood , stress and everyday activities then transmits this information to general practitioners ( GPs ) via a secure website in summary format for medical review . The current aims were to examine : ( i ) mobiletype as a clinical assistance tool , ii ) doctor-patient rapport and , iii ) pathways to care . Methods We conducted a r and omised controlled trial in primary care with patients aged 14 to 24 years recruited from rural and metropolitan general practice s. GPs identified and referred eligible participants ( those with mild or more mental health concerns ) who were r and omly assigned to either the intervention group ( where mood , stress and daily activities were monitored ) or the attention-comparison group ( where only daily activities were monitored ) . Both groups self-monitored for 2 to 4 weeks and review ed the monitoring data with their GP . GPs , participants and research ers were blind to group allocation at r and omisation . GPs assessed the mobiletype program as a clinical assistant tool . Doctor-patient rapport was assessed using the General Practice Assessment Question naire Communication and Enablement subscales , and the Trust in Physician Scale ( TPS ) . Pathways to care was measured using The Party Project ’s Exit Interview . Results Of the 163 participants assessed for eligibility , 118 were r and omised and 114 participants were included in analyses ( intervention n = 68 , attention-comparison n = 46 ) . T-tests showed that the intervention program increased underst and ing of patient mental health , assisted in decisions about medication/referral and helped in diagnosis when compared to the attention-comparison program . Mixed model analysis showed no differences in GP-patient rapport nor in pathways to care . Conclusions We conducted the first RCT of a mobile phone application in the mental health assessment and management of youth mental health in primary care . This study suggests that mobiletype has much to offer GPs in the often difficult and time-consuming task of assessment and management of youth mental health problems in primary care . Trial registration Clinical Trials.gov 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 BACKGROUND Research has consistently identified a disparity between the prevalence of mental health concerns among young adults and their rates of formal help seeking . However , a few r and omised controlled trials have identified effective interventions for increasing formal help seeking among young adults . The aim of this study was to evaluate the effectiveness of a brief online psychoeducational intervention , targeting depression , anxiety and suicide stigma , for increasing positive attitudes towards help seeking and increasing help seeking intentions among young adults . METHOD The study followed a single-blind parallel group r and omized controlled trial design with 67 young adult ( 18 - 25 years ) Australian participants , assigned to receive online psychoeducation ( n=33 ) or online attention-matched control information ( n=34 ) over 3 weeks . Participants in the experimental group received information on depression , anxiety , and suicide . The control group received information unrelated to mental health . Primary outcome measures were mental health literacy , mental illness stigma , attitudes toward professional help seeking and intentions to seek help . Secondary outcome variables were symptomology , satisfaction and adherence . RESULTS Significant between-group differences were found for the pre- to post-test , including increased anxiety literacy ( Cohen׳s d=0.65 ) , decreased depression stigma ( d=0.53 ) , and increased help seeking attitudes and intentions for the experimental group ( d=0.58 and d=0.53 , respectively ) . LIMITATIONS Due to the small sample size and homogenous nature of the sample , generalisations should be made with caution . CONCLUSIONS This study demonstrates the utility and effectiveness of a brief online psychoeducation intervention for promoting help seeking among young adults BACKGROUND Depression often starts in adolescence making it an ideal time to intervene . We developed a universal cognitive behavioural therapy-based programme ( MEMO CBT ) to be delivered via multimedia mobile phone messages for teens . METHODS We conducted a prospect i ve multicentre , r and omised , placebo-controlled superiority trial in 15 high schools in Auckl and , New Zeal and , comparing MEMO CBT with a control programme [ MEMO control ] matched for intensity and type of message but with alternative content not targeting depression . The primary outcome was the change in score on the Children 's Depression Rating Scale-Revised from baseline to 12 months . Secondary outcomes included the change in scores in the self-reported Reynold 's Adolescent Depression Rating Scale-Second Edition , the Moods and Feelings Question naire , suicidal ideation using selected items from the Youth Risk Behaviour Survey , the Pediatric Quality of Life question naire , 12-month period prevalence of the diagnosis of depressive disorder using the Kiddie-Schedule for Affective Disorders and Schizophrenia , and students ' ratings of their satisfaction with the programme . RESULTS Eight hundred and fifty-five students ( 13 - 17 years old , mean 14.3 years ) were r and omly assigned to MEMO CBT ( 426 ) or to MEMO Control ( 429 ) . Participants ( 68 % female ) had a mean CDRS-R at baseline of 21.5 ( SD : 5 ) . Overall 394 ( 93 % ) from the intervention group and 392 ( 91 % ) from the control group were followed up at 12 months . At the end of the intervention ( approximately 9 weeks ) the mean CDRS-R scores were 20.8 in the intervention group versus 20.4 in the control group , and at 12 months they were 22.4 versus 22.4 ( p value for difference in change from baseline = 0.3 ) . There was no obvious association between the amount of the intervention viewed by participants and outcomes . CONCLUSIONS There was no evidence of benefit from the mobile phone CBT intervention compared with a control programme . Universal depression prevention remains a challenge Background Youth mental health is a significant public health concern due to the high prevalence of mental health problems in this population and the low rate of those affected seeking help . While it is increasingly recognized that prevention is better than cure , most youth prevention programs have utilized interventions based on clinical treatments ( eg , cognitive behavioral therapy ) with inconsistent results . Objective This study explores the feasibility of the online delivery of a youth positive psychology program , Bite Back , to improve the well-being and mental health outcomes of Australian youth . Further aims were to examine rates of adherence and attrition , and to investigate the program ’s acceptability . Methods Participants ( N=235 ) aged 12 - 18 years were r and omly assigned to either of two conditions : Bite Back ( n=120 ) or control websites ( n=115 ) . The Bite Back website comprised interactive exercises and information across a variety of positive psychology domains ; the control condition was assigned to neutral entertainment-based websites that contained no psychology information . Participants in both groups were instructed to use their allocated website for 6 consecutive weeks . Participants were assessed pre- and postintervention on the Depression Anxiety Stress Scale-Short form ( DASS-21 ) and the Short Warwick-Edinburgh Mental Well-Being Scale ( SWEMWBS ) . Results Of the 235 r and omized participants , 154 ( 65.5 % ) completed baseline and post measures after 6 weeks . Completers and dropouts were equivalent in demographics , the SWEMWBS , and the depression and anxiety subscales of the DASS-21 , but dropouts reported significantly higher levels of stress than completers . There were no differences between the Bite Back and control conditions at baseline on demographic variables , DASS-21 , or SWEMWBS scores . Qualitative data indicated that 49 of 61 Bite Back users ( 79 % ) reported positive experiences using the website and 55 ( 89 % ) agreed they would continue to use it after study completion . Compared to the control condition , participants in the Bite Back condition with high levels of adherence ( usage of the website for 30 minutes or more per week ) reported significant decreases in depression and stress and improvements in well-being . Bite Back users who visited the site more frequently ( ≥3 times per week ) reported significant decreases in depression and anxiety and improvements in well-being . No significant improvements were found among Bite Back users who demonstrated low levels of adherence or who used the website less frequently . Conclusions Results suggest that using an online positive psychology program can decrease symptoms of psychopathology and increase well-being in young people , especially for those who use the website for 30 minutes or longer per week or more frequently ( ≥3 times per week ) . Acceptability of the Bite Back website was high . These findings are encouraging and suggest that the online delivery of positive psychology programs may be an alternate way to address mental health issues and improve youth well-being nationally . 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 ) Background The recent growth of positive psychology has led to a proliferation in exercises to increase positive thoughts , behaviors , and emotions . Preliminary evidence suggests that these exercises hold promise as an approach for reducing depressive symptoms . These exercises are typically research ed in isolation as single exercises . The current study examined the acceptability of several multi-exercise packages using online dissemination . Objective The purpose of this study was to investigate methods of dissemination that could increase the acceptability and effectiveness of positive psychology exercises . To achieve this goal , we compared the use of positive psychology exercises when delivered in packages of 2 , 4 , or 6 exercises . Methods Self-help – seeking participants enrolled in this study by visiting an online research portal . Consenting participants were r and omly assigned to receive 2 , 4 , or 6 positive psychology exercises ( or assessment s only ) over a 6-week period . These exercises drew from the content of group positive psychotherapy . Participants visited an automated website that distributed exercise instructions , provided email reminders , and contained the baseline and follow-up assessment s. Following each exercise , participants rated their enjoyment of the exercise , answered how often they had used each technique , and completed outcome measures . Results In total , 1364 individuals consented to participate . Attrition rates across the 2- , 4- , and 6-exercise conditions were similar at 55.5 % ( 181/326 ) , 55.8 % ( 203/364 ) , and 52.7 % ( 168/319 ) respectively but were significantly greater than the attrition rate of 42.5 % ( 151/355 ) for the control condition ( χ2 3 = 16.40 , P < .001 ) . Participants in the 6-exercise condition were significant more likely than participants in the 4-exercise condition to use both the third ( F 1,312 = 5.61 , P = .02 ) and fourth ( F 1,313 = 6.03 , P = .02 ) exercises . For 5 of the 6 exercises , enjoyment was related to continued use of the exercise at 6-week follow-up ( r ’s = .12 to .39 ) . All conditions produced significant reductions in depressive symptoms ( F 1,656 = 94.71 , P < .001 ) ; however , a significant condition by time interaction ( F 3,656 = 4.77 , P = .003 ) indicated that this reduction was larger in the groups that received 2 or 4 exercises compared with the 6-exercise or control condition . Conclusion Increasing the number of exercises presented to participants increased the use of the techniques and did not increase dropout . Participants may be more likely to use these skills when presented with a variety of options . Increasing the number of exercises delivered to participants produced a curvilinear relationship with those in the 2- and 4-exercise conditions reporting larger decreases in depressive symptoms than participants in the 6-exercise or control conditions . Although research generally offers a single exercise to test isolate effects , this study supports that study ing variability in dissemination can produce important findings 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 ) Background Depression in adolescents and young adults is a major mental health condition that requires attention . Research suggests that approaches that include spiritual concepts and are delivered through an online platform are a potentially beneficial approach to treating/managing depression in this population . The purpose of this study was to evaluate the effectiveness of an 8-week online spirituality informed e-mental health intervention ( the LEAP Project ) on depression severity , and secondary outcomes of spiritual well-being and self-concept , in adolescents and young adults with major depressive disorder of mild to moderate severity . Methods A parallel group , r and omized , waitlist controlled , assessor-blinded clinical pilot trial was conducted in Calgary , Alberta , Canada . The sample of 62 participants with major depressive disorder ( DSM-IV-TR ) was defined by two age subgroups : adolescents ( ages 13 to 18 years ; n = 31 ) and young adults ( ages 19 to 24 years ; n = 31 ) . Participants in each age subgroup were r and omized into the study arm ( intervention initiated upon enrolment ) or the waitlist control arm ( intervention initiated after an 8-week wait period ) . Comparisons were made between the study and waitlist control arms at week 8 ( the point where study arm had completed the intervention and the waitlist control arm had not ) and within each arm at four time points over 24-week follow-up period . Results At baseline , there was no statistical difference between study and waitlist participants for both age subgroups for all three outcomes of interest . After the intervention , depression severity was significantly reduced ; comparison across arms at week 8 and over time within each arm and both age subgroups . Spiritual well-being changes were not significant , with the exception of an improvement over time for the younger participants in the study arm ( p = 0.01 at week 16 and p = 0.0305 at week 24 ) . Self-concept improved significantly for younger participants immediately after the intervention ( p = 0.045 comparison across arms at week 8 ; p = 0.0175 in the waitlist control arm ) and over time in the study arm ( p = 0.0025 at week 16 ) . In the older participants , change was minimal , with the exception of a significant improvement in one of six factors ( vulnerability ) in study arm over time ( p = 0.025 at week 24 ) . Conclusions The results of the LEAP Project pilot trial suggest that it is an effective , online intervention for youth ages 13 to 24 with mild to moderate major depressive disorder with various life situations and in a limited way on spiritual well-being and self-concept . Trial registration Clinical Trials.gov NCT00985686 . Registered 24 September 2009 Objective To evaluate whether a new computerised cognitive behavioural therapy intervention ( SPARX , Smart , Positive , Active , Realistic , X-factor thoughts ) could reduce depressive symptoms in help seeking adolescents as much or more than treatment as usual . Design Multicentre r and omised controlled non-inferiority trial . Setting 24 primary healthcare sites in New Zeal and ( youth clinics , general practice s , and school based counselling services ) . Participants 187 adolescents aged 12 - 19 , seeking help for depressive symptoms , with no major risk of self harm and deemed in need of treatment by their primary healthcare clinicians : 94 were allocated to SPARX and 93 to treatment as usual . Interventions Computerised cognitive behavioural therapy ( SPARX ) comprising seven modules delivered over a period of between four and seven weeks , versus treatment as usual comprising primarily face to face counselling delivered by trained counsellors and clinical psychologists . Outcomes The primary outcome was the change in score on the children ’s depression rating scale-revised . Secondary outcomes included response and remission on the children ’s depression rating scale-revised , change scores on the Reynolds adolescent depression scale-second edition , the mood and feelings question naire , the Kazdin hopelessness scale for children , the Spence children ’s anxiety scale , the paediatric quality of life enjoyment and satisfaction question naire , and overall satisfaction with treatment ratings . Results 94 participants were allocated to SPARX ( mean age 15.6 years , 62.8 % female ) and 93 to treatment as usual ( mean age 15.6 years , 68.8 % female ) . 170 adolescents ( 91 % , SPARX n=85 , treatment as usual n=85 ) were assessed after intervention and 168 ( 90 % , SPARX n=83 , treatment as usual n=85 ) were assessed at the three month follow-up point . Per protocol analyses ( n=143 ) showed that SPARX was not inferior to treatment as usual . Post-intervention , there was a mean reduction of 10.32 in SPARX and 7.59 in treatment as usual in raw scores on the children ’s depression rating scale-revised ( between group difference 2.73 , 95 % confidence interval −0.31 to 5.77 ; P=0.079 ) . Remission rates were significantly higher in the SPARX arm ( n=31 , 43.7 % ) than in the treatment as usual arm ( n=19 , 26.4 % ) ( difference 17.3 % , 95 % confidence interval 1.6 % to 31.8 % ; P=0.030 ) and response rates did not differ significantly between the SPARX arm ( 66.2 % , n=47 ) and treatment as usual arm ( 58.3 % , n=42 ) ( difference 7.9 % , −7.9 % to 24 % ; P=0.332 ) . All secondary measures supported non-inferiority . Intention to treat analyses confirmed these findings . Improvements were maintained at follow-up . The frequency of adverse events classified as “ possibly ” or “ probably ” related to the intervention did not differ between groups ( SPARX n=11 ; treatment as usual n=11 ) . Conclusions SPARX is a potential alternative to usual care for adolescents presenting with depressive symptoms in primary care setting s and could be used to address some of the unmet dem and for treatment . Trial registration Australian New Zeal and Clinical Trials ACTRN12609000249257 Abstract Objective : This study examined the feasibility of a prototype Web-based acceptance and commitment therapy ( ACT ) program for preventing mental health problems among college students . Participants : Undergraduate first-year students ( N = 76 ) participated between May and November 2011 . Methods : Participants were r and omized to ACT or a waitlist , with assessment s conducted at baseline , posttherapy , and 3-week follow-up . Waitlist participants accessed the program after the second assessment . Results : Program usability/usage data indicated high program acceptability . Significant improvements were found for ACT knowledge , education values , and depression with ACT relative to waitlist . Subgroup analyses indicated that ACT decreased depression and anxiety relative to waitlist among students with at least minimal distress . Within the ACT condition , significant improvements were observed from baseline to 3-week follow-up on all outcome and process measures . Conclusions : Results provide preliminary support for the feasibility of a Web-based ACT prevention program OBJECTIVE To examine the results of a r and omized clinical trial ( RCT ) of Teen Online Problem Solving ( TOPS ) , an online problem solving therapy model , in increasing problem-solving skills and decreasing depressive symptoms and global distress for caregivers of adolescents with traumatic brain injury ( TBI ) . METHOD Families of adolescents aged 11 - 18 who sustained a moderate to severe TBI between 3 and 19 months earlier were recruited from hospital trauma registries . Participants were assigned to receive a web-based , problem-solving intervention ( TOPS , n = 20 ) , or access to online re sources pertaining to TBI ( Internet Re source Comparison ; IRC ; n = 21 ) . Parent report of problem solving skills , depressive symptoms , global distress , utilization , and satisfaction were assessed pre- and posttreatment . Groups were compared on follow-up scores after controlling for pretreatment levels . Family income was examined as a potential moderator of treatment efficacy . Improvement in problem solving was examined as a mediator of reductions in depression and distress . RESULTS Forty-one participants provided consent and completed baseline assessment s , with follow-up assessment s completed on 35 participants ( 16 TOPS and 19 IRC ) . Parents in both groups reported a high level of satisfaction with both interventions . Improvements in problem solving skills and depression were moderated by family income , with caregivers of lower income in TOPS reporting greater improvements . Increases in problem solving partially mediated reductions in global distress . CONCLUSIONS Findings suggest that TOPS may be effective in improving problem solving skills and reducing depressive symptoms for certain subsets of caregivers in families of adolescents with TBI OBJECTIVE The study examined the relative efficacy of online ( NET ) versus clinic ( CLIN ) delivery of cognitive behavior therapy ( CBT ) in the treatment of anxiety disorders in adolescents . METHOD Participants included 115 clinical ly anxious adolescents aged 12 to 18 years and their parent(s ) . Adolescents were r and omly assigned to NET , CLIN , or wait list control ( WLC ) conditions . The treatment groups received equivalent CBT content . Clinical diagnostic interviews and question naire assessment s were completed 12 weeks after baseline and at 6- and 12-month follow-ups . RESULTS Assessment at 12 weeks post-baseline showed significantly greater reductions in anxiety diagnoses and anxiety symptoms for both NET and CLIN conditions compared with the WLC . These improvements were maintained or further enhanced for both conditions , with minimal differences between them , at 6- and 12-month follow-ups . Seventy-eight percent of adolescents in the NET group ( completer sample ) no longer met criteria for the principal anxiety diagnosis at 12-month follow-up compared with 80.6 % in the CLIN group . Ratings of treatment credibility from both parents and adolescents were high for NET and equivalent to CLIN . Satisfaction ratings by adolescents were equivalent for NET and CLIN conditions , whereas parents indicated slightly higher satisfaction ratings for the CLIN format . CONCLUSIONS Online delivery of CBT , with minimal therapist support , is equally efficacious as clinic-based , face-to-face therapy in the treatment of anxiety disorders among adolescents . This approach offers a credible alternative to clinic-based therapy , with benefits of reduced therapist time and greater accessibility for families who have difficulty accessing clinic-based CBT OBJECTIVE To explore patterns of internet use by young people in Australia and assess the usefulness of online re sources for mental health problems , exploring functionality that may be relevant in the development of online mental health services . DESIGN AND PARTICIPANTS Cross-sectional survey of a nationally representative sample of young people ( 2000 r and omly selected participants aged 12 - 25 years ) , via telephone interview , conducted in January-March 2008 . MAIN OUTCOME MEASURES Patterns of internet use including type of use , social networking , sources of information about mental health , alcohol or other substance use problems and levels of satisfaction with the information , and type of information accessed via websites . RESULTS Young people reported using the internet to connect with other young people ( 76.9 % ; 1464/1905 ) and to seek information about a mental health problem , regardless of whether they had a problem themselves ( 38.8 % ; 735/1894 ) . Twenty per cent of young people ( 398/1990 ) had personally experienced a mental health problem in the previous 5 years ; when these people were asked about sources of information used for this problem , 30.8 % ( 70/227 ) reported search ing the internet . Patterns of internet use and types of re sources used differed by age and sex . CONCLUSION Our findings suggest that technology is important in the everyday lives of young people , and online mental health services that encompass promotion and prevention activities should include a variety of re sources that appeal to all ages and both sexes , such as " question and answer " forums and email Guided by the Behavioral Vaccine Theory of prevention , this study uses a no-control group design to examine intervention variables that predict favorable changes in depressive symptoms at 6- to 8-week follow-up in at-risk adolescents who participated in a primary care , Internet-based prevention program . Participants included 83 adolescents from primary care setting s ages 14 to 21 ( M = 17.5 , SD = 2.04 ) , 56.2 % female , with 41 % non-White . Participants completed self-report measures , met with a physician , and then completed a 14-module Internet intervention targeting the prevention of depression . Linear regression models indicated that several intervention factors ( duration on website in days , the strength of the relationship with the physician , perceptions of ease of use , and the perceived relevance of the material presented ) were significantly associated with greater reductions in depressive symptoms from baseline to follow-up . Automatic negative thoughts significantly mediated the relation between change in depressive symptoms scores and both duration of use and physician relationship . Several intervention variables predicted favorable changes in depressive symptom scores among adolescents who participated in an Internet-based prevention program , and the strength of two of these variables was mediated by automatic negative thoughts . These findings support the importance of cognitive factors in preventing adolescent depression and suggest that modifiable aspects of technology-based intervention experience and relationships should be considered in optimizing intervention design PROBLEM Despite the increasing prevalence of mental health disorders in university students , few receive needed evidence -based treatment . OBJECTIVE The purpose of this study was to assess the feasibility and preliminary effects of a seven-session online cognitive-behavioral skill-building intervention ( i.e. , COPE , Creating Opportunities for Personal Empowerment ) versus a comparison group on their anxiety , depressive symptoms , and grade performance . METHODS A r and omized controlled pilot study was conducted from September 2012 to May 2013 with 121 college freshmen enrolled in a required one credit survey course . FINDINGS Although there were no significant differences in anxiety and depressive symptoms between the groups , only COPE students with an elevated level of anxiety at baseline had a significant decline in symptoms . Grade point average was higher in COPE versus comparison students . Evaluations indicated that COPE was a positive experience for students . CONCLUSIONS COPE is a promising brief intervention that can be integrated effectively into a required freshman course Background There have been no previous studies of the variables that predict adherence to online depression and anxiety intervention programs among adolescents . However , research of traditionally delivered intervention programs for a variety of health conditions in adolescence suggests that health knowledge , type and level of symptomatology , race , socioeconomic status , treatment setting , and support may predict adherence . Objective The aim was to compare adherence rates and identify the predictors of adherence to a cognitive behavior therapy website in two adolescent sample s that were offered the program in different setting s and under different conditions of support . Methods The first adolescent sample consisted of 1000 school students who completed the MoodGYM program in a classroom setting over five weeks as part of a r and omized controlled trial . The second sample consisted of 7207 adolescents who accessed the MoodGYM program spontaneously and directly through the open access URL . All users completed a brief survey before the start of the program that measured background characteristics , depression history , symptoms of depression and anxiety , and dysfunctional thinking . Results Adolescents in the school-based sample completed significantly more online exercises ( mean = 9.38 , SD = 6.84 ) than adolescents in the open access community sample ( mean = 3.10 , SD = 3.85 ; t 1088.62 = −28.39 , P < .001 ) . A multiple linear regression revealed that school-based setting ( P < .001 ) and female gender ( P < .001 ) were predictive of greater adherence , as were living in a rural area ( P < .001 ) and lower pre-test anxiety ( P = .04 ) scores for the school-based sample and higher pre-test depression scores ( P = .01 ) for the community sample . A history of depression ( P = .33 ) and pre-test warpy thoughts scores ( P = .35 ) were not predictive of adherence in the school-based or community sample . Conclusion Adherence is greater in monitored setting s , and the predictors of adherence differ between setting s. Underst and ing these differences may improve program effectiveness and efficiency OBJECTIVE This pilot r and omized controlled trial examined the effect of an online intervention for college students at risk for suicide , Electronic Bridge to Mental Health Services ( eBridge ) , which included personalized feedback and optional online counseling delivered in accordance with motivational interviewing principles . Primary outcomes were readiness to seek information or talk with family and friends about mental health treatment , readiness to seek mental health treatment , and actual treatment linkage . METHOD Participants were 76 college students ( 45 women , 31 men ; mean age = 22.9 years , SD = 5.0 years ) at a large public university who screened positive for suicide risk , defined by at least 2 of the following : suicidal thoughts , history of suicide attempt , depression , and alcohol abuse . Racial/ethnic self- identification s were primarily Caucasian ( n = 54 ) and Asian ( n = 21 ) . Students were r and omized to eBridge or the control condition ( personalized feedback only , offered in plain report format ) . Outcomes were measured at 2-month follow-up . RESULTS Despite relatively modest engagement in online counseling ( 29 % of students posted ≥1 message ) , students assigned to eBridge reported significantly higher readiness for help-seeking scores , especially readiness to talk to family , talk to friends , and see a mental health professional . Students assigned to eBridge also reported lower stigma levels and were more likely to link to mental health treatment . CONCLUSIONS Findings suggest that offering students personalized feedback and the option of online counseling , using motivational interviewing principles , has a positive impact on students ' readiness to consider and engage in mental health treatment . Further research is warranted to determine the robustness of this effect , the mechanism by which improved readiness and treatment linkage occurs , and the longer term impact on student mental health outcomes Little evidence exists regarding the efficacy of suicide prevention programmes among the youth . This pilot study aim ed to test the effects of a specifically design ed , eight‐module Internet‐based programme on suicidal ideation among secondary school students BACKGROUND Suicide-related behaviour is a major problem among adolescents . Yet relatively few studies have tested the efficacy , acceptability and safety of interventions for this population . We developed and pilot tested an online intervention for at-risk school students , which has led to reduced suicidal ideation , hopelessness and depressive symptoms . The aims of this study were to examine the safety and acceptability of the programme , and to determine which components were found to be most helpful and enjoyable . METHODS This pilot study employed a pre-test/post-test design , with an 8-week intervention phase . Participants were assessed immediately before , and immediately after the intervention . Participants were also asked to complete a weekly question naire immediately after the intervention , and again 2 days later assessing suicidal ideation and distress . RESULTS Twenty-one young people completed the intervention . Overall , the intervention did not lead to increases in suicidal ideation or distress . Participants reported enjoying the programme , in particular watching the video diaries and completing the activities , and said they would recommend the programme to a friend . Overall , the cognitive components of the programme were found to be most helpful . CONCLUSIONS Overall , the programme appeared to be a safe and acceptable intervention for at-risk adolescents . This was a small , pilot study so we need to interpret the results with caution . However , the findings are promising and suggest that young people at risk of suicide can safely be included in trials as long as adequate safety procedures are in place . The programme is now being tested in a r and omized controlled trial BACKGROUND Depressive disorder is common in adolescents and largely untreated . Computers offer a way of increasing access to care . Computerized therapy is effective for depressed adults but to date little has been done for depressed adolescents . AIMS The objective of this study was to examine the feasibility , acceptability , and effects of The Journey , a computerized cognitive behavioural therapy ( cCBT ) program for depressed adolescents . METHOD Thirty-four adolescents ( mean age 15.2 years , SD = 1.5 ) referred by school counsellors were r and omly assigned to either cCBT or a computer-administered attention placebo program with psychoeducational content ( CPE ) . Participants completed the intervention at school . Data were collected at baseline , post-intervention and at a 1-month follow-up . The primary outcome measure was the Child Depression Rating Scale Revised ( CDRS-R ) ; secondary outcome measures were : RADS-2 ; Pediatric Quality of Life Inventory ; Adolescent Coping Scale ( short form ) ; response and remission rates on CDRS-R. Completion rates and self-reported satisfaction ratings were used to assess feasibility and acceptabililty of the intervention . RESULTS Ninety-four percent of cCBT and 82 % of CPE participants completed the intervention . Eighty-nine percent liked The Journey a lot or thought it was " okay " and 89 % of them would recommend it for use with others as is or after some improvement . Adolescents treated with cCBT showed greater symptom improvement on CDRS-R than those treated with CPE program ( mean change on cCBT = 17.6 , CI = 14.13 - 21.00 ; CPE = 6.06 , CI = 2.01 - 10.02 ; p < .001 ) . CONCLUSIONS It is feasible , acceptable and efficacious to deliver computerized CBT to depressed adolescents in a school setting . Generalizability is limited by the size of the study AIM Implementation of targeted e-mental health interventions offers a promising solution to reducing the burden of disease associated with youth depression . A single-group pilot study was conducted to evaluate the acceptability , feasibility , usability and safety of a novel , moderated online social therapy intervention ( entitled Rebound ) for depression relapse prevention in young people . METHODS Participants were 42 young people ( 15 - 25 years ) ( 50 % men ; mean age = 18.5 years ) in partial or full remission . Participants had access to the Rebound platform for at least 12 weeks , including the social networking , peer and clinical moderator and therapy components . RESULTS Follow-up data were available for 39 ( 92.9 % ) participants . There was high system usage , with 3034 user logins ( mean = 72.2 per user ) and 2146 posts ( mean = 51.1 ) . Almost 70 % of users had ≥10 logins over the 12 weeks , with 78.5 % logging in over at least 2 months of the pilot . A total of 32 ( 84 % ) participants rated the intervention as helpful . There was significant improvement between the number of participants in full remission at baseline ( n = 5 ; none of whom relapsed ) relative to n = 19 at 12-week follow-up ( P < 0.001 ) . Six ( 14.3 % ) participants relapsed to full threshold symptoms at 12 weeks . There was a significant improvement to interviewer-rated depression scores ( Montgomery-Asberg Depression Rating Scale ( MADRS ) ; P = 0.014 , d = 0.45 ) and a trend for improved strength use ( P = 0.088 , d = 0.29 ) . The single-group design and 12-week treatment phase preclude a full underst and ing of the clinical benefits of the Rebound intervention . CONCLUSIONS The Rebound intervention was shown to be acceptable , feasible , highly usable and safe in young people with major depression Background Attrition is a persistent issue in online self-help programs , but limited research is available on reasons for attrition or successful methods for improving participant retention . One potential approach to underst and ing attrition and retention in such programs is to examine person-related variables ( eg , beliefs and attitudes ) that influence behavior . Theoretical models , such as the Theory of Planned Behavior , that describe conditions influencing human behavior may provide a useful framework for predicting participant retention in online-based program . Objective We examined predictors of participant retention in a guided online anxiety , depression , and stress self-help program for university students using the theory of planned behavior . We also explored whether age , symptom severity , and type of coaching ( ie , email vs phone ) affected participant retention . Methods 65 university students with mild to moderate depression , anxiety , and stress were enrolled in this prospect i ve cohort study . Participants completed a question naire based on the theory of planned behavior prior to commencing the online-based program and the Depression Anxiety and Stress Scale ( DASS ) during the assessment module of the program . Participant retention was operationalized as the number of program modules completed . Results Perceived control over completing the online program significantly predicted intention to complete the program ( F3,62=6.7 ; P=.001 ; adjusted R2=.2 ; st and ardized beta=.436 , P=.001 ) . Age ( st and ardized beta=.319 , P=.03 ) and perceived behavioral control ( st and ardized beta=.295 , P=.05 ) predicted the number of program modules completed ( F3,61=3.20 , P=.03 , adjusted R2 = .11 ) . Initial level of distress ( ie , symptom severity ) did not predict participant retention ( P=.55 ) . Participants who chose phone-based coaching completed more program modules than participants who chose email-based coaching ( Mann-Whitney ’s U=137 ; P=.004 ) . Conclusions Participants ’ age , level of perceived behavioral control , and choice of interaction ( ie , phone-based or email-based coaching ) were found to influence retention in this online-based program OBJECTIVE We developed a primary care/Internet-based intervention for adolescents at risk for depression ( CATCH-IT , Competent Adulthood Transition with Cognitive-behavioral , Humanistic and Interpersonal Training ) . This phase II clinical trial compares two forms of primary care provider ( PCP ) engagement ( motivational interview [ MI ] and brief advice [ BA ] ) for adolescents using the Internet program . METHOD ADOLESCENTS SCREENING POSITIVE FOR DEPRESSION WERE RECRUITED FROM PRIMARY CARE PRACTICE S AND R AND OMLY ASSIGNED TO A VERSION OF THE INTERVENTION : PCP MI + Internet program or PCP BA + Internet program . Between-group and within-group comparisons were conducted on depressive disorder outcome measures at baseline and one-year post-enrollment . Regression analyses examined factors predicting declines in depressed mood . RESULTS Both groups demonstrated significant within-group decreases in depressed mood , loneliness , and self-harm ideation . While no between-group differences were noted in depressed mood or depressive disorder measures at one-year , fewer participants in the MI group had experienced a depressive episode . Greater participant automatic negative thoughts and more favorable ratings of a component of the Internet-based training experience predicted declines in depressed mood at one-year . CONCLUSIONS A primary care/Internet-based intervention for depression prevention demonstrated sustained reductions in depressed mood , and , when coupled with motivational interviewing , reduction in the likelihood of being diagnosed with a depressive episode . This tool may help extend the services at the disposal of a primary care provider and can provide a bridge for adolescents at risk for depression prior to referral to mental health specialists PURPOSE To assess , from the young adults ' ( YAs ' ) perspectives , the critical parameters ( necessity , acceptability , feasibility , fidelity , and safety ) of an avatar-based intervention , eSMART-MH , to reduce depressive symptoms . DESIGN AND METHODS YAs ( n = 60 ) were r and omly assigned to eSMART-MH or control and observed for 12 weeks . Qualitative and quantitative data were collected . FINDINGS Necessity , acceptability , fidelity , and safety of eSMART-MH were supported . Feasibility results were mixed . When benchmarked against usual care , eSMART-MH demonstrated greater feasibility . PRACTICE IMPLICATION S eSMART-MH is a promising digital therapeutic for depressive symptoms . Feasibility can be strengthened through " on the go " access via mobile devices and Internet delivery Objective Anxiety and depression are highly prevalent disorders in adolescence . They are associated with deficits in working memory ( WM ) , which also appears to increase rumination , worry , and negative mood . WM training , especially in an emotional context , might help in reducing or preventing these disorders . The current study investigated the direct effects of online emotional WM training on WM capacity , and short‐ and long‐term effects on symptoms of anxiety and depression , and secondary measures of emotional functioning . Methods Unselected adolescents ( n = 168 , aged 11–18 ) were r and omised over an active or placebo emotional WM training . WM was assessed before and after 4 weeks of bi‐weekly training . Emotional functioning was assessed pre‐ and post‐training and at 3 , 6 , and 12 months follow‐up . Results Improvements in WM capacity and both short‐ and long‐term emotional functioning were found in both training groups , with the only group difference being a trend for a larger increase in self‐esteem in the active group compared to the placebo group . Conclusions The general improvements irrespective of training condition suggest non‐specific training or time effects , or some shared active ingredient in both conditions . Future research is necessary to detect potentially effective components of ( emotional ) WM training and to increase adolescent engagement with online training |
11,150 | 29,297,205 | Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months ( FVC % MD -0.82 , 95 % CI -3.95 to 2.31 ; P = 0.61 ; two trials , 149 participants ; DLCO % MD -1.41 , 95 % CI -10.40 to 7.58 ; P = 0.76 ; two trials , 149 participants ) .Risk of side effects was increased with cyclophosphamide versus mycophenolate , in particular , leukopenia and thrombocytopenia .
The data demonstrates no significant impact on health-related quality of life , all-cause mortality , dyspnoea , or cough severity in the cyclophosphamide group compared with the mycophenolate group .
No trials reported outcomes associated with functional exercise tests .
This review , which is based on studies of varying method ological quality , demonstrates that overall , in this population , small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo , but not of the difference in % DLCO , or when compared with mycophenolate .
Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide .
Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC . | BACKGROUND Approximately one-third of individuals with interstitial lung disease ( ILD ) have associated connective tissue disease ( CTD ) .
The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis ( SSc ) , rheumatoid arthritis , polymyositis/dermatomyositis , and Sjögren 's syndrome .
Although many people with CTD-ILD do not develop progressive lung disease , a significant proportion do progress , leading to reduced physical function , decreased quality of life , and death .
ILD is now the major cause of death amongst individuals with systemic sclerosis .
Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses .
However this comes with potential toxicities , including nausea , haemorrhagic cystitis , bladder cancer , bone marrow suppression , increased risk of opportunistic infections , and haematological and solid organ malignancies .
Decision-making in the treatment of individuals with CTD-ILD is difficult ; the clinician needs to identify those who will develop progressive disease , and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy , for which only relatively limited data on efficacy can be found .
Similarly , it is not clear whether histological subtype , disease duration , or disease extent can be used to predict treatment responsiveness .
OBJECTIVES To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD . | Background Decline in forced vital capacity ( FVC ) over time reliably predicts mortality in patients with idiopathic pulmonary fibrosis . The use of this measure in clinical practice is recommended by current evidence -based guidelines . It is unknown if the method of calculating decline in FVC ( relative vs absolute change ) impacts its frequency or its ability to predict mortality . Methods Patients with idiopathic pulmonary fibrosis from two prospect i ve cohorts were included if they had a baseline and 12-month follow-up FVC . A ≥10 % decline in FVC from baseline was calculated in two ways : a relative decline of 10 % ( eg , from 60 % predicted to 54 % predicted ) and an absolute decline of 10 % ( eg , from 60 % predicted to 50 % predicted ) . The frequency of a ≥10 % decline in FVC and its ability to predict 2-year transplant-free survival were compared between these two methods . Declines in FVC of ≥5 % and ≥15 % were similarly compared . Analyses were performed unadjusted and adjusted for age , gender , use of oxygen , baseline FVC and baseline diffusion capacity for carbon monoxide . Results The frequency of any given FVC decline was significantly greater using the relative change in FVC method . For ≥10 % decline , both methods predicted 2-year transplant-free survival with similar accuracy , and remained significant predictors after adjusting for baseline characteristics . The absolute change method appeared more predictive for ≥5 % decline . Conclusions Using the relative change in FVC maximises the chance of identifying a ≥10 % decline in FVC without sacrificing prognostic accuracy . This may not hold true for ≥5 % decline in FVC . These findings have important implication s for clinical practice and the design of clinical trials OBJECTIVE Patients with systemic sclerosis-associated interstitial lung disease ( SSc-ILD ) are thought to have the greatest decline in lung function ( forced vital capacity [FVC]% predicted ) in the early years after disease onset . The aim of this study was to assess the natural history of the decline in FVC% predicted in patients receiving placebo in the Scleroderma Lung Study and to evaluate possible factors for cohort enrichment in future therapeutic trials . METHODS Patients r and omized to receive placebo ( n=79 ) were divided into 3 groups based on the duration of SSc ( 0 - 2 years , 2 - 4 years , and > 4 years ) . Descriptive statistics and a mixed-effects model were used to analyze the rate of decline in the FVC% predicted over a 1-year period . Additional analyses stratified according to the severity of fibrosis on high-resolution computed tomography ( H RCT ) were performed , and interactions between disease severity and disease duration were explored . RESULTS The mean±SD decline in the unadjusted FVC% predicted during the 1-year period was 4.2±12.8 % . At baseline , 28.5 % , 43.0 % , and 28.5 % of patients were in the groups with disease duration s of 0 - 2 years , 2 - 4 years , and > 4 years , respectively . The rate of decline in the FVC% predicted was not significantly different across the 3 disease groups ( P=0.85 ) . When stratified by baseline fibrosis on H RCT , the rate of decline in the FVC% predicted was statistically significantly greater in the group with severe fibrosis ( mean annualized decline in the FVC% predicted 7.2 % versus 2.7 % in the groups with no or moderate fibrosis ; P=0.008 ) . The decline observed in the group with severe fibrosis was most pronounced in those with a relatively short disease duration ( 0 - 2 years ; annualized decline 7.0 % ) . CONCLUSION Among patients with SSc-ILD in the Scleroderma Lung Study , the rates of progression of lung disease were similar irrespective of disease duration . The baseline H RCT fibrosis score is a predictor of a future decline in the FVC% predicted in the absence of effective treatment Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis . We undertook a r and omised , controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis , and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations . 65 patients ( 60 female , 5 male ; median [ range ] age 29 [ 10 - 48 ] years ) with severe lupus nephritis were assigned r and omly to monthly pulse methylprednisolone for 6 months ( 25 patients ) , monthly pulse cyclophosphamide for 6 months ( 20 ) , or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years ( 20 ) . Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide ( p less than 0.04 ) . Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide . However , patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide ( p less than 0.01 ) . An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis . Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations OBJECTIVE The lack of r and omized controlled trials ( RCTs ) in pulmonary fibrosis in systemic sclerosis ( SSc ) has hampered an evidence -based approach to treatment . This RCT was undertaken to investigate the effects of intravenous ( IV ) cyclophosphamide ( CYC ) followed by azathioprine ( AZA ) treatment in pulmonary fibrosis in SSc . METHODS Forty-five patients were r and omized to receive low-dose prednisolone and 6 infusions ( monthly ) of CYC followed by oral AZA , or placebo . Primary outcome measures were change in percent predicted forced vital capacity ( FVC ) and change in single-breath diffusing capacity for carbon monoxide ( DLCO ) . Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores . An intent-to-treat statistical analysis was performed . RESULTS At baseline , there were no significant group differences in factors linked to outcome , including severity of pulmonary fibrosis and autoantibody status . Sixty-two percent of the patients completed the first year of treatment . Withdrawals included 9 patients ( 6 from the placebo group ) with significant decline in lung function , 2 with treatment side effects ( both from the active treatment group ) , and 6 with non-trial-related comorbidity . No hemorrhagic cystitis or bone marrow suppression was observed . Estimation of the relative treatment effect ( active treatment versus placebo ) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19 % ; this between-group difference showed a trend toward statistical significance ( P = 0.08 ) . No improvements in DLCO or secondary outcome measures were identified . CONCLUSION This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo . However , for FVC there was a trend toward statistical significance between the 2 groups . This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease . Therapy was well tolerated with no increase in serious adverse events Introduction The objective of the present study was to examine the association of baseline demographic and clinical characteristics with sequentially obtained measurements of forced vital capacity ( FVC ) , expressed as a percentage of the predicted value , and to identify predictors of the decline rate in FVC over time in the Genetics versus Environment in Scleroderma Outcome Study ( GENISOS ) . Methods To date , 266 patients have been enrolled in GENISOS , a prospect i ve , observational cohort of patients with early systemic sclerosis . In addition to pulmonary function tests ( PFTs ) , clinical and laboratory data were obtained from each patient . We analyzed 926 FVC measurements utilizing generalized linear mixed models . The predictive significance of baseline variables for the decline rate in FVC was investigated by the interaction term between the variable and the follow-up time within the first 3 years after enrollment as well as throughout the entire follow-up time . Results The cohort consisted of 125 white , 54 African American , and 77 Hispanic patients with average disease duration of 2.5 years at enrollment . The mean follow-up time was 3.8 years , ranging up to 11.4 years . A number of baseline variables , including antibody status , African American ethnicity , disease type , baseline PFT values , modified Rodnan Skin Score , fibrosis on chest radiograph , and lung and skin subscores of the Severity Index , were associated with serially measured FVC levels . However , only the presence of anti-topoisomerase I antibodies ( ATA ) was associated with lower FVC levels ( P < 0.001 ) as well as accelerated decline rate in FVC within the first 3 years of follow-up ( P = 0.02 ) . None of the baseline variables predicted the rate of decline in FVC on long-term follow-up . Patients with rapidly progressive ILD , however , were under-represented in the long-term follow-up group because the accelerated rate of decline in FVC was associated with poor survival ( P = 0.001 ) . Conclusions Presence of ATA was the only baseline variable associated with differential FVC levels , predicting the rate of decline in FVC within the first 3 years of follow-up . The association of faster decline in FVC with poor survival further emphasizes the need for identification of predictive biomarkers by collection of genetic information and serial blood sample s in cohort studies Objective : To estimate minimally important differences ( MIDs ) in scores for the modified Rodnan Skin Score ( mRSS ) and Health Assessment Question naire — Disability Index ( HAQ-DI ) in a clinical trial on diffuse systemic sclerosis ( SSc ) . Participants and methods : 134 people participated in a 2-year , double-blind , r and omised clinical trial comparing efficacy of low-dose and high-dose d-penicillamine in diffuse SSc . At 6 , 12 , 18 and 24 months , the investigator was asked to rate the change in the patient ’s health since entering the study : markedly worsened , moderately worsened , slightly worsened , unchanged , slightly improved , moderately improved or markedly improved . Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved . Results : The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 ( 0.40–0.66 effect size ) and for the HAQ-DI from 0.10 to 0.14 ( 0.15–0.21 effect size ) . Patients who were rated to improve more than slightly were found to improve by 6.9–14.2 ( 0.86–1.77 effect size ) on the mRSS and 0.21–0.55 ( 0.32–0.83 effect size ) on the HAQ-DI score . Conclusion : MID estimates are provided for improvement in the mRSS and HAQ-DI scores , which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc Background The assessment of treatment response in idiopathic pulmonary fibrosis ( IPF ) is complicated by the variable clinical course . We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment . Methods The source population included patients enrolled in the ASCEND and CAPACITY trials ( N=1247 ) . Pearson 's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population . Outcomes following a ≥10 % decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10 % decline in FVC or death during the subsequent 6 months . Results A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population ( coefficient , −0.146 , p<0.001 ) , indicating substantial variability . Thirty-four ( 5.5 % ) and 68 ( 10.9 % ) patients in the pirfenidone and placebo groups , respectively , experienced a ≥10 % decline in FVC by month 6 . During the subsequent 6 months , fewer patients in the pirfenidone group compared with placebo experienced a ≥10 % decline in FVC or death ( 5.9 % vs 27.9 % ; relative difference , 78.9 % ) . There was one ( 2.9 % ) death in the pirfenidone group and 14 ( 20.6 % ) deaths in the placebo group ( relative difference , 85.7 % ) . Conclusions Longitudinal FVC data from patients with IPF showed substantial intrasubject variability , underscoring the inability to reliably assess therapeutic response using serial FVC trends . In patients who progressed during treatment , continued treatment with pirfenidone result ed in a lower risk of subsequent FVC decline or death . Trial registration numbers NCT01366209 , NCT00287729 , NCT00287716 OBJECTIVES To assess the safety and efficacy of long-term treatment with rituximab ( RTX ) in patients with systemic sclerosis ( SSc ) . METHODS Eight patients with SSc-associated interstitial lung disease ( ILD ) received 4 cycles of RTX and had a follow-up of 2 years . Lung involvement was assessed by pulmonary function tests and chest H RCT . Skin involvement was assessed both clinical ly and histologically . RESULTS We found a linear improvement of lung function and skin thickening over the 2 years of RTX treatment . There was a significant increase of FVC at 2 years compared to baseline ( mean ± SEM : 77.13±7.13 vs. 68.13±6.96 , respectively , p<0.0001 ) . Similarly , DLco increased significantly at 2 years compared to baseline ( mean ± SEM : 63.13±7.65 vs. 52.25±7.32 , respectively , p<0.001 ) . Skin thickening , assessed with the MRSS , improved significantly at 2 years compared to baseline ( mean ± SEM : 4.87±0.83 vs. 13.5±2.42 , respectively , p<0.0001 ) . A reduction in myofibroblast score was seen histologically following RTX treatment . CONCLUSIONS Our results indicate that long-term treatment with RTX may favourably affect lung function and skin fibrosis in patients with SSc . Larger scale , multicentre , r and omised , controlled studies are needed to further explore the efficacy of RTX in SSc BACKGROUND We conducted a double-blind , r and omized , placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease . METHODS At 13 clinical centers throughout the United States , we enrolled 158 patients with scleroderma , restrictive lung physiology , dyspnea , and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid , thoracic high-resolution computed tomography , or both . Patients received oral cyclophosphamide ( < or = 2 mg per kilogram of body weight per day ) or matching placebo for one year and were followed for an additional year . Pulmonary function was assessed every three months during the first year , and the primary end point was the forced vital capacity ( FVC , expressed as a percentage of the predicted value ) at 12 months , after adjustment for the baseline FVC . RESULTS Of 158 patients , 145 completed at least six months of treatment and were included in the analysis . The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent ( 95 percent confidence interval , 0.28 to 4.79 percent ) , favoring cyclophosphamide ( P<0.03 ) . There were also treatment-related differences in physiological and symptom outcomes , and the difference in FVC was maintained at 24 months . There was a greater frequency of adverse events in the cyclophosphamide group , but the difference between the two groups in the number of serious adverse events was not significant . CONCLUSIONS One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function , dyspnea , thickening of the skin , and the health-related quality of life . The effects on lung function were maintained through the 24 months of the study OBJECTIVE To prospect ively study the clinical features , pathophysiology , treatment and prognosis of Wegener granulomatosis . DESIGN Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years , 158 have been followed for 6 months to 24 years ( a total of 1229 patient-years ) . MEASUREMENTS Characteristics of clinical presentation , surgical pathology , course of illness , laboratory and radiographic findings , and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system . SETTING The Warren Magnuson Clinical Center of the National Institutes of Health . MAIN RESULTS Men and women were equally represented ; 97 % of patients were white , and 85 % were more than 19 years of age . The mean period of follow-up was 8 years . One hundred and thirty-three patients ( 84 % ) received " st and ard " therapy with daily low-dose cyclophosphamide and glucocorticoids . Eight ( 5.0 % ) received only low-dose cyclophosphamide . Six ( 4.0 % ) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids . Ten patients ( 6.0 % ) were treated with only glucocorticoids . Ninety-one percent of patients experienced marked improvement , and 75 % achieved complete remission . Fifty percent of remissions were associated with one or more relapses . Of 99 patients followed for greater than 5 years , 44 % had remissions of greater than 5 years duration . Thirteen percent of patients died of Wegener granulomatosis , treatment-related causes , or both . Almost all patients had serious morbidity from irreversible features of their disease ( 86 % ) or side effects of treatment ( 42 % ) . CONCLUSIONS The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids . Nonetheless , disease- and treatment-related morbidity is often profound . Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment . Despite continued therapeutic success with cyclophosphamide , our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity result ing from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens BACKGROUND Cough is a significant symptom in patients with scleroderma interstitial lung disease ( SSc-ILD ) , affecting 73 % of the 158 patients enrolled in the Scleroderma Lung Study ( SLS ) , a multicenter r and omized trial of oral cyclophosphamide ( CYC ) vs placebo ( PLA ) in patients with active interstitial lung disease . METHODS We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA . RESULTS Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide , dyspnea , the quality -of-life physical component summary , and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline . Cough severity and frequency correlated with FVC % predicted . After 12 months of treatment , cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months ( 6 months after discontinuation of CYC ) . However , the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group . Treatment-related improvements in cough frequency , as well as in FVC , were no longer apparent 12 months after discontinuation of CYC . CONCLUSIONS Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis . Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment . Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT000004563 ; URL : www . clinical BACKGROUND The Scleroderma Lung Study ( SLS ) demonstrated significant treatment-associated improvements in pulmonary function and symptoms when patients with scleroderma-related interstitial lung disease ( SSc-ILD ) were treated with a 1-year course of cyclophosphamide ( CYC ) in a r and omized , double-blinded , placebo-controlled clinical trial . This study examined thoracic high-resolution CT ( H RCT ) scans obtained during the SLS for treatment-associated changes over time . METHODS Ninety-eight of the 158 subjects ( CYC group , 49 subjects ; placebo group , 49 subjects ) participating in the SLS underwent thoracic H RCT scans both at baseline and after 12 months of treatment , which were available for analysis . Two independent radiologists visually scored the baseline H RCT scans for the presence of ground-glass opacities ( GGOs ) , fibrosis ( FIB ) , and honeycomb cysts ( HCs ) on a scale of 0 to 4 . The treatment effect at 12 months was assessed by a blinded comparison of baseline and follow-up scans for evidence of stability and improvement ( not worse ) or deterioration ( worse ) . RESULTS At the end of treatment , FIB was significantly worse in the placebo treatment group than in the CYC treatment group ( p = 0.014 ) . Furthermore , differences in the 12-month change in FIB between the CYC and placebo groups correlated significantly with other outcome measures , including the 12-month changes in FVC ( p < 0.05 ) , total lung capacity ( p < 0.05 ) , and dyspnea ( p < 0.001 ) scores . However , no differences were noted between the two groups with respect to changes in either GGOs or HCs . CONCLUSIONS A 1-year course of treatment of SSc-ILD with CYC was associated with treatment-related changes in FIB scores on H RCT scans , which correlated with other measures of treatment response . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00004563 RATIONALE In interstitial lung disease complicating systemic sclerosis ( SSc-ILD ) , the optimal prognostic use of baseline pulmonary function tests ( PFTs ) and high-resolution computed tomography ( H RCT ) is uncertain . OBJECTIVES To construct a readily applicable prognostic algorithm in SSc-ILD , integrating PFTs and H RCT . METHODS The prognostic value of baseline PFT and H RCT variables was quantified in patients with SSc-ILD ( n = 215 ) against survival and serial PFT data . MEASUREMENTS AND MAIN RESULTS Increasingly extensive disease on H RCT was a powerful predictor of mortality ( P < 0.0005 ) , with an optimal extent threshold of 20 % . In patients with H RCT extent of 10 - 30 % ( termed indeterminate disease ) , an FVC threshold of 70 % was an adequate prognostic substitute . On the basis of these observations , SSc-ILD was staged as limited disease ( minimal disease on H RCT or , in indeterminate cases , FVC > or= 70 % ) or extensive disease ( severe disease on H RCT or , in indeterminate cases , FVC < 70 % ) . This system ( hazards ratio [ HR ] , 3.46 ; 95 % confidence interval [ CI ] , 2.19 - 5.46 ; P < 0.0005 ) was more discriminatory than an H RCT threshold of 20 % ( HR , 2.48 ; 95 % CI , 1.57 - 3.92 ; P < 0.0005 ) or an FVC threshold of 70 % ( HR , 2.11 ; 95 % CI , 1.34 - 3.32 ; P = 0.001 ) . The system was evaluated by four trainees and four practitioners , with minimal and severe disease on H RCT defined as clearly < 20 % or clearly > 20 % , respectively , and the use of an FVC threshold of 70 % in indeterminate cases . The staging system was predictive of mortality for all scorers , with prognostic separation higher for practitioners ( HR , 3.39 - 3.82 ) than trainees ( HR , 1.87 - 2.60 ) . CONCLUSIONS An easily applicable limited/extensive staging system for SSc-ILD , based on combined evaluation with H RCT and PFTs , provides discriminatory prognostic information Therapy for patients with life-threatening systemic lupus erythematosus has included high doses of corticosteroids and cytotoxic or cytostatic drugs [ 1 - 20 ] . Cyclophosphamide , given in intermittent intravenous boluses , has been widely used to treat renal [ 1 - 68 , 15 , 21 ] and central nervous system disease [ 2 , 3 , 6 , 7 , 19 - 21 ] , but this therapy is sometimes withheld in the hope that disease might be controlled with corticosteroids or other immunosuppressive drugs . Moreover , some patients do not respond adequately to therapy with intermittent boluses of cyclophosphamide , and these patients might benefit from more intensive therapy . In a previous study [ 3 ] , monthly administration of methylprednisolone ( 1.0 g/m2 body surface area ) was less effective than bolus therapy with cyclophosphamide . However , the limited duration of the methylprednisolone regimen [ 6 months ] might have been insufficient to treat lupus nephritis . To address this concern , we evaluated patients receiving methylprednisolone once a month for 1 year ; additional boluses were given as needed to control disease . We compared these patients with patients receiving our st and ard therapy : intermittent boluses of cyclophosphamide . A group of patients r and omly assigned to receive both cyclophosphamide and methylprednisolone was also included for three major reasons : 1 ) some patients with lupus nephritis respond inadequately to boluses of cyclophosphamide , 2 ) anecdotal experience had suggested that cyclophosphamide therapy might be more effective for all patients when given with substantial doses of corticosteroids , and 3 ) animal studies had shown the advantage of combined chemotherapy for lupus nephritis [ 22 , 23 ] . Our study design was modified from previous design s so that therapy could be intensified for patients with refractory or relapsing disease . Methods Patient Selection We enrolled 82 patients with lupus nephritis into this r and omized , parallel study at the Clinical Center of the National Institutes of Health ( Bethesda , Maryl and ) between 1986 and 1990 . To enter the study , patients had to have both glomerulonephritis and a diagnosis of systemic lupus erythematosus [ 24 ] . Glomerulonephritis was defined as a sediment on two or more urinalyses that showed either 10 or more erythrocytes per high-power field or erythrocyte or leukocyte casts ( without evidence of infection ) or both , plus histologic evidence of active proliferative lupus glomerulonephritis on a renal biopsy specimen obtained within 3 months of study entry ( provided that a biopsy could be done safely ) . Scores for renal histologic activity and chronicity were assessed as reported elsewhere [ 25 ] . All eligible patients were invited to participate . Exclusion criteria were 1 ) receipt of cytotoxic drug treatment for more than 2 weeks during the 6 weeks before study entry or receipt of cyclophosphamide therapy for more than 10 weeks at any time ; 2 ) receipt of pulse therapy with corticosteroids during the 6 weeks before study entry ; 3 ) need [ at the time of study entry ] for oral corticosteroids in dosages greater than 0.5 mg of a prednisone equivalent per kilogram of body weight per day to control extrarenal disease ; 4 ) active or chronic infection ; 5 ) pregnancy ; 6 ) the presence of only one kidney ; 7 ) insulin-dependent diabetes mellitus ; and 8) allergy to methylprednisolone or cyclophosphamide . Study Design The protocol that we used was approved by the NIDDK/NIAMS ( National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Arthritis and Musculoskeletal and Skin Diseases ) Institutional Review Board [ 86-AR-0189 ] . After giving signed , written informed consent , patients were r and omly assigned to one of three treatment groups by drawing from a masked card sequence arranged from a table of r and om numbers . Each group received one of the following regimens : 1 ) intravenous methylprednisolone [ 1 g/m2 body surface area ] , given as boluses over 60 minutes on 3 consecutive days followed by at least 12 consecutive monthly single infusions ; 2 ) intravenous cyclophosphamide , given as boluses once a month for 6 consecutive months and then once every 3 months for at least 2 more years ; and 3 ) the combination of these two regimens . After a patient completed 1 year of study , a decision about whether therapy would be modified was made on the basis of the patient 's renal status at that time ( Figure 1 ) . In patients receiving methylprednisolone , therapy was discontinued if urine studies showed that renal remission had occurred . Renal remission was defined as the presence of fewer than 10 dysmorphic erythrocytes per high-power field , the absence of cellular casts , and excretion of less than 1 g of protein per day . If a renal remission was not evident , the patient continued to receive methylprednisolone every month for 6 more months . After the additional 6 months , if renal remission was still not evident , the patient received treatment for another 6 months . Therapy with methylprednisolone was limited to a maximum of 36 monthly boluses . Figure 1 . Treatment regimens and decision pathways used in this clinical trial for lupus nephritis . At 1 year , patients who had been receiving cyclophosphamide alone or in combination with methylprednisolone continued to receive or began to receive cyclophosphamide alone , once every 3 months , if the results of urine studies were substantially improved . Substantial improvement was defined as a reduction of at least 50 % in 1 ) the number of dysmorphic erythrocytes seen in urine sample s , 2 ) the number of cellular casts , and 3 ) proteinuria , without a mmol of the serum creatinine level . Quarterly administration of cyclophosphamide was continued for 2 years after renal remission occurred , after which time therapy was stopped . After the first year of the study , patients in any treatment group who were no longer receiving monthly therapy but who had evidence of the reactivation of glomerular disease had their originally assigned regimens reinstituted as if they were beginning therapy from enrollment . Reactivation of glomerular disease was defined as new active nephritis with an increase of at least 50 % ( relative to the lowest reproducible values obtained during the study ) in at least two of the following : number of dysmorphic erythrocytes ( 10 per high-power field ) , number of cellular casts , proteinuria ( 1 g of protein per day ) , or serum creatinine level . One year after the reinstitution of therapy , patients were again evaluated for evidence of active glomerulonephritis ( as described above ) . As before , patients could be withdrawn from therapy , could restart treatment , or could continue to receive cyclophosphamide every 3 months . Patients could restart therapy no more than twice ; if therapy failed more than three times , patients were declared to be nonresponders . Treatment and Follow-up Cyclophosphamide was infused for 60 minutes at an initial dose of 0.75 g/m2 body surface area . If the leukocyte nadir was greater than 3000 cells/mm3 , the cyclophosphamide dose was increased by 25 % , to a maximum of 1 g/m2 body surface area . The dose was reduced by 25 % for leukocyte counts less than 1500 cells/mm3 . Patients with a creatinine clearance of less than 30 mL/min received an initial dose of 0.5 g/m2 body surface area , and subsequent doses were adjusted on the basis of the lowest leukocyte count . Patients treated with cyclophosphamide were hydrated , and diuretics were used to maintain neutral fluid balance . Thiethylperazine , 10 mg , with 25 mg of diphenhydramine or 0.25 mg of lorazepam , was administered orally or intravenously every 6 hours for nausea . After the middle of 1990 , patients were treated in a day hospital setting , where they received intravenous saline , 200 mL per hour for 10 hours . Mesna ( 2-mercaptoethanesulfonate ) , at 20 % of the cyclophosphamide dose , was infused intravenously for 10 minutes before cyclophosphamide was administered and every 3 hours thereafter , for a total of four doses . Ondansetron , 8 mg , was given every 4 hours beginning 4 hours after infusion of cyclophosphamide , for a total of three doses . Dexamethasone , 10 mg , was given 4 hours after administration of cyclophosphamide [ 26 ] . Patients were instructed to continue oral hydration after discharge from the day hospital to maintain a dilute and frequent diuresis for at least 24 hours after infusion of cyclophosphamide . All patients were initially given oral prednisone , 0.5 mg/kg per day for 4 weeks . The prednisone dose was then tapered by 5 mg every other day each week to the minimal dose required to control extrarenal disease or 0.25 mg/kg every other day , whichever was greater . For severe extrarenal flares of lupus , patients were permitted to receive prednisone , 1.0 mg/kg per day for 2 weeks . Blood pressure was closely monitored and was maintained within 110 to 130/70 to 85 mm Hg with antihypertensive therapy . The intervals at which patients were followed were dictated by the activity of lupus and nephritis . In general , all patients were seen monthly during the first year of the study and every 3 months thereafter . At each study visit , patients were question ed about and examined for adverse events . Outcome Measures The primary study outcome was the response to the study drugs as defined by 1 ) the percentage of patients who achieved renal remission , 2 ) the number of nonresponders ( nonresponse was defined as 10 erythrocytes per high-power field , cellular casts , proteinuria [ > 1 g of protein per day ] , and doubling of the serum creatinine level ) , and 3 ) the percentage of adverse events . The outcome data , with the exception of data on adverse events , were collected in a blinded manner on 1 May 1995 , 5 years after the last patient was enrolled in the study . Secondary outcome measures were renal failure that required dialysis ( end-stage renal disease ) , stable doubling of the serum creatinine level , and number of renal relapses ( renal relapse was defined as a reactivation of renal disease after 6 or more months of RATIONALE The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease . OBJECTIVES To evaluate whether lavage cellularity identifies distinct subsets of disease and /or predicts cyclophosphamide responsiveness . METHODS Patients underwent baseline lavage and /or high-resolution computed tomography as part of a r and omized placebo-controlled trial of cyclophosphamide versus placebo ( Scleroderma Lung Study ) to determine the effect of therapy on forced vital capacity . Patients with 3 % or greater polymorphonuclear and /or 2 % or greater eosinophilic leukocytes on lavage and /or ground-glass opacification on computed tomography were eligible for enrollment . MEASUREMENTS AND MAIN RESULTS Lavage was performed in 201 individuals , including 141 of the 158 r and omized patients . Abnormal cellularity was present in 101 of these cases ( 71.6 % ) and defined a population with a higher percentage of men ( P = 0.04 ) , more severe lung function , including a worse forced vital capacity ( P = 0.003 ) , worse total lung capacity ( P = 0.005 ) and diffusing capacity of the lung for carbon monoxide ( P = 0.004 ) , more extensive ground-glass opacity ( P = 0.005 ) , and more extensive fibrosis in the right middle lobe ( P = 0.005 ) . Despite these relationships , the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year ( P = not significant ) . CONCLUSIONS The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response . Clinical trial registered with www . clinical trials.gov ( NCT 000004563 ) BACKGROUND Lung disease has become the leading cause of mortality and morbidity in scleroderma ( SSc ) patients . The frequency , nature , and progression of interstitial lung disease seen on high-resolution CT ( H RCT ) scans in patients with diffuse SSc ( dcSSc ) compared with those with limited SSc ( lcSSc ) has not been well characterized . METHODS Baseline H RCT scan images of 162 participants r and omized into a National Institutes of Health-funded clinical trial were compared to clinical features , pulmonary function test measures , and BAL fluid cellularity . The extent and distribution of interstitial lung disease H RCT findings , including pure ground-glass opacity ( pGGO ) , pulmonary fibrosis ( PF ) , and honeycomb cysts ( HCs ) , were recorded in the upper , middle , and lower lung zones on baseline and follow-up CT scan studies . RESULTS H RCT scan findings included 92.9 % PF , 49.4 % pGGO , and 37.2 % HCs . There was a significantly higher incidence of HCs in the three zones in lcSSc patients compared to dcSSc patients ( p = 0.034 , p = 0.048 , and p = 0.0007 , respectively ) . The extent of PF seen on H RCT scans was significantly negatively correlated with FVC ( r = - 0.22 ) , diffusing capacity of the lung for carbon monoxide ( r = - 0.44 ) , and total lung capacity ( r = - 0.36 ) . A positive correlation was found between pGGO and the increased number of acute inflammatory cells found in BAL fluid ( r = 0.28 ) . In the placebo group , disease progression was assessed as 30 % in the upper and middle lung zones , and 45 % in the lower lung zones . No difference in the progression rate was seen between lcSSc and dcSSc patients . CONCLUSIONS PF and GGO were the most common H RCT scan findings in symptomatic SSc patients . HCs were seen in more than one third of cases , being more common in lcSSc vs dcSSc . There was no relationship between progression and baseline PF extent or lcSSc vs dcSSc . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00004563 OBJECTIVE To determine whether baseline self- assessment measures of health status and physiologic indices of disease severity in alveolitis-positive patients with systemic sclerosis ( SSc ) correlate with the severity of their dyspnea , and to quantify functional impairment in patients with scleroderma lung disease and compare it with that in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS SSc patients ( n = 138 ) with diffuse ( n = 81 ) or limited ( n = 57 ) cutaneous disease and active alveolitis ( determined by bronchoalveolar lavage and /or high-resolution computed tomography ) who participated in the National Heart , Lung , and Blood Institute-sponsored , multicenter , parallel-group , double-blind , r and omized , placebo-controlled trial of oral cyclophosphamide for treatment of SSc-associated interstitial lung disease were evaluated . Pearson 's univariate correlations were determined between the Short Form 36 ( SF-36 ) physical component summary ( PCS ) and mental component summary ( MCS ) scales , functional question naires , and physiologic parameters of breathing ( forced vital capacity [ FVC ] and single-breath diffusing capacity for carbon monoxide [ DLCO ] ) . Student 's t-test was used to compare subgroups . Scores from 2 instruments for self- assessment of breathlessness , Mahler 's baseline dyspnea index ( BDI ) and a visual analog scale ( VAS ) for breathing , were divided at the median . Values for the DLCO and FVC ( % predicted ) were divided based on the American Thoracic Society guidelines for mild ( > 70 % of predicted ) , moderate ( 50 - 70 % of predicted ) , and severe ( < 50 % of predicted ) physiologic impairment . RESULTS Scores on the BDI and VAS for breathing were highly correlated ( r = -0.61 ) . The PCS and MCS were able to differentiate patients with more breathlessness ( measured by BDI and VAS for breathing ) and more abnormal physiologic measures ( FVC and DLCO ) . In SSc patients with alveolitis , all 8 domains of the SF-36 were significantly impaired as compared with the healthy population and were similar to those reported by patients with COPD . CONCLUSION The SF-36 was able to discriminate between scleroderma lung disease patients with more severe and less severe breathlessness , the primary symptom of active alveolitis . The SF-36 complements the BDI and VAS scores for breathing in scleroderma lung disease and is variably correlated with results of pulmonary function tests , suggesting that the SF-36 should be included as an outcome measure in intervention trials in this population Interstitial lung disease ( ILD ) is a common manifestation of systemic sclerosis ( SSc ) that may be responsible for severe restrictive lung disease and represents one of the two main causes of disease-related death in SSc patients . Since 1993 , the beneficial effect of oral or intravenous cyclophosphamide ( CYC ) in the treatment of SSc-related ILD has been reported in retrospective studies , one study showing improvement of pulmonary function test scores and /or chest computed tomography at 1 year and improvement of survival at 16 months . The results of two controlled trials were recently reported . The Scleroderma Lung Study , a prospect i ve r and omized placebo-controlled trial , included 158 patients of whom 145 completed at least 6 months of treatment . The course of forced vital capacity ( primary outcome ) adjusted at 1 year was significantly better in the group treated with oral CYC ( P < 0.03 ) , although the effect of CYC was minor . The Fibrosing Alveolitis in Scleroderma Trial ( FAST ) included 45 patients with SSc-related ILD who were r and omized to receive prednisolone ( 20 mg per day ) and 6 CYC infusions ( 600 mg/m monthly ) or placebo . This trial did not demonstrate significant improvement of the primary or secondary endpoints in the active treatment group versus placebo . Since with the exception of the study of Silver et al. none of the patients included in retrospective or prospect i ve studies were selected on the basis of progression of ILD . Since only a minority of SSc patients develops severe ILD , we propose that further studies evaluating CYC should focus on the subgroup of SSc patients with worsening ILD IMPORTANCE High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation ( HSCT ) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials . OBJECTIVE To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide . DESIGN , SETTING , AND PARTICIPANTS The Autologous Stem Cell Transplantation International Scleroderma ( ASTIS ) trial , a phase 3 , multicenter , r and omized ( 1:1 ) , open-label , parallel-group , clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility . From March 2001 to October 2009 , 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31 , 2013 . INTERVENTIONS HSCT vs intravenous pulse cyclophosphamide . MAIN OUTCOMES AND MEASURES The primary end point was event-free survival , defined as time from r and omization until the occurrence of death or persistent major organ failure . RESULTS A total of 156 patients were r and omly assigned to receive HSCT ( n = 79 ) or cyclophosphamide ( n = 77 ) . During a median follow-up of 5.8 years , 53 events occurred : 22 in the HSCT group ( 19 deaths and 3 irreversible organ failures ) and 31 in the control group ( 23 deaths and 8 irreversible organ failures ) . During the first year , there were more events in the HSCT group ( 13 events [ 16.5 % ] , including 8 treatment-related deaths ) than in the control group ( 8 events [ 10.4 % ] , with no treatment-related deaths ) . At 2 years , 14 events ( 17.7 % ) had occurred cumulatively in the HSCT group vs 14 events ( 18.2 % ) in the control group ; at 4 years , 15 events ( 19 % ) had occurred cumulatively in the HSCT group vs 20 events ( 26 % ) in the control group . Time-varying hazard ratios ( modeled with treatment × time interaction ) for event-free survival were 0.35 ( 95 % CI , 0.16 - 0.74 ) at 2 years and 0.34 ( 95 % CI , 0.16 - 0.74 ) at 4 years . CONCLUSIONS AND RELEVANCE Among patients with early diffuse cutaneous systemic sclerosis , HSCT was associated with increased treatment-related mortality in the first year after treatment . However , HCST conferred a significant long-term event-free survival benefit . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N54371254 To evaluate changes in vascular and musculoskeletal involvement in subjects in the Scleroderma Lung Study , a multicenter , double‐blind , r and omized , controlled trial comparing placebo treatment with oral cyclophosphamide ( CYC ) for 1 year in systemic sclerosis patients with interstitial lung disease . Subjects were then followed off the study agent for an additional 12 months BACKGROUND The Scleroderma Lung Study ( SLS ) was a 1-year , r and omized , controlled trial of oral cyclophosphamide for scleroderma-related pulmonary alveolitis . It concluded that oral cyclophosphamide slowed the decline in the forced vital capacity ( % predicted ) and had a beneficial effect on dyspnea , skin changes , and several quality of life measures of systemic sclerosis . We now report an in-depth assessment of the toxicity of cyclophosphamide during the year of therapy and the year after therapy was completed , during which time the investigators were still masked to the treatment assignment . METHODS One-year , double-blind , r and omized controlled trial of oral cyclophosphamide versus placebo with 1-year masked follow-up . Adverse events ( AEs ) were tabulated , described , and compared using descriptive statistics ( eg , mean and median ) and t , Wilcoxon rank sum , chi-squared , or Fisher 's exact tests as appropriate . RESULTS During year 1 , treatment-related overall AEs occurred more frequently in cyclophosphamide (CYC)-treated patients ( overall AEs for CYC=154 events vs placebo=60 events ; P=0.002 ) , and especially for mild to moderate leukopenia ( CYC=19 subjects vs placebo=0 subjects ; P < .0001 ) . For cancer , we followed patients beyond 2 years . There were no differences in the occurrence of cancer ( CYC=4 subjects vs placebo=2 subjects ) , serious related AEs ( CYC=8 events vs placebo=13 events ) , or deaths ( CYC=6 subjects vs placebo=6 subjects ) . CONCLUSION Over 2 years , cyclophosphamide was associated with more AEs than placebo , including overall AEs and relative leukopenia . There were no differences in other AEs , including serious AEs , cancers , or deaths |
11,151 | 28,969,342 | Conclusions Results indicate that ingestion of n-3 PUFAs does not significantly alter cognitive performance in cognitively healthy persons . | Context There has been interest in identifying whether nutrients might help optimize cognitive performance , especially for the military tasked with ensuring mission-readiness .
Objective This systematic review assesses the quality of the evidence for n-3 polyunsaturated fatty acids ( PUFAs ) across various outcomes related to cognitive function in healthy adult population s in order to develop research recommendations concerning n-3 PUFAs for mission-readiness . | Low dietary intakes of the n-3 long-chain PUFA ( LCPUFA ) EPA and DHA are thought to be associated with increased risk for a variety of adverse outcomes , including some psychiatric disorders . Evidence from observational and intervention studies for a role of n-3 LCPUFA in depression is mixed , with some support for a benefit of EPA and /or DHA in major depressive illness . The present study was a double-blind r and omised controlled trial that evaluated the effects of EPA+DHA supplementation ( 1.5 g/d ) on mood and cognitive function in mild to moderately depressed individuals . Of 218 participants who entered the trial , 190 completed the planned 12 weeks intervention . Compliance , confirmed by plasma fatty acid concentrations , was good , but there was no evidence of a difference between supplemented and placebo groups in the primary outcome - namely , the depression subscale of the Depression Anxiety and Stress Scales at 12 weeks . Mean depression score was 8.4 for the EPA+DHA group and 9.6 for the placebo group , with an adjusted difference of - 1.0 ( 95 % CI - 2.8 , 0.8 ; P = 0.27 ) . Other measures of mood , mental health and cognitive function , including Beck Depression Inventory score and attentional bias toward threat words , were similarly little affected by the intervention . In conclusion , substantially increasing EPA+DHA intake for 3 months was found not to have beneficial or harmful effects on mood in mild to moderate depression . Adding the present result to a meta- analysis of previous relevant r and omised controlled trial results confirmed an overall negligible benefit of n-3 LCPUFA supplementation for depressed mood BACKGROUND Docosahexaenoic acid ( DHA ) is important for brain function , and its status is dependent on dietary intakes . Therefore , individuals who consume diets low in omega-3 ( n-3 ) polyunsaturated fatty acids may cognitively benefit from DHA supplementation . Sex and apolipoprotein E genotype ( APOE ) affect cognition and may modulate the response to DHA supplementation . OBJECTIVES We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response . DESIGN Healthy adults ( n = 176 ; age range : 18 - 45 y ; nonsmoking and with a low intake of DHA ) completed a 6-mo r and omized , placebo-controlled , double-blind intervention in which they consumed 1.16 g DHA/d or a placebo . Cognitive performance was assessed by using a computerized cognitive test battery . For all tests , z scores were calculated and clustered into cognitive domains as follows : episodic and working memory , attention , reaction time ( RT ) of episodic and working memory , and attention and processing speed . ANCOVA was conducted with sex and APOE as independent variables . RESULTS RTs of episodic and working memory improved with DHA compared with placebo [ mean difference ( 95 % CI ) : -0.18 SD ( -0.33 , -0.03 SD ) ( P = 0.02 ) and -0.36 SD ( -0.58 , -0.14 SD ) ( P = 0.002 ) , respectively ] . Sex × treatment interactions occurred for episodic memory ( P = 0.006 ) and the RT of working memory ( P = 0.03 ) . Compared with the placebo , DHA improved episodic memory in women [ 0.28 SD ( 0.08 , 0.48 SD ) ; P = 0.006 ] and RTs of working memory in men [ -0.60 SD ( -0.95 , -0.25 SD ) ; P = 0.001 ] . APOE did not affect cognitive function , but there were some indications of APOE × sex × treatment interactions . CONCLUSIONS DHA supplementation improved memory and the RT of memory in healthy , young adults whose habitual diets were low in DHA . The response was modulated by sex . This trial was registered at the New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au/default.aspx ) as ACTRN12610000212055 While cardiovascular and mood benefits of dietary omega-3 fatty acids such as docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) are manifest , direct neurophysiological evidence of their effects on cortical activity is still limited . Hence we chose to examine the effects of two proprietary fish oil products with different EPA∶DHA ratios ( EPA-rich , high EPA∶DHA ; DHA-rich ) on mental processing speed and visual evoked brain activity . We proposed that nonlinear multifocal visual evoked potentials ( mfVEP ) would be sensitive to any alteration of the neural function induced by omega-3 fatty acid supplementation , because the higher order kernel responses directly measure the degree of recovery of the neural system as a function of time following stimulation . Twenty-two healthy participants aged 18–34 , with no known neurological or psychiatric disorder and not currently taking any nutritional supplementation , were recruited . A double-blind , crossover design was utilized , including a 30-day washout period , between two 30-day supplementation periods of the EPA-rich and DHA-rich diets ( with order of diet r and omized ) . Psychophysical choice reaction times and multi-focal nonlinear visual evoked potential ( VEP ) testing were performed at baseline ( No Diet ) , and after each supplementation period . Following the EPA-rich supplementation , for stimulation at high luminance contrast , a significant reduction in the amplitude of the first slice of the second order VEP kernel response , previously related to activation in the magnocellular pathway , was observed . The correlations between the amplitude changes of short latency second and first order components were significantly different for the two supplementations . Significantly faster choice reaction times were observed psychophysically ( compared with baseline performance ) under the EPA-rich ( but not DHA-rich ) supplementation , while simple reaction times were not affected . The reduced nonlinearities observed under the EPA-rich diet suggest a mechanism involving more efficient neural recovery of magnocellular-like visual responses following cortical activation Abstract Sleep deprivation can impair alertness and cognitive and motor performance . We hypothesized that the amino acid tyrosine might reduce deleterious effects of sleep deprivation . Seventy-six healthy males , age 18 - 35 years , participated in a four-day protocol that included a habituation night , a baseline night , a 40.5 h period without sleep , and a recovery night . Tyrosine 150 mg/kg , caffeine 300 mg/70 kg , phentermine 37.5 mg , d-amphetamine 20 mg and placebo were administered in a double-blind , r and omized fashion to compare their effects on the time it took to fall asleep , on endocrine responses during sleep deprivation , and on sleep quantity , quality and architecture as measured by polysomnography during recovery sleep . When given after 36 h without sleep , tyrosine had no significant effect on any parameter of sleep . d-amphetamine produced marked decrease in sleep drive but caused deleterious effects on many aspects of recovery sleep . Still , d-amphetamine was associated with increased alertness on the first recovery day . Phentermine and caffeine both decreased sleep drive during sleep deprivation , but phentermine impaired rapid-eye-movement ( REM ) recovery sleep . Tyrosine ( when compared to placebo ) had no effect on any sleep related measure , but it did stimulate prolactin release Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders , particularly for depression . Association studies show a relationship between omega-3 intake and depression risk . Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms , but not on normal mood states . Few studies have investigated effects on cognition . The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals . Seventy-one participants were r and omized to receive either omega-3 or placebo for four weeks in a r and omized double-blind design . Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension . Some of the effects were confounded by learning effects . No significant effects were observed on memory , attention , cognitive reactivity and depressive symptoms . While inconclusive , the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants IMPORTANCE Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease . OBJECTIVE To test the effects of oral supplementation with nutrients on cognitive function . DESIGN , SETTING , AND PARTICIPANTS In a double-masked r and omized clinical trial ( the Age-Related Eye Disease Study 2 [ AREDS2 ] ) , retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration ( AMD ) from October 2006 to December 2012 . In addition to annual eye examinations , several vali date d cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study . INTERVENTIONS Long-chain polyunsaturated fatty acids ( LCPUFAs ) ( 1 g ) and /or lutein ( 10 mg)/zeaxanthin ( 2 mg ) vs placebo were tested in a factorial design . All participants were also given varying combinations of vitamins C , E , beta carotene , and zinc . MAIN OUTCOMES AND MEASURES The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline . The analyses , which were adjusted for baseline age , sex , race , history of hypertension , education , cognitive score , and depression score , evaluated the differences in the composite score between the treated vs untreated groups . The composite score provided an overall score for the battery , ranging from -22 to 17 , with higher scores representing better function . RESULTS A total of 89 % ( 3741/4203 ) of AREDS2 participants consented to the ancillary cognitive function study and 93.6 % ( 3501/3741 ) underwent cognitive function testing . The mean ( SD ) age of the participants was 72.7 ( 7.7 ) years and 57.5 % were women . There were no statistically significant differences in change of scores for participants r and omized to receive supplements vs those who were not . The yearly change in the composite cognitive function score was -0.19 ( 99 % CI , -0.25 to -0.13 ) for participants r and omized to receive LCPUFAs vs -0.18 ( 99 % CI , -0.24 to -0.12 ) for those r and omized to no LCPUFAs ( difference in yearly change , -0.03 [ 99 % CI , -0.20 to 0.13 ] ; P = .63 ) . Similarly , the yearly change in the composite cognitive function score was -0.18 ( 99 % CI , -0.24 to -0.11 ) for participants r and omized to receive lutein/zeaxanthin vs -0.19 ( 99 % CI , -0.25 to -0.13 ) for those r and omized to not receive lutein/zeaxanthin ( difference in yearly change , 0.03 [ 99 % CI , -0.14 to 0.19 ] ; P = .66 ) . Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant . CONCLUSIONS AND RELEVANCE Among older persons with AMD , oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00345176 Abstract Omega-3 polyunsaturated fatty acid ( n-3 PUFA ) supplementation may be beneficial in the treatment of several psychiatric disorders , including depression . A small number of studies have suggested that there may also be cognitive and mood effects in healthy sample s. The purpose of the present study was to investigate the effects of n-3 PUFA on depression-relevant cognitive functioning in healthy individuals . Fifty-four healthy university students were r and omized to receive either n-3 PUFA supplements or placebo for 4 weeks in a double-blind design . The test battery included measures of cognitive reactivity , attention , response inhibition , facial emotion recognition , memory and risky decision-making . Results showed few effects of n-3 PUFAs on cognition and mood states . The n-3 PUFA group made fewer risk-averse decisions than the placebo group . This difference appeared only in non-normative trials of the decision-making test , and was not accompanied by increased impulsiveness . N-3 PUFAs improved scores on the control/perfectionism scale of the cognitive reactivity measure . No effects were found on the other cognitive tasks and no consistent effects on mood were observed . The present findings indicate that n-3 PUFA supplementation may have a selective effect on risky decision making in healthy volunteers , which is unrelated to impulsiveness The omega-3 fatty acid docosahexaenoic acid ( DHA ) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging . A triple-blind placebo-controlled r and omized repeated- measures trial was conducted with 74 healthy participants , aged 45 - 77 years . Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA ( ® ) ( Clover Corp. , Sydney , NSW , Australia : 1000 mg of tuna oil ; comprising 252 mg DHA , 60 mg EPA and 10 mg vitamin E ) or placebo ( 1000 mg soybean oil ) . Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group , as well as significantly lower total ω-6 levels . However , no significant effects of DHA supplementation on cognitive functioning were found . For participants with corrected vision , the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group ( F(1,22 ) = 7.651 ; p = 0.011 ; partial η(2 ) = 0.258 ) BACKGROUND Biochemical and behavioral evidence has suggested that the ratio of n-6 ( omega-6 ) to n-3 ( omega-3 ) could be an important predictor of executive function abilities in children . OBJECTIVE We determined the relation between the ratio of n-6 to n-3 and cognitive function in children . We hypothesized that children with lower ratios of n-6 to n-3 fatty acids would perform better on tests of planning and working memory . DESIGN Seventy 7- to 9-y-old children completed three 24-h diet recalls and a subset of the Cambridge Neuropsychological Test Assessment Battery . Parents provided information on their demographics and children 's diet histories . RESULTS Mean n-3 and mean n-6 intakes were related to the mean time spent on each action taken in the planning problem . The ratio of n-6 to n-3 significantly predicted performance on the working memory and planning problems . There was a significant interaction between the ratio and fatty acid intake ; when children had high ratios , a higher intake of n-3 fatty acids predicted a better performance on the planning task than when children had lower n-3 intakes . When children had low ratios , a lower intake of n-3 and lower intake of n-6 predicted better performance than when intakes were higher . CONCLUSIONS The relation between cognitive abilities and the ratio of n-6 to n-3 may be mediated by an enzymatic affinity for n-3 fatty acids . The ratio of n-6 to n-3 should be considered an important factor in the study of fatty acids and cognitive development . This trial was registered at clinical trials.gov as NCT01823419 BACKGROUND Increased consumption of n-3 ( omega-3 ) long-chain polyunsaturated fatty acids ( LC PUFAs ) , especially eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , may maintain cognitive function in later life . OBJECTIVE We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people . DESIGN At total of 867 cognitively healthy adults , aged 70 - 79 y , from 20 general practice s in Engl and and Wales were r and omly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo . Treatment-allocation codes were obtained from a central computerized r and omization service . Trained research nurses administered a battery of cognitive tests , including the primary outcome , the California Verbal Learning Test ( CVLT ) , at baseline and 24 mo . Intention-to-treat analysis of covariance , with adjustment for baseline cognitive scores , age , sex , and age at leaving full-time education , included 748 ( 86 % ) individuals who completed the study . RESULTS The mean age of participants was 75 y ; 55 % of the participants were men . Withdrawals and deaths were similar in active ( n = 49 and n = 9 , respectively ) and placebo ( n = 53 and n = 8 , respectively ) arms . Mean ( + /-SD ) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo ( 49.9 + /- 2.7 mg EPA/L in the active arm compared with 39.1 + /- 3.1 mg EPA/L in the placebo arm ; 95.6 + /- 3.1 mg DHA/L in the active arm compared with 70.7 + /- 2.9 mg DHA/L in the placebo arm ) . There was no change in cognitive function scores over 24 mo , and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome . CONCLUSIONS Cognitive function did not decline in either study arm over 24 mo . The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study . The Older People And n-3 Long-chain polyunsaturated fatty acids ( OPAL ) Study was registered at www.controlled-trials.com as IS RCT N 72331636 Omega-3 fatty acid ( n-3 PUFA ) intake is associated with improved mood and cognition , but r and omized controlled trials addressing the causal nature of such relationships are less clear , especially in healthy , young adults . Stress is one potential mechanism by which n-3 PUFAs may influence mood . Thus the present aim is to evaluate the influence of n-3 PUFA supplementation on stress-induced changes to mood , cognition , and physiological stress markers in healthy , young adults . Using a double-blind , placebo-controlled design , 72 young adults were r and omized to receive 2800mg/day fish oil ( n=36 , 23 females ) or olive oil control ( n=36 , 22 females ) for 35days . Subjects completed measures of mood and cognition before supplementation , and two times after supplementation : following an acute stressor or non-stressful control task . The stress induction was effective in that the stressor impaired mood , including augmenting feelings of tension , anger , confusion and anxiety , reduced accuracy on a cognitive task measuring attentional control and the ability to regulate emotion , and increased salivary cortisol and pro-inflammatory cytokine interleukin-1β ( IL-1β ) . Rated anger and confusion increased with stress in the olive oil group , but remained stable in the fish oil group . However , fish oil had no further effects on mood , cognitive function , cortisol , or IL-1β . Fish oil exerted few effects in stressful and non-stressful situations , consistent with findings showing little influence of n-3 PUFA supplementation on mood and cognition in young , healthy individuals . Potential target population s who would more likely benefit from increased n-3 PUFA intake are discussed Background : High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline . However , results from epidemiologic studies are inconclusive , and results from r and omized trials in elderly subjects without dementia are lacking . Objective : To investigate the effect of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) supplementation on cognitive performance . Methods : Double-blind , placebo-controlled trial involving 302 cognitively healthy ( Mini-Mental State Examination score > 21 ) individuals aged 65 years or older . Participants were r and omly assigned to 1,800 mg/d EPA – DHA , 400 mg/d EPA – DHA , or placebo capsules for 26 weeks . Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention , sensorimotor speed , memory , and executive function . Results : The mean age of the participants was 70 years , and 55 % were male . Plasma concentrations of EPA – DHA increased by 238 % in the high-dose and 51 % in the low-dose fish oil group compared with placebo , reflecting excellent compliance . Baseline scores on the cognitive tests were comparable in the three groups . Overall , there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo . Conclusions : In this r and omized , double-blind , placebo-controlled trial , we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance Abstract Introduction : Low dietary intake of docosahexaenoic acid ( DHA ) and /or foods rich in lutein may be associated with increased risk of cognitive decline in the elderly . Subjects and methods : The cognitive benefit of DHA and lutein in unimpaired elder women was explored in the context of a 4-month , double-blind , intervention trial of DHA and lutein supplementation for eye health . Forty-nine women ( aged 60–80 years ) were r and omized to receive DHA ( 800 mg/day ; n = 14 ) , lutein ( 12 mg/day ; n = 11 ) , a combination of DHA and lutein ( n = 14 ) or placebo ( n = 10 ) . Subjects underwent cognitive tests measuring verbal fluency , memory , processing speed and accuracy , and self-reports of mood at r and omization and upon completion of the trial . Results : Following supplementation , verbal fluency scores improved significantly in the DHA , lutein , and combined treatment groups ( P < 0.03 ) . Memory scores and rate of learning improved significantly in the combined treatment group ( P < 0.03 ) , who also displayed a trend toward more efficient learning ( P = 0.07 ) . Measures of mental processing speed , accuracy and mood were not affected by supplementation . Conclusions : These exploratory findings suggest that DHA and lutein supplementation may have cognitive benefit for older adults |
11,152 | 24,379,677 | Simvastatin has an extensive first-pass effect in the intestinal wall , whereas atorvastatin has a smaller intestinal first-pass effect .
The interaction with simvastatin seems mainly driven by CYP3A4 inhibition at the intestinal level , whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition .
The interaction of CYP3A4 inhibitor with simvastatin has been more pronounced compared with atorvastatin .
From the current data , atorvastatin seems to be a safer CYP3A4-statin for comedication with DHP-CCB .
There is no convincing evidence that amlodipine is an unusual DHP-CCB , either as a precipitant drug or as an object drug , from the perspective of CYP3A4-mediated drug metabolism .
Amlodipine may have interactions with CYP3A5 in addition to CYP3A4 , which may explain its particular characteristics in comparison with other DHP-CCBs . | BACKGROUND Coadministration of 1,4-dihydropyridine calcium channel blockers ( DHP-CCBs ) with statins ( or 3-hydroxy-3-methylglutaryl-coenzyme A [ HMG-CoA ] reductase inhibitors ) is common for patients with hypercholesterolemia and hypertension .
To reduce the risk of myopathy , in 2011 , the US Food and Drug Administration ( FDA ) Drug Safety Communication set a new dose limitation for simvastatin , for patients taking simvastatin concomitantly with amlodipine .
However , there is no such dose limitation for atorvastatin for patients receiving amlodipine .
The combination pill formulation of amlodipine/atorvastatin is available on the market .
There been no systematic review of the pharmacokinetic drug-drug interaction ( DDI ) profile of DHP-CCBs with statins , the underlying mechanisms for DDIs of different degree , or the corresponding management of clinical risk . | 3-Hydroxy-3-methylglutaryl-coenzyme A ( HMG-CoA ) reductase inhibitors are often prescribed in association with antihypertensive agents , including calcium antagonists . Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by the cytochrome P450 ( CYP ) 3A4 . The calcium antagonist amlodipine is also metabolized by CYP3A4 . The purpose of this study was to investigate drug interactions between amlodipine and simvastatin . Eight patients with hypercholesterolemia and hypertension were enrolled . They were given 4 weeks of oral simvastatin ( 5 mg/day ) , followed by 4 weeks of oral amlodipine ( 5 mg/day ) co-administered with simvastatin ( 5 mg/day ) . Combined treatment with simvastatin and amlodipine increased the peak concentration ( Cmax ) of HMG-CoA reductase inhibitors from 9.6 ±3.7 ng/ml to 13.7±4.7 ng/ml ( p<0.05 ) and the area under the concentration-time curve ( AUC ) from 34.3±16.5 ng h/ml to 43.9±16.6 ng h/ml ( p<0.05 ) without affecting the cholesterol-lowering effect of simvastatin . This study is the first to determine prospect ively the pharmacokinetic and pharmacodynamic interaction between amlodipine and simvastatin Purpose To characterise further the previously observed cytochrome P450 3A4 ( CYP3A4 ) interaction of the dual orexin receptor antagonist almorexant . Methods Pharmacokinetic interactions were investigated ( n = 14 healthy male subjects in two treatment groups ) between almorexant at steady-state when administered either concomitantly or 2 h after administration of single doses of simvastatin ( 40 mg ) or atorvastatin ( 40 mg ) . Results Almorexant dose-dependently increased simvastatin exposure ( AUC0–∞ ) when administered concomitantly [ geometric mean ratios ( 90 % CI ) : 2.5 ( 2.1 , 2.9 ) ( 100 mg ) , 3.9 ( 3.3 , 4.6 ) ( 200 mg ) ] , but not Cmax [ 3.7 ( 3.0 , 4.5 ) for both doses ] . Time-separated administration result ed in relevant reductions of the interaction [ AUC0–∞ : 1.4 ( 1.2 , 1.7 ) ( 100 mg ) , 1.7 ( 1.5 , 2.0 ) ( 200 mg ) ; Cmax : 1.5 ( 1.3 , 1.9 ) ( 100 mg ) , 1.9 ( 1.6 , 2.4 ) ( 200 mg ) ] . Similar results were obtained for hydroxyacid simvastatin . Independent of almorexant dose and relative time of administration , AUC0–∞ and Cmax of atorvastatin increased ( ratios ranged from 1.1 to 1.5 ) . AUC0–∞ and Cmax of o-hydroxy atorvastatin decreased dose-independently [ AUC0–∞ : 0.8 ( 0.8 , 0.9 ) ( 100 mg ) , 0.6 ( 0.5 , 0.6 ) ( 200 mg ) ; Cmax : 0.3 ( 0.3 , 0.4 ) ( 100 mg ) , 0.2 ( 0.2 , 0.3 ) ( 200 mg ) ] when atorvastatin was concomitantly administered . Cmax of o-hydroxy atorvastatin slightly decreased ( 0.8 for both doses ) following time-separated administration ; AUC0–∞ was unchanged . Conclusions Whereas almorexant increased simvastatin exposure dose- and relative time of administration-dependently , atorvastatin exposure increased to a smaller extent and irrespective of dose and time . This suggests that the observed interaction of almorexant with simvastatin is mainly caused by intestinal CYP3A4 inhibition , whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition Three-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors ( statins ) are first-line treatments for hypercholesterolemia . Although exceedingly well tolerated , treatment with statins incurs a small risk of myopathy or potentially fatal rhabdomyolysis , particularly when coadministered with medications that increase their systemic exposure . Studies compared the multiple-dose pharmacokinetic interaction profiles of pravastatin , simvastatin , and atorvastatin when coadministered with 4 inhibitors of cytochrome P450 - 3A4 isoenzymes in healthy subjects . Compared with pravastatin alone , coadministration of verapamil , mibefradil , or itraconazole with pravastatin was associated with no significant changes in pravastatin pharmacokinetics . However , concomitant verapamil increased the simvastatin area under the concentration : time curve ( AUC ) approximately fourfold , the maximum serum concentration ( C(max ) ) fivefold , and the active metabolite simvastatin acid AUC and C(max ) approximately four- and threefold , respectively ( all comparisons p < 0.001 ) . Similar ( greater than fourfold ) important increases in these parameters and a > 60 % increase in the serum half-life ( p = 0.03 ) of atorvastatin were observed when coadministered with mibefradil . The half-life of atorvastatin also increased by approximately 60 % ( p = 0.052 ) when coadministered with itraconazole , which elicited a 2.4-fold increase in the C(max ) of atorvastatin and a 47 % increase in the AUC ( p < 0.001 for C(max ) and AUC ) . Clarithromycin significantly ( p < 0.001 ) increased the AUC ( and C(max ) ) of all 3 statins , most markedly simvastatin ( approximately 10-fold increase in AUC ) and simvastatin acid ( 12-fold ) , followed by atorvastatin ( greater than fourfold ) and then pravastatin ( almost twofold ) . Pravastatin has a neutral drug interaction profile relative to cytochrome P450 - 3A4 inhibitors , but these substrates markedly increase systemic exposure to simvastatin and atorvastatin The objective of this study was to evaluate the effect of the CYP3A5 * 3 allele on the pharmacokinetics of tacrolimus and amlodipine , and drug-drug interactions between them in healthy subjects . Pharmacokinetic drug interactions between tacrolimus and amlodipine were evaluated in a r and omized , 3-period , 6-sequence crossover study in healthy Chinese volunteers according to CYP3A5 genotype . A single-dose and multiple-dose study were design ed . A 96-h pharmacokinetic study followed either tacrolimus or amlodipine dose , and the washout periods between the study phases were 14 days . In the single-dose study , apparent oral clearance ( CL/F ) of tacrolimus ( 5 mg ) in CYP3A5 expressers was 3.8-fold ( p = 0.008 ) higher than that in CYP3A5 non-expressers . Amlodipine decreased mean tacrolimus CL/F in CYP3A5 expressers by 2.2-fold ( p = 0.005 ) , while it had no effect on that in CYP3A5 non-expressers . The CL/F of amlodipine in CYP3A5 non-expressers was 2.0-fold ( p = 0.001 ) higher than that in CYP3A5 expressers . Tacrolimus increased mean amlodipine CL/F in CYP3A5 expressers by 1.4-fold ( p = 0.016 ) while it had no effect on that in CYP3A5 non-expressers . Tacrolimus slightly reduced the AUC₀-∞ of amlodipine in both CYP3A5 expressers and non-expressers . Dose adjustment of tacrolimus should be considered according to CYP3A5 * 3 genetic polymorphism when tacrolimus is coadministered with amlodipine AIMS Lacidipine , a long acting 2 , 4-dihydropyridine calcium channel antagonist is frequently administered with cholesterol lowering agents , particularly in elderly population s. The effects of lacidipine on the pharmacokinetics of simvastatin were investigated , since they share the CYP3A4 pathway for metabolism . METHODS The study was an open , r and omised , two-way crossover design , with at least 7 days washout . Eighteen healthy subjects received simvastatin , 40 mg once daily , alone and together with lacidipine , 4 mg once daily , for 8 days . The pharmacokinetics of simvastatin were studied on the eighth day . Analysis was made of total simvastatin acid concentrations ( naive simvastatin acid plus that derived from alkaline hydrolysis of the lactone ) . RESULTS Lacidipine increased the maximum concentration of simvastatin ( Cmax ) by approximately 70 % ( P=0.016 ) and the area under the plasma concentration-time curve AUC(0,24 h ) by approximately 35 % ( P=0.001 ) . The mean Cmax and AUC(0,24 h ) of simvastatin ( 95 % confidence interval ) when given alone were 8.76 ( 6.72 - 11.41 ) ng ml(-1 ) and 60.36 ( 47.15 - 77.28 ) ng ml(-1 ) h. During treatment with lacidipine they were , respectively , 14.89 ( 10.77 - 20.58 ) ng ml(-1 ) and 80.96 ( 64.62 - 101.44 ) ng ml(-1 ) h. No significant differences were observed in either time to peak concentration ( tmax was 1.0 h for simvastatin alone and 1.5 h for the combination ) or in the half-life ( t1/2,z was 8.5 h in both cases ) . The combination was safe and well tolerated . CONCLUSIONS The observed increased exposure to simvastatin 40 mg following coadministration of lacidipine is unlikely to be of clinical relevance OBJECTIVES To explore if non-concurrent amlodipine dosing results in less drug interaction , the pharmacokinetic profiles , safety and efficacy endpoints were assessed following repeated doses of simvastatin , co-administered concurrently or non-concurrently with amlodipine in patients with coexisting hypertension and hyperlipidemia . METHODS Seventeen patients r and omly received daily doses of 20 mg simvastatin and 5 mg amlodipine for 6 weeks , either with both drugs at 7:00 PM ( concurrent ) or with simvastatin at 7:00 PM followed by amlodipine at 11:00 PM ( non-concurrent ) . The maximum plasma concentration ( Cmax ) and the area under the concentration-time curve up to the last quantifiable concentration ( AUClast ) were estimated at steady state . Lipid profiles and blood pressure values were also compared between the concurrent and non-concurrent groups . RESULTS The Cmax and AUClast and of simvastatin acid in the non-concurrent amlodipine dosing group were 63.2 % and 66.0 % , respectively , of the values obtained in the concurrent group ( 1.2 + /- 1.0 vs. 1.9 + /- 0.9 ng/ml and 10.3 + /- 8.3 vs. 15.6 + /- 7.5 h ng/ml , respectively , mean + /- st and ard deviation ) . Changes from baseline in lipid profile and blood pressure were comparable between the groups . CONCLUSIONS Non-concurrent dosing may be a useful and safe therapeutic option for patients who require two or more drugs administered concomitantly , but who are likely to develop unwanted drug interactions A r and omized cross-over pharmacokinetic study of rosuvastatin calcium ( single dose : 5 mg , 10 mg and 20 mg ; multiple doses : 10 mg once daily for 7 days ) was conducted in 12 healthy Chinese volunteers . Plasma concentrations of rosuvastatin were determined by an LC-ESI-MS-MS method . Single-nucleotide polymorphisms ( SNPs ) in ABCB1 , ABCG2 , SLCOB1 , CYP2C9 and CYP3A5 were determined by TaqMan ( MGB ) genotyping assay . An impact of the aforementioned SNPs on steady state pharmacokinetic parameters [ average steady state concentration ( Cav , ss ) and area under the plasma concentration versus time curve during the dosing interval at steady state ( AUCss ) ] , dose-normalized ( based on 5 mg ) pharmacokinetic parameters of single-dose rosuvastatin were further analyzed . Rosuvastatin exhibited linear pharmacokinetics and great inter-subject variability . Cav , ss , AUCss and dose-normalized peak plasma concentration ( Cmax ) and AUC(0-infinity ) of single-dose rosuvastatin were significantly related with ABCB1 C1236 T , G2677T/A and C3435 T polymorphisms and ABCB1 haplotypes . Compared to homozygous wild type and heterozygous mutation gene carriers , subjects carrying the variant ABCB1 1236TT , 2677 non-G or 3435TT genotype had higher Cav , ss , AUCss , Cmax and AUC(0-infinity ) ( p < 0.05 ) . ABCB1 haplotype ( 1236TT-2677TT-3435TT ) had significant influence on dose-normalized pharmacokinetics of single-dose rosuvastatin . ABCB1 haplotype ( 1236TT-2677TT-3435TT ) carriers ( n = 12 ) had obvious higher Cmax ( 11.16 + /- 3.10 microg x L(-1 ) vs 8.35 + /- 3.31 microg x L(-1 ) , p < 0.05 ) and AUC(0-infinity ) ( 86.61 + /- 24.32 microg x h x L(-1 ) vs 62.60 + /- 26.19 microg x h x L(-1 ) , p < 0.05 ) compared to non-1236TT-2677TT-3435TT carriers ( n = 24 ) . ABCG2 c.421C > A had a significant impact on rosuvastatin pharmacokinetics . Homozygotes ( AA ) carriers had obvious higher Cmax ( 12.20 + /- 4.09 microg x L(-1 ) vs 8.70 + /- 3.09 microg x L(-1 ) , p < 0.05 ) and AUC(0-infinity ) ( 98.74 + /- 25.36 microg x h x L(-1 ) vs 64.97 + /- 24.90 microg x h x L(-1 ) , p < 0.05 ) values compared to heterozygotes ( CA ) and homozygotes ( CC ) carriers . There were no significant effects on single-dose and steady-state pharmacokinetics of rosuvastatin by CYP2C9 * 3 ( 1075A > C ) , CYP3A5 * 3 g.6986A > G , ABCG2 c.34 G > A , SLCO1B1 c.521 T > C , c.388 A > G , g.11187 G > A , c.571 T > C and c.597 C > T. In addition , no difference in rosuvastatin pharmacokinetics was observed among subjects of different genders . We conclude that ABCB1 C1236 T , G2677T/A and C3435 T polymorphism , ABCB1 haplotypes and ABCG2 c.421C > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics in healthy Chinese volunteers , and potentially affect the efficacy and toxicity of statin therapy Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient . Fluvastatin ( FV ) , used to reduce cholesterol levels , and lercanidipine ( LER ) , used to control blood pressure , are marketed as racemic mixtures . Therapeutic activities are 30-fold higher for (+)-3R , 5S-FV and 100- to 200-fold higher for S-LER compared with their respective antipodes . The present study describes the enantioselective pharmacokinetic interaction between LER and FV in healthy volunteers . A crossover r and omized study was conducted in 3 phases on 8 volunteers treated with a single oral racemic dose of LER ( 20 mg ) or FV ( 40 mg ) or LER plus FV . Serial blood sample s were collected from 0 to 24 hours . Plasma concentrations of the LER and FV enantiomers were determined by liquid chromatography/t and em mass spectrometry , and pharmacokinetic parameters were evaluated using the WinNonlin software . The Wilcoxon and Mann-Whitney tests ( P < .05 ) were used to analyze enantiomer ratios and the pharmacokinetic drug interaction . Data are expressed as medians . In monotherapy , the kinetic disposition of both FV and LER was enantioselective . AUC values were significantly higher for (-)-3S,5R-FV than for (+)-3R,5S-FV ( 358.20 vs 279.68 ng.h/mL ) and for S-LER compared with R-LER ( 13.90 vs 11.88 ng.h/mL ) . The pharmacokinetic parameters of FV were not enantioselective when combined with LER ( AUC : (-)-3S,5R-FV : 325.21 ; (+)-3R,5S-FV : 316.44 ng.h/mL ) . There was a significant reduction in S-LER ( 8.06 vs 13.90 ng.h/mL ) and R-LER ( 6.76 vs 11.88 ng.h/mL ) AUC values when FV was coadministered . In conclusion , the interaction between FV-LER might be clinical ly relevant because AUC values of (+)-3R,5S-FV were increased when LER was coadministered , and AUC values of the 2 LER enantiomers were reduced when FV was coadministered The bioequivalence of combination tablets containing amlodipine besylate/atorvastatin calcium with coadministered matching doses of amlodipine besylate and atorvastatin calcium tablets was investigated in r and omized , 2-way crossover studies in healthy volunteers ( N = 126 ) . Subjects received a single dose of the amlodipine/atorvastatin tablet or coadministered matching doses of amlodipine and atorvastatin at the highest ( 10/80 mg ; n = 62 ) and lowest ( 5/10 mg ; n = 64 ) dose strengths . Atorvastatin geometric mean ratios for maximum plasma concentration ( C(max ) ) and area under the plasma concentration-time curve ( AUC ) for the highest and lowest dose strengths were 94.1 and 98.8 , and 104.5 and 103.8 , respectively . Amlodipine geometric mean ratios for C(max ) and AUC for the highest and lowest dose strengths were 100.8 and 103.4 , and 100 and 102.7 , respectively . The 90 % confidence intervals for all comparisons were within 80 % to 125 % , demonstrating bioequivalence for amlodipine and atorvastatin at both dose strengths . Use of amlodipine/atorvastatin combination tablets may provide a more integrated approach to treatment of cardiovascular risk A pharmacokinetics study was conducted in 12 Chinese volunteers following a single dose of 1 mg , 2 mg and 4 mg of pitavastatin calcium in an open-label , r and omized , three-period crossover design . Plasma concentrations of pitavastatin acid and pitavastatin lactone were determined by a HPLC method . Single-nucleotide polymorphisms ( SNPs ) in ABCB1 , ABCG2 , SLCO1B1 , CYP2C9 and CYP3A5 were determined by TaqMan ( MGB ) genotyping assay . An analysis was performed on the relationship between the aforementioned SNPs and dose-normalized ( based on 1 mg ) area under the plasma concentration-time curve extrapolated to infinity [ AUC(0-infinity ) ] and peak plasma concentration ( Cmax ) values of the acid and lactone forms of pitavastatin . Pitavastatin exhibited linear pharmacokinetics and great inter-subject variability . Compared to CYP2C9 * 1/*1 carriers , CYP2C9 * 1/*3 carriers had higher AUC(0-infinity ) and Cmax of pitavastatin acid and AUC(0-infinity ) of pitavastatin lactone ( P<0.05 ) . With respect to ABCB1 G2677T/A , non-G carriers had higher Cmax and AUC(0-infinity ) of pitavastatin acid , and Cmax of pitavastatin lactone compared to GT , GA or GG genotype carriers ( P<0.05 ) . Gene-dose effects of SLCO1B1 c.521 T > C and g.11187 G > A on pharmacokinetics of the acid and lactone forms were observed . Compared to non-SLCO1B1 * 17 carriers , SLCO1B1 * 17 carriers had higher Cmax and AUC(0-infinity ) of the acid and lactone forms ( P<0.05 ) . Significant sex difference was observed for pharmacokinetics of the lactone . Female SLCO1B1 521TT subjects had higher Cmax and AUC(0-infinity ) of pitavastatin lactone compared to male 521TT subjects , however , such gender difference disappeared in 521 TC and 521CC subjects . Pitavastatin pharmacokinetics was not significantly affected by ABCB1 C1236 T , ABCB1C3435 T , CYP3A5 * 3 , ABCG2 c.34 G > A , c.421C > A , SLCO1B1 c.388A > G , c.571T > C and c.597C > T. We conclude that CYP2C9 * 3 , ABCB1 G2677T/A , SLCO1B1 c.521T > C , SLCO1B1 g.11187 G > A , SLCO1B1 * 17 and gender contribute to inter-subject variability in pitavastatin pharmacokinetics . Personalized medicine should be necessary for hypercholesterolaemic patients receiving pitavastatin |
11,153 | 21,135,337 | No intervention improved child weight status .
Limited evidence suggests that interventions may improve dietary intake and parental attitudes and knowledge about nutrition for children in this age group . | OBJECTIVE To assess the evidence for interventions design ed to prevent or reduce overweight and obesity in children younger than 2 years . | OBJECTIVE . The goal was to examine the associations of weight-for-length at birth and at 6 months with obesity at 3 years of age . METHODS . We studied 559 children in Project Viva , an ongoing , prospect i ve , cohort study of pregnant women and their children . We measured length and weight at birth , 6 months , and 3 years . Our main exposures were weight-for-length z score at birth adjusted for gestational age and weight-for-length z score at 6 months adjusted for weight-for-length z score at birth . We used multivariate regression analyses to predict the independent effects of birth weight-for-length z score and , separately , 6-month weight-for-length z score on BMI z score , the sum of subscapular and triceps skinfold thicknesses , and obesity ( BMI for age and gender of ≥95th percentile ) at age 3 . RESULTS . Mean weights at birth , 6 months , and 3 years were 3.55 , 8.15 , and 15.67 kg , respectively . Corresponding lengths were 49.9 , 66.9 , and 97.4 cm . At 3 years , 48 children ( 9 % ) were obese . After adjustment for confounding variables and birth weight-for-length z score , each increment in 6-month weight-for-length z score was associated with higher BMI z scores , higher sums of subscapular and triceps skinfold thicknesses , and increased odds of obesity at age 3 . The predicted obesity prevalence among children in the highest quartiles of both birth and 6-month weight-for-length z scores was 40 % , compared with 1 % for children in the lowest quartiles of both . Whereas birth weight-for-length z scores were associated with higher BMI z scores , the magnitude of effect was smaller than that of weight-for-length z scores at 6 months . CONCLUSIONS . More-rapid increases in weight for length in the first 6 months of life were associated with sharply increased risk of obesity at 3 years of age . Changes in weight status in infancy may influence risk of later obesity more than weight status at birth Background Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours ( poor diet , low physical activity and high sedentary behaviour ) from their inception . These factors include the rapidly increasing prevalence of fatness throughout childhood , the instigation of obesity-promoting behaviours in infancy , and the tracking of these behaviours from childhood through to adolescence and adulthood . The Infant Feeding Activity and Nutrition Trial ( INFANT ) aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents . The intervention , conducted with parents over the infant 's first 18 months of life , will use existing social networks ( first-time parent 's groups ) and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours , and reduced sedentary behaviours in infancy . Methods / Design This cluster-r and omised controlled trial , with first-time parent groups as the unit of r and omisation , will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents ' group at Maternal and Child Health Centres . Using a two-stage sampling process , local government areas in Victoria , Australia will be r and omly selected at the first stage . At the second stage , a proportional sample of first-time parent groups within selected local government areas will be r and omly selected and invited to participate . Informed consent will be obtained and groups will then be r and omly allocated to the intervention or control group . Discussion The early years hold promise as a time in which obesity prevention may be most effective . To our knowledge this will be the first r and omised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups promotes healthy eating , physical activity and reduced sedentary behaviours . If proven to be effective , INFANT may protect children from the development of obesity and its associated social and economic costs . Trial registration Current Controlled Trials IS RCT BACKGROUND : The majority of infants in the United States are in nonparental child care , yet little is known about the effect of child care on development of obesity . OBJECTIVE : To examine the relationship between child care attendance from birth to 6 months and adiposity at 1 and 3 years of age . METHODS : We studied 1138 children from a prospect i ve cohort of pregnant women and their offspring . The main exposure was time in child care from birth to 6 months of age , overall and by type of care : ( 1 ) child care center ; ( 2 ) someone else 's home ; and ( 3 ) child 's own home by nonparent . The main outcomes were weight-for-length ( WFL ) z score at 1 year and BMI z score at 3 years of age . RESULTS : A total of 649 ( 57 % ) infants attended child care ; 17 % were cared for in a center , 27 % in someone else 's home , and 21 % in their own home by a nonparent . After adjustment for confounders , overall time in child care was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age but not skinfold thicknesses . Center and own home care were not associated with the outcomes , but care in someone else 's home was associated with an increase in both the 1- and 3-year outcomes . CONCLUSION : Child care in the first 6 months of life , especially in someone else 's home , was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age BACKGROUND Introducing nutritional and lifestyle principles to children in late infancy may permanently improve their adherence to a low-saturated fat , low-cholesterol diet , thus reducing of coronary risk factors , but worries about possible effects on growth and development have hampered such an approach . OBJECTIVE The Special Turku Coronary Risk Factor Intervention Project for Babies ( STRIP ) aim ed to decrease exposure to known environmental atherosclerosis risk factors in children 7 - 36 mo of age . DESIGN Repeated , individualized counseling aim ed at promoting a fat intake of 30 % of energy and a 1:1:1 ratio of saturated to monounsaturated to polyunsaturated fat intake was provided ( n = 540 intervention children ; 284 boys ) . Nutrition was discussed superficially with the families of the control children ( n = 522 ; 266 boys ) and food intake was recorded at 3 - 6-mo intervals by use of 3 - 4-d food diaries . Serum lipids were measured at 6 - 12-mo intervals and growth was monitored regularly . RESULTS Fat intake of the intervention ( control ) children provided 29.5 % ( 29.4 % ) of energy at the age of 8 mo , 26.6 % ( 28.5 % ) of energy at 13 mo , 30.5 % ( 33.5 % ) of energy at 24 mo , and 31 . 5 % ( 33.5 % ) of energy at 36 mo . The intervention children consistently consumed less saturated fat than did the control children ( P : < 0.0001 ) . Recommended intakes of other nutrients ( except vitamin D and occasionally iron ) were reached irrespective of the amount and type of dietary fat . Serum cholesterol , non-HDL cholesterol , and HDL-cholesterol concentrations were 3 - 6 % lower in the intervention children than in the control children . The intervention had no effect on height , weight , or head circumference gain . Fat intake did not predict children 's growth patterns . CONCLUSION Repeated , individualized counseling in early childhood aim ed at reducing consumption of saturated fat and cholesterol was effective and feasible and did not restrict growth in circumstances in which children were regularly monitored Background Primary prevention of childhood overweight is an international priority . In Australia 20 - 25 % of 2 - 8 year olds are already overweight . These children are at substantially increased the risk of becoming overweight adults , with attendant increased risk of morbidity and mortality . Early feeding practice s determine infant exposure to food ( type , amount , frequency ) and include responses ( eg coercion ) to infant feeding behaviour ( eg . food refusal ) . There is correlational evidence linking parenting style and early feeding practice s to child eating behaviour and weight status . A focus on early feeding is consistent with the national focus on early childhood as the foundation for life-long health and well being . The NOURISH trial aims to implement and evaluate a community-based intervention to promote early feeding practice s that will foster healthy food preferences and intake and preserve the innate capacity to self-regulate food intake in young children . Methods / Design This r and omised controlled trial ( RCT ) aims to recruit 820 first-time mothers and their healthy term infants . A consecutive sample of eligible mothers will be approached postnatally at major maternity hospitals in Brisbane and Adelaide . Initial consent will be for re-contact for full enrolment when the infants are 4 - 7 months old . Individual mother- infant dyads will be r and omised to usual care or the intervention . The intervention will provide anticipatory guidance via two modules of six fortnightly parent education and peer support group sessions , each followed by six months of regular maintenance contact . The modules will commence when the infants are aged 4 - 7 and 13 - 16 months to coincide with establishment of solid feeding , and autonomy and independence , respectively . Outcome measures will be assessed at baseline , with follow up at nine and 18 months . These will include infant intake ( type and amount of foods ) , food preferences , feeding behaviour and growth and self-reported maternal feeding practice s and parenting practice s and efficacy . Covariates will include sociodemographics , infant feeding mode and temperament , maternal weight status and weight concern and child care exposure . Discussion Despite the strong rationale to focus on parents ' early feeding practice s as a key determinant of child food preferences , intake and self-regulatory capacity , prospect i ve longitudinal and intervention studies are rare . This trial will be amongst to provide Level II evidence regarding the impact of an intervention ( commencing prior to age 12 months ) on children 's eating patterns and behaviours . Trial Registration OBJECTIVE : To assess the relationship between size and growth measurements in infancy to body mass index ( BMI ) at 6 y. DESIGN : A longitudinal observation study on r and omly chosen infants ’ growth and consumption in infancy . Follow-up until the age of 6 y . SUBJECTS : A total of 90 children who were born healthy and full-term . MEASUREMENTS : Weight and height were measured at maternity wards and healthcare centers in Icel and throughout infancy and at 6 y. Food records were made every month during infancy . At 2 , 4 , 6 , 9 and 12 months , food was weighed to calculate food and nutrient intake . RESULTS : Weight gain from birth to 12 months as a ratio of birth weight was positively related to BMI at the age of 6 y in both genders ( B=2.9±1.0 , P=0.008 , and B=2.0±0.9 , P=0.032 for boys and girls , respectively ) . Boys in the highest quartile of protein intake ( E% ) at the age of 9–12 months had significantly higher BMI ( 17.8±2.4 kg/m2 ) at 6 y than the lowest ( 15.6±1.0 kg/m2 , P=0.039 ) and the second lowest ( 15.3±0.8 kg/m2 , P=0.01 ) quartile . Energy intake was not different between groups . Together , weight gain at 0–12 months and protein intake at 9–12 months explained 50 % of the variance in BMI among 6-y-old boys . CONCLUSION : Rapid growth during the first year of life is associated with increased BMI at the age of 6 y in both genders . In boys , high intake of protein in infancy could also contribute to childhood obesity OBJECTIVE To determine whether maternal participation in an obesity prevention plus parenting support ( OPPS ) intervention would reduce the prevalence of obesity in high-risk Native-American children when compared with a parenting support (PS)-only intervention . RESEARCH METHODS AND PROCEDURES Forty-three mother/child pairs were recruited to participate . Mothers were 26.5 + /- 5 years old with a mean BMI of 29.9 + /- 3 kg/m(2 ) . Children ( 23 males ) were 22 + /- 8 months old with mean weight-for-height z ( WHZ ) scores of 0.73 + /- 1.4 . Mothers were r and omly assigned to a 16-week OPPS intervention or PS alone . The intervention was delivered one-on-one in homes by an indigenous peer educator . Baseline and week 16 assessment s included weight and height ( WHZ score and weight-for-height percentile for children ) , dietary intake ( 3-day food records ) , physical activity ( measured by accelerometers ) , parental feeding style ( Child Feeding Question naire ) , and maternal outcome expectations , self-efficacy , and intention to change diet and exercise behaviors . RESULTS Changes in WHZ scores showed a trend toward significance , with WHZ scores decreasing in the PS condition and increasing among the OPPS group ( -0.27 + /- 1.1 vs. 0.31 + /- 1.1 , p = 0.06 ) . Children in the OPPS condition also significantly decreased energy intake ( -316 + /- 835 kcal/d vs. 197 + /- 608 kcal/d , p < 0.05 ) . Scores on the restriction subscale of the Child Feeding Question naire decreased significantly in the OPPS condition ( -0.22+/- 0.42 vs. 0.08+/- 0.63 , p < 0.05 ) , indicating that mothers in the OPPS group were engaging in less restrictive child feeding practice s over time . DISCUSSION A home-visiting program focused on changing lifestyle behaviors and improving parenting skills showed promise for obesity prevention in high-risk Native-American children OBJECTIVE To evaluate the impact of individualized and repeatedly given dietary counseling on fat intake and nutrient intake of children aged 8 months to 4 years . DESIGN Prospect i ve r and omized clinical trial . PARTICIPANTS Children ( N = 1062 ) from 1054 families were r and omized to an intervention ( n = 540 ) or a control ( n = 522 ) group when each child participant was 6 months old . INTERVENTIONS The children in the intervention group were counseled to reduce their intake of saturated fat and cholesterol but to ensure their adequate energy intake . Dietary issues were discussed with the families of the children in the control group only briefly according to the current practice of well-baby clinics . MAIN OUTCOME MEASURES Food consumption was evaluated by using 3- and 4-day food records that were kept at 5- to 12-month intervals , and nutrient intakes were analyzed with a Micro Nutrica computer program ( Social Insurance Institution , Turku , Finl and ) . RESULTS The intake of fat ( 29 % of the energy intake ) and cholesterol ( 70 mg ) showed no differences between the groups of children at 8 months of age . The fat intake in the children in the intervention group was then continuously 2 % of the energy intake below that of the children in the control group ( P < .001 ) . After the age of 13 months , the cholesterol intake of the children in the control group exceeded that of the children in the intervention group by 20 mg ( P < .001 ) . The children in the intervention group consumed 3 % ( of the energy intake ) less saturated ( P < .001 ) and 1 % ( of the energy intake ) more polyunsaturated fats ( P < .001 ) than did the children in the control group at age 13 months and older . The carbohydrate intake was slightly higher in the children in the intervention group than in the children in the control group . Intakes of vitamins , minerals , and trace elements showed no differences between the 2 groups . CONCLUSIONS The intakes of fat by the children in the intervention and control groups were markedly below values that were recommended for the first 2 years of life . Despite the low intake of fat , the intake of other nutrients fulfilled current recommendations , except for vitamin D and iron . Individualized dietary counseling that led to clear changes in the type of fat intake had a minimal effect on vitamin or mineral intakes OBJECTIVE To investigate the association between birth weight , infant growth rate , and childhood adiposity as a proxy for adult metabolic or cardiovascular risk in a Chinese population with a history of recent and rapid economic development . DESIGN Prospect i ve study in a population -representative birth cohort . SETTING Hong Kong Chinese population . PARTICIPANTS Six thous and seventy-five term births ( 77.5 % successful follow-up ) . Main Exposures Birth weight and growth rate ( change in the weight z score ) at ages 0 to 3 and 3 to 12 months . Main Outcome Measure Body mass index ( BMI ) ( calculated as the weight in kilograms divided by the height in meters squared ) z score at about age 7 years . RESULTS Each unit increase in the weight z score at ages 0 to 3 and 3 to 12 months increased the BMI z score by 0.52 and 0.33 , respectively . Children in the highest birth weight and growth rate tertiles had the highest BMI z scores . In the lowest birth weight tertile , increases in the weight z score at ages 0 to 3 months had a larger effect on the BMI z score in boys ( mean difference , 0.88 ; 95 % confidence interval 0.69 - 1.07 ) than in girls ( mean difference , 0.52 ; 95 % confidence interval , 0.33 - 0.71 ) ; these differences by birth weight , growth rate at ages 0 to 3 months , and sex were significant ( P = .007 ) . CONCLUSIONS Faster prenatal and postnatal growth were associated with higher childhood BMI in a population with a recent history of rapid economic growth and relatively low birth weight , suggesting that maximal growth may not be optimal for metabolic risk . However , there may be a developmental trade-off between metabolic risk and other outcomes OBJECTIVE . Our goal was to test the hypothesis that increased fruit juice intake and parental restriction of children 's eating are associated with increased adiposity gain and whether exposure to nutritional counseling predicted reduced adiposity gain among children . PATIENTS AND METHODS . A sample of parents or guardians of children aged 1 to 4 years who attended 1 of 49 Special Supplemental Nutrition Program for Women , Infants , and Children agencies in New York State were surveyed in 1999 or 2000 ( N = 2801 ) . The survey addressed children 's dietary intake , parental feeding practice s , and parental exposure to nutritional counseling messages to increase fruit , vegetable , and low-fat milk intakes . Each child 's height and weight were measured approximately every 6 months for up to 48 months . A prospect i ve cohort design was used in which survey variables were the predictors and the outcome was change in children 's adiposity , defined as change in age- and gender-st and ardized BMI per month ( ie , BMI z-score slope ) . RESULTS . Controlling for gender and ethnicity , the relationship between juice intake and adiposity gain depended on children 's initial overweight status . Among children who were initially either at risk for overweight or overweight , increased fruit juice intake was associated with excess adiposity gain , whereas parental offerings of whole fruits were associated with reduced adiposity gain . Each additional daily serving of fruit juice was associated with an excess adiposity gain of 0.009 SD per month . Feeding restriction was greater among parents whose children were initially at risk for overweight or overweight compared with those at a healthy weight . Parental exposure to nutritional messages was not associated with reduced child adiposity gain . CONCLUSION . This study supports the Institute of Medicine recommendations to reduce fruit juice intake as a strategy for overweight prevention in high-risk children SamenvattingGewichtsproblemen bij kinderen vormen een snelgroeiend probleem , in het bijzonder bij gezinnen met lage inkomens . Eetgedrag ontwikkelt zich vroeg bij kinderen en wordt gevormd door gezinsleden . De dreumesperiode is een kritische periode om een begin te maken met gezonde eetgewoontes en het ontstaan van overgewicht te voorkomen OBJECTIVE To evaluate the longitudinal impact of dietary counseling on children 's nutrient intake . DESIGN A prospect i ve , r and omized , clinical trial . PARTICIPANTS Children were recruited to the study between December 1 , 1989 , and May 30 , 1992 . At the age of 7 months , children were r and omized to the intervention group ( n = 540 ) or the control group ( n = 522 ) and were followed up until the age of 10 years . Intervention Families in the intervention group have , since r and omization , received regularly individualized counseling about how to modify the quality and quantity of fat in the child 's diet , the goal being an unsaturated-saturated fat ratio of 2:1 . MAIN OUTCOME MEASURES Nutrient intakes between the ages of 4 and 10 years based on annual 4-day food records . RESULTS The fat intake of the intervention children was constantly around 30 % of the calorie ( energy ) intake , while that of the control children was 2 to 3 calorie percentage units higher ( P<.001 ) . The intervention children received 2 to 3 calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage unit more polyunsaturated fats than the control children ( P<.001 for both ) . However , neither group reached the 2:1 goal set for the unsaturated-saturated fatty acid ratio . The vitamin and mineral intakes of the intervention and control children closely resembled each other despite the marked differences in fat intake . CONCLUSION Individualized , biannually given , fat intake-focused dietary counseling that began at the child 's age of 8 months continued to influence favorably the diet of 4- to 10-year-old intervention children without disadvantageous dietary effects , but the 2:1 goal for unsaturated-saturated fat ratio was not reached OBJECTIVE Formula-fed infants gain weight faster than breastfed infants . This study evaluated whether encouraging formula-feeding caregivers to be sensitive to infant satiety cues would alter feeding practice s and reduce infant formula intake and weight gain . DESIGN Double-blind , r and omized educational intervention , with intake and growth measured before ( at 1 to 2 months ) and after ( 4 to 5 months ) the intervention . SETTING Women , Infants , and Children ( WIC ) clinics in Sacramento , California . PARTICIPANTS 836 caregivers of young infants were screened ; 214 were eligible , and 104 agreed to participate . INTERVENTION Intervention subjects received education promoting awareness of satiety cues and discouraging bottles containing more than 6 ounces before 4 months of age ; intervention and control groups received education regarding introduction and feeding of solid food after 4 months of age . MAIN OUTCOME MEASURES Formula intake ( mL/24 hours ) and weight gain ( g/week ) . ANALYSIS Differences between groups evaluated using 2-way analysis of covariance ( ANCOVA ) . RESULTS Sixty-one subjects completed baseline records , 44 attended class , and 38 completed the study . Despite a positive response to the educational intervention , there was no change in bottle-feeding behaviors ( formula intake at 4 to 5 months was more than 1100 mL/day in both groups ) . Infant growth in the intervention group was greater than in the control group ( P < .01 ) , contrary to the hypothesis . CONCLUSIONS AND IMPLICATION S The intervention improved knowledge of the key messages , but further research is needed to underst and barriers to modifying bottle-feeding behaviors OBJECTIVE To identify major sources of energy and 24 nutrients and dietary constituents in the diets of US infants and toddlers and to describe shifts in major nutrient sources as children age . DESIGN Data from 24-hour recalls collected in the 2002 Feeding Infants and Toddlers Study were analyzed to determine the percentage contribution of foods and supplements to total intakes of energy , nutrients , and other dietary constituents . A total of 3,586 unique foods and dietary supplements were reported . Reported foods and supplements were classified into 71 groups based on similarities in nutrient content and use . Nine-hundred seventy-nine food mixtures were disaggregated into their ingredients and ingredients were classified into one of the 71 groups using the same decision rules that guided classification of foods analyzed at the whole food level . SUBJECTS/ SETTING A national r and om sample of 3,022 US infants and toddlers 4 to 24 months of age . STATISTICAL ANALYSES PERFORMED The population proportion formula was used to determine the percentage contribution of each of the 71 groups to total intakes . This was done by summing the weighted amount of a given nutrient provided by a given group for all individuals in the sample and dividing by the total weighted amount of that nutrient consumed by all individuals from all foods and supplements . Groups that provided at least 1 % of the nutrient in question were rank-ordered . Separate tabulations were prepared for three age groups ( 4 - 5 months , 6 - 11 months , and 12 - 24 months ) . RESULTS Infant formula , breast milk , and milk are major contributors of energy and most nutrients in the diets of infants and toddlers . Among toddlers , juices and fruit-flavored drinks are the second and third most important sources of energy . Fortified foods make substantial contributions to intakes of many essential nutrients , and these contributions increase as children age . For example , among toddlers , fortified grain-based foods make substantial contributions to intakes of vitamin A , iron , and folate , relative to foods that are naturally rich in these nutrients . Supplements also make substantial contributions to intakes of vitamins and selected minerals , particularly among toddlers . CONCLUSIONS In assessing dietary intakes of infants and toddlers , dietetics professionals need to carefully consider contributions of fortified foods and supplements . Dietetics professionals should educate caregivers of infants and toddlers about the importance of foods ( rather than just nutrients ) in promoting health and about the importance of early feeding practice s in the development of lifelong eating habits . Caregivers should be encouraged to avoid relying on fortified foods and supplements to meet nutrient needs and educated about the potential risk of excessive intakes . Caregivers of toddlers and infants over 4 to 6 months of age who are consuming solid foods should be encouraged to feed a wide variety of fruits , vegetables , and whole grains , as well as foods naturally rich in iron OBJECTIVE To determine whether a rapid rate of weight gain in early infancy is associated with overweight status in childhood . DESIGN Prospect i ve , cohort study from birth to age 7 years . SETTING Twelve sites across the United States . PARTICIPANTS Twenty-seven thous and , eight hundred ninety-nine ( 27 899 ) eligible participants born at full term between 1959 and 1965 . MAIN OUTCOME MEASURE Overweight status at age 7 years , defined by a body mass index above the 95th percentile of the Centers for Disease Control and Prevention reference data . RESULTS In the 19 397 participants with complete data ( 69.6 % ) , the prevalence of overweight status at age 7 years was 5.4 % . The rate of weight gain during the first 4 months of life ( as 100 g/month ) was associated with being overweight at age 7 years , after adjustment for several confounding factors : odds ratio : 1.38 ; 95 % confidence interval : 1.32 - 1.44 . This association was present in each birth weight quintile , and remained significant after adjustment for the weight attained at age 1 year ( odds ratio : 1.17 ; 95 % confidence interval : 1.11 - 1.24 ) . CONCLUSIONS A pattern of rapid weight gain during the first 4 months of life was associated with an increased risk of overweight status at age 7 years , independent of birth weight and weight attained at age 1 year . These findings may lead to new hypotheses regarding the cause of childhood obesity , which may contribute to our underst and ing of this increasing public health problem in the United States |
11,154 | 23,440,263 | All medication classes improved impairment related to AR , but between-treatment comparisons were limited because of different assessment s. Intranasal steroids improved risk outcomes associated with asthma and obstructive sleep apnea .
Small single studies suggested possible effects of oral antihistamines on asthma and sleep-disordered breathing .
Treatment of AR , particularly with intranasal steroids , improves disease control in children by reducing disease-associated impairment and risk .
All AR medications with proved efficacy probably improve impairment , paralleling symptom reduction .
Intranasal steroids may reduce the likelihood of comorbidities that increase health care use . | IMPORTANCE Although the question of whether early diagnosis and treatment of pediatric allergic rhinitis ( AR ) improve disease control is important , a more crucial question is whether we can evaluate the effect of treatment on disease control using an impairment-risk model .
OBJECTIVE To conduct a systematic review evaluating application of a control model based on domains of impairment and risk ( similar to that used for asthma ) in pharmacotherapy for children with AR . | Allergic rhinitis ( AR ) is highly prevalent in children . Olopatadine , 0.6 % nasal spray ( olopatadine ) is approved for the relief of seasonal allergic rhinitis ( SAR ) symptoms in children 6 years of age and older . The objective of this study is to provide a comprehensive report of all clinical studies conducted with olopatadine in children with SAR . A pooled analysis was conducted of 2 r and omized , double-blind , 2-week , IRB-approved studies that compared olopatadine with placebo ( 1 spray/nostril twice-daily ) in patients 6 - 11 years of age with SAR . Assessment s included the reflective total nasal symptom score ( rTNSS ) and total ocular symptom score ( rTOSS ) , the Pediatric Rhinoconjunctivitis Quality -of-Life Question naire ( PRQLQ ) , and the Caregiver Treatment Satisfaction Question naire for Allergic Rhinitis ( CGTSQ-AR ) . Safety results were reported for these studies in combination with a pediatric pharmacokinetic study . Olopatadine was superior to placebo for mean decrease in rTNSS ( p = 0.0012 ) and rTOSS ( p = 0.0094 ) , mean decrease in overall PRQLQ score ( p = 0.0003 ) , and mean summary CGTSQ AR score ( p = 0.0013 ) ; ( n = 944 ) . The most frequently reported treatment-related events in the olopatadine group were epistaxis and dysgeusia ( bad taste ) ( n = 1,046 ) . For SAR treatment in patients 6 - 11 years of age , olopatadine was superior to placebo in reducing the symptoms of SAR , improving quality of life , and satisfying caregivers . Olopatadine is a safe and effective treatment for SAR patients as young as 6 years of age and it has been demonstrated to reduce disease impact on the lives of these children and their families Fluticasone propionate ( FP ) is a topical corticosteroid with minimal systemic activity . We examined safety and compared the efficacy of FP aqueous nasal spray , 200 micrograms every day with loratadine tablets , 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a r and omized , double-blind , parallel-group study . Nasal and eye symptoms were recorded daily on a 4-point ( 0 to 3 ) scale . A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP ( p < 0.0001 ) . Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores . No differences were found for eye irritation symptoms ( p = 0.14 ) . Morning and evening nasal peak inspiratory flow ( PIF ) was recorded daily by 57 subjects . FP treatment was associated wit significantly higher PIF values than loratadine both morning ( p = 0.0051 ) and evening ( p = 0.0036 ) . A greater improvement over 4 weeks was observed for PIF morning values in the FP group ( p = 0.008 ) but not for evening values ( p = 0.358 ) . Statistically significant correlations were found for nasal blockage and PIF in the morning ( r = -0.54 , p = 0.0001 ) and in the evening ( r = -0.46 , p = 0.008 ) Olopatadine ( OLO ) nasal spray 0.6 % is indicated for treatment of seasonal allergic rhinitis ( SAR ) in subjects > or = 12 years of age . This study was design ed to present the results of two studies that evaluated the efficacy , safety , and pharmacokinetics ( PK ) of OLO in children with allergic rhinitis ( AR ) . These were multicenter , double-blind , r and omized , parallel-group studies in subjects 6 to < 12 years of age ( study 1 ) and 2 to < 6 years of age ( study 2 ) with SAR ( study 1 ) or AR ( study 2 ) . In study 1 , nasal and ocular symptoms were scored for efficacy , and study 2 included PK analyses . In both studies , subjects were evaluated based on physical/nasal examinations and adverse events ( AEs ) . Overall , 1188 subjects ( study 1 ) and 132 subjects ( study 2 ) were r and omized , respectively . OLO ( 1 or 2 sprays/nostril , b.i.d . ) was superior to vehicle in the percent decrease in reflective total nasal symptom scores ( p < or = 0.0120 ) . OLO 1 spray/nostril b.i.d . was also superior to vehicle in the percent decreases in reflective total ocular symptom scores ( p < or = 0.0084 ) , change from baseline in Pediatric Rhinoconjunctivitis Quality -of-Life Question naire scores ( p < or = 0.0377 ) , Caregiver Treatment Satisfaction Question naire scores ( p < or = 0.0450 ) , and proportions of subjects reporting improvements in Subject Global Assessment s ( p = 0.0035 ) . The most frequently reported treatment-related events in the OLO group were bad/bitter taste and epistaxis . In subjects 6 to < 12 years of age , OLO was superior to vehicle in the treatment of SAR . In subjects 2 to < 12 years of age , OLO had an overall low rate of AEs and low systemic exposure tion of both CP and cisplatin . Hypersensitivity to mannitol was reported as a cause of apparent hypersensitivity to cisplatin . 6 In case 2 the result of a skin test with mannitol was negative , whereas the result of a skin test with the commercial formulation containing CP and mannitol was positive , suggesting that CP was solely responsible for the hypersensitivity reaction . In addition to the clinical tolerance induced by the desensitization protocol , skin responses to intradermal CP diminished . As shown in Table I , the ratio between wheal sizes of CP and histamine decreased more than 3.5 times after the desensitization . The observation of wheal- and -flare responses becoming negative has already been described in penicillin desensitization . 7 This phenomenon supports an antigen-specific desensitization . The rate at which the drug concentration increases in the extracellular fluid seems to be the most important factor in a successful outcome of desensitization . As suggested by our two patients , this rate can differ in each individual case . We conclude that the 4-hour desensitization protocol may not be suitable for all patients allergic to CP , whereas a modified prolonged protocol seems to be more tolerable . Until further data have been accumulated , the short protocol may be at tempted initially but should be replaced by the prolonged protocol if adverse effects appear . The prolonged protocol seems to be both safe and efficacious with regard to anti tumor activity BACKGROUND We wondered whether short-term coseasonal sublingual immunotherapy ( SLIT ) can reduce the development of asthma in children with hay fever in an open r and omized study . OBJECTIVE We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever . METHODS One hundred thirteen children aged 5 to 14 years ( mean age , 7.7 years ) with hay fever limited to grass pollen and no other clinical ly important allergies were r and omized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or st and ard symptomatic therapy . All of the subjects had hay fever symptoms , but at the time of study entry , none reported seasonal asthma with more than 3 episodes per season . Symptomatic treatment was limited to cetirizine , loratadine , nasal budesonide , and salbutamol on dem and . The hay fever and asthma symptoms were quantified clinical ly . RESULTS The actively treated children used less medication in the second and third years of therapy , and their symptom scores tended to be lower . From the second year of immunotherapy , subjective evaluation of overall allergy symptoms was favorable in the actively treated children . Development of asthma after 3 years was 3.8 times more frequent ( 95 % confidence limits , 1.5 - 10.0 ) in the control subjects . CONCLUSIONS Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever BACKGROUND Concern has been directed at the relative sedating properties of lipophilic and lipophobic antihistamines , but few studies have sought to determine the comparative benefit of seasonal allergic rhinitis ( SAR ) treatments in controlling symptoms and consequently improving alertness . OBJECTIVE To compare the relative contributions of fluticasone propionate aqueous nasal spray and loratadine in enhancing daytime performance in 8- to 17-year-old children . METHODS All participants had a documented history of SAR , positive response to a skin prick ( wheal 3-mm greater than negative control or equal to the positive control ) for seasonal aeroallergens , and clinical ly identifiable symptoms at the time of r and omization . Following confirmation during baseline of current SAR symptoms , participants were r and omized to 1 of the 2 treatments and returned 2 weeks later for evaluation of symptom control , quality of life , attention , reaction time , and memory . RESULTS Children in the fluticasone propionate aqueous nasal spray group but not the loratadine group demonstrated improvement in nasal symptoms , nasal quality of life score , and composite verbal memory . No differences were identified on any scores from the Conners Continuous Performance Test . CONCLUSIONS Treatments that most effectively control SAR symptoms are also likely to provide the greatest benefit to children whose daytime functioning , including their capacity to learn at school , is compromised by their illness BACKGROUND Nasal obstruction is recognized as an important cause of sleep disordered breathing . Congestion of the nasal mucosa and obstruction are common symptoms of allergic rhinitis . Daytime sleepiness is a common finding in symptomatic allergic rhinitis . Effective therapy of the nasal congestion of allergic rhinitis should alter sleep patterns in patients with symptomatic allergic rhinitis . OBJECTIVE To measure objective changes in polysomnograms ( sleep studies ) of children with allergic rhinitis before and after therapy with intranasal budesonide and to measure changes in the quality of life of these patients during treatment . METHODS Open clinical trial with objective measurements ( polysomnography ) and subjective data ( Rhinitis Quality of Life Question naire [ RQLQ ] ) . Evaluations were performed before , during , and at completion of therapeutic intervention . RESULTS The 14 studied children tolerated the procedures and treatment without problems . The mean number of sleep arousals per hour ( all apneas and hypopneas ) decreased from a baseline of 8.4 to 1.2 ( P = .005 ) after treatment . The change was mainly in hypopneic episodes ( 7.5 - 0.9 , P = .003 ) . Objective responses on the RQLQ showed improvements consistent with improved sleep and lessened rhinitis symptoms . CONCLUSIONS Decreasing the nasal congestion associated with allergic rhinitis can improve sleep measured by objective sleep studies and lead to improvement in daytime quality of life BACKGROUND Children with allergic rhinitis are likely to develop asthma . OBJECTIVE The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis . METHODS From 6 pediatric allergy centers , 205 children aged 6 to 14 years ( mean age , 10.7 years ) with grass and /or birch pollen allergy but without any other clinical ly important allergy were r and omized either to receive specific immunotherapy for 3 years or to an open control group . All subjects had moderate to severe hay fever symptoms , but at inclusion none reported asthma with need of daily treatment . Symptomatic treatment was limited to loratadine , levocabastine , sodium cromoglycate , and nasal budesonide . Asthma was evaluated clinical ly and by peak flow . Methacholine bronchial provocation tests were carried out during the season(s ) and during the winter . RESULTS Before the start of immunotherapy , 20 % of the children had mild asthma symptoms during the pollen season(s ) . Among those without asthma , the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis ( odds ratio , 2.52 ; P < .05 ) . Methacholine bronchial provocation test results improved significant in the active group ( P < .05 ) . CONCLUSION Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis BACKGROUND There has been no study comparing the long-term effects of ketotifen , oxatomide , and cetirizine for the treatment of perennial allergic rhinitis among children . OBJECTIVE We conducted a study to compare the efficacy of the three agents for the treatment of perennial allergic rhinitis among children . METHODS The study consisted of a double-blind , placebo-controlled , r and omized design , comprising 69 perennial allergic rhinitis patients with mite allergy , aged 6 to 12 years , r and omly assigned to 1 of 4 test treatment groups for 3 months : 19 in the cetirizine group ( 10 mg daily ) , 18 in the ketotifen group ( 1 mg , twice daily ) , 16 in the oxatomide group ( 1 mg/kg , twice daily ) , and 16 in the placebo group . We used the nasal symptom score of diary card and the Pediatric Rhinoconjunctivitis Quality of Life Question naire and eosinophil cation protein peripheral blood total eosinophil count and immunoglobulin E level , eosinophil proportion from a nasal smear , and nasal peak expiratory flow rate to evaluate the effect of the four agents . RESULTS Cetirizine was significantly more effective at reducing the mean rhinorrhea score compared with oxatomide for both weeks 8 and 12 ( P < 0.01 ) . Before the end of week 12 , cetirizine was significantly more effective than ketotifen ( P < 0.01 ) . Cetirizine and oxatomide significantly decreased the mean Pediatric Rhinoconjunctivitis Quality of Life Question naire score compared with the placebo for week 12 ( P < 0.05 ) . CONCLUSIONS Cetirizine was more effective than oxatomide and ketotifen for the relief of nasal congestion and rhinorrhea , and was responsible for significantly decreasing the eosinophil representation of a posttreatment nasal smear Allergic rhinitis ( AR ) and asthma coexist frequently and a dual treatment is recommended by prescribing topical nasal plus oral inhaled corticosteroids . The purpose of this study was to assess the efficacy of a nasally inhaled corticosteroid aim ing at concomitant control of AR and asthma . A controlled trial was conducted among 60 patients with AR and asthma , aged 6–18 years , who were r and omized into two groups . During 8 weeks , the experimental group ( 30 patients ) received exclusively fluticasone propionate hydrofluoroalkane ( FP‐HFA ) inhaled through the nose ( mouth closed ) using a large volume spacer attached to a face mask . The comparison group ( 30 patients ) received a nasal spray of isotonic saline plus oral inhalation of FP‐HFA through a mouthpiece attached to the same spacer . Clinical scores for AR and asthma , nasal inspiratory peak flow ( NIPF ) , and spirometry were assessed by blinded observers . There was a significant improvement in AR scores and NIPF in the experimental group ( P ≤ 0.01 ) up to week 8 , when a worsening was observed after the intervention was interrupted . Asthma symptoms score , forced expiratory volume (FEV)1 , and FEF25−75 % were not statistically different between groups at the baseline visit or along follow‐up visits ( P ≥ 0.20 ) . Prebronchodilator FEV1 ( % predicted value ) improved by 10 % in both groups , comparing values at inclusion with those obtained at the end of follow up . Our results suggest that nasally inhaled FP‐HFA through a spacer may control AR and asthma in children and adolescents . This approach is likely to result in higher compliance , lower costs , and fewer side effects The 28‐item Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) has strong measurement properties but for large clinical trials , surveys and practice monitoring , where high efficiency is important , a shorter question naire is needed To compare the safety and efficacy of fluticasone propionate aqueous nasal spray ( FPANS ) and oral ketotifen in children aged 2 - 4 years with perennial rhinitis . A r and omized , multicentre , double-blind , double dummy , placebo-controlled study . Paediatric patients between the ages of 2 - 4 years with perennial rhinitis . Rhinitis symptoms score ( parent-rated ) , clinical evaluation of symptoms ( investigator-rated ) and adverse event profiles during the treatment period . Patients treated with FPANS had a significant reduction in both the total night-time rhinitis symptom assessment for weeks 4 - 6 ( p-value 0.036 ) , and the total daytime rhinitis symptom score over the same period ( p-value 0.049 ) . Generally , except for nasal itching/rubbing over weeks 1 - 3 , the patients taking FPANS had lower recorded symptom scores for all individual symptoms measured . Nasal blockage , in particular , was significantly reduced over the 4 - 6 week period ( p-value 0.027 ) . The overall investigator-rated clinical evaluation showed substantial improvement or improvement in nine of 12 of the children taking FPANS compared with four of 14 taking ketotifen . Finally , there were no reports of serious adverse events , the incidence of drug-related adverse events was low and there was no statistical difference between the groups . FPANS may be an appropriate treatment to control the symptoms of rhinitis in children between 2 and 4 years old BACKGROUND Experimental data demonstrate that mite allergy is characterized by persistent chronic inflammation , even during asymptomatic periods . This suggests that long-term continuous treatment be included in the global strategy of allergy treatment . OBJECTIVE We conducted a study to evaluate whether regularly administered cetirizine reduces allergic symptoms and drug prescriptions in children with mite allergy . METHODS In this double-blind , r and omized , placebo-controlled study , two parallel groups of 10 children with mite allergy ( mean age : 6.5 years ) received either cetirizine or placebo daily for 6 months . Participants were allowed to take rescue medications for rhinitis and /or mild asthma . The symptoms ( nasal itching , sneezing , obstruction , rhinorrhea , conjunctival itching , lacrimation , conjunctival hyperemia , cough , wheezing , and chest tightness ) were recorded on a diary card . The intake of cetirizine ( as additional symptomatic treatment ) , antibiotics , acetaminophen , beta2-agonists , inhaled and systemic corticosteroids was also recorded . RESULTS Symptom scores and drug consumption were significantly lower ( P < 0.05 ) in the cetrizine-treated group versus the placebo group . The greatest reductions were in cetirizine itself , inhaled corticosteroids , beta2-agonists , and antibiotics . No side effects were reported in either group . CONCLUSIONS In mite-allergic children , cetirizine administered daily for prolonged periods decreases symptoms of and drug prescriptions for allergic rhinitis and asthma compared with symptomatic treatment Studies evaluating newer antihistamines in children are few . Levocetirizine is a potent and highly selective H1-antihistamine with a proven efficacy in adults . Primary objective was to assess the efficacy of levocetirizine 5 mg once-daily in reducing seasonal allergic rhinitis ( SAR ) symptoms , as measured by Total Four Symptom Score ( T4SS = sum of sneezing , rhinorrhea , nasal and ocular pruritus ) , over the first 2 wk of treatment . Efficacy over 4 and 6 wk of treatment , effect on nasal congestion and on health-related quality of life as measured by PRQLQ ( Paediatric Rhinoconjunctivitis Quality of Life Question naire ) were among the major secondary objectives . A double-blind , r and omized , placebo-controlled study including 177 children with a documented SAR ( to grass and /or weed ) for at least a year and having a mean baseline T4SS > or = 6 ( out of 12 ) . Children evaluated daily the severity of T4SS and nasal congestion on a scale from 0 ( absent ) to 3 ( severe ) . PRQLQ responses were assessed on a scale from 0 ( not bothered ) to 6 ( extremely bothered ) and analysed descriptively . Global evaluation of disease evolution judged by investigators , parents and children was made on a scale from 1 ( marked worsening ) to 7 ( marked improvement ) . For the primary objective , levocetirizine was statistically highly superior to placebo with a difference in adjusted means of 1.29 ( 95 % CI : 0.66 - 1.92 ) in favour of levocetirizine ( p < 0.001 ) . The effect of levocetirizine was almost twice that of placebo ( 94.1 % relative improvement over placebo ) . Nasal congestion was improved with levocetirizine reaching maximum difference to placebo of 0.31 ( p < 0.05 ) , a relative improvement over placebo of 77.5 % . PRQLQ scores at week 2 improved with levocetirizine more than with placebo ( 0.85 vs. 0.51 , respectively ) remaining larger after 4 and 6 wk of treatment . In the study , 84.3 % , 80.9 % , 80.9 % of children had their disease evolution rated as slightly-to-markedly improved by , respectively , the investigators , the parents and children themselves . Incidence of treatment-emergent adverse events was similar in both groups ( 33.7 % with levocetirizine ; 30.7 % with placebo ) . No child in the levocetirizine group discontinued treatment because of adverse events . The 6-wk duration of this study was longer than the usual 2 - 4-wk duration for similar studies and shows that levocetirizine controls SAR symptoms in children over the entire pollen season Cetirizine ( Zyrtec ) is a potent and long-acting second-generation histamine H1- receptor antagonist for the treatment of allergic disease , such as allergic rhinitis and chronic idiopathic urticaria , in adult and child . It is a racemic mixture of levocetirizine ( Xyzal ) and dextrocetirizine . The purpose of this present study was to compare the efficacy of cetirizine , levocetirizine and placebo for the treatment of pediatric perennial allergic rhinitis . 74 perennial allergic rhinitis patients , aged 6 to 12 years old , assigned to 1 of 3 treatment groups for 12 weeks r and omly . The effects of the three agents were compared with the Pediatric Rhinoconjunctivitis Quality of Life Question naire ( PRQLQ ) and Total Symptom Score ( TSS ) by diary . Nasal peak expiratory flow rate ( nPEFR ) and laboratory examinations including serum immunoglobulin E level , eosinophil cationic protein ( ECP ) , blood eosinophil counts and eosinophil percentage in a nasal smear were evaluated among the three groups . The results revealed that both cetirizine and levocetirizine improved TSS in comparison with the placebo group , and ceterizine appeared to be more efficacious than levocetirizine at week 8 and week 12 . The PRQLQ score showed significant decreased both in cetirizine and levocetirizine group , but there was no statistic significant difference between both groups . The eosinophil proportion in a nasal smear significantly decreased among the cetirizine in comparison with the placebo group but there was no statistic significant in levocetirizine groups . Both cetirizine and levocetirizine showed significant improvement in nPEFR in comparison with the placebo group , and ceterizine appeared to be more efficacious than levocetirizine . The 12-week treatment program showed that cetirizine was more effectious than levocetirizine H1-receptor antagonists are considered central to the treatment of atopic dermatitis (AD)-associated pruritus and are widely used in the treatment of AD despite a lack of double-blind , r and omized clinical trials . In this study we analyzed the effects of the long-term use of cetirizine on the severity , natural history , and treatment of AD . In the prospect i ve , multi-country , double-blind , r and omized , placebo-controlled Early Treatment of the Atopic Child ( ETAC ) study , 817 infants ( 12 - 24 months of age ) who suffered from AD at study entry and with a history of atopic disease in a parent or sibling were treated for 18 months with either cetirizine ( 0.25 mg/kg ) or placebo twice daily . All concomitant medications for the treatment of AD were allowed but had to be recorded by the investigator in the case report form ; the concomitant use of H1-antihistamines was discouraged . The primary end-point for efficacy was the onset of asthma . Secondary parameters of efficacy , however , were the consumption of concomitant medications for AD ( topical and systemic treatment ) and the severity of symptoms related to AD , which was rated with the AD scale , SCORAD . The severity of AD , as measured by SCORAD , decreased significantly ( p < 0.001 ) over the study period ( 18 months ) in both groups . Other oral H1-antihistamines were significantly more often used in the placebo group than in the cetirizine group ( 24.9 % vs. 18.6 % , p = 0.03 ) . The number of infants who developed urticaria during the study period was significantly lower with cetirizine treatment ( placebo group : 16.2 % ; cetirizine group : 5.8 % ; p < 0.001 ) . For the treatment of AD , mild topical corticosteroids ( class I , e.g. hydrocortisone ) were used in 41.6 % of the patients ( placebo group 41.6 % , cetirizine group 41.7 % ) and moderate-to-potent topical corticosteroids ( class II , III , IV ) in 55.0 % ( respectively 56.4 % and 53.5 % ) . The duration of the use of topical moderate-to-potent corticosteroids differed between the cetirizine group and the placebo group ( mean percentage of days : placebo 25.2 , median 2.4 ; cetirizine mean 18.8 , median 0.95 p = 0.067 , Mann-Whitney test , not statistically significant ) . In sub-groups of infants with a SCORAD of > or= 25 , this cortico-sparing effect was statistically significant ( placebo 35.1 vs. 25.8 in the cetirizine group ; p = 0.014 , Mann-Whitney test ) . In conclusion , in view of the proven safety of cetirizine , the use of this drug might help to reduce the duration and the amount of moderate-to-strong topical corticosteroids used in the treatment of infants and children with AD . However , further studies design ed with the primary end-point of AD are clearly indicated to confirm the benefits of the use of H1-antihistamines in the management of AD BACKGROUND The objectives of the study were to evaluate impairment in quality of life in 12- to 17-year-old patients with seasonal allergic rhinoconjunctivitis and to develop and test a question naire suitable for evaluating change in quality of life during clinical trials . METHODS Patients were asked to identify physical and emotional impairments associated with allergic rhinoconjunctivitis . The result ant question naire was tested for responsiveness and validity in a clinical trial in which fluticasone nasal spray and loratadine were compared for treatment of ragweed pollen-induced rhinoconjunctivitis . Eighty-three patients , 12 to 17 years of age , with grass- or ragweed-induced hayfever participated in the instrument development phase . They were recruited for the study from an allergy clinic and local schools and recreational organizations . Two hundred forty patients with ragweed hayfever participated in the clinical trial and provided quality of life data . RESULTS The survey showed that in addition to local symptoms , patients experienced impairment of quality of life because of systemic symptoms , activity limitations , and emotional and practical problems . The result ant question naire has 25 items in six domains . In the clinical trial responsiveness was demonstrated by the question naire 's ability to detect change over time and differences between treatments . Construct validity was demonstrated by moderate to strong relationships between changes in diary symptom scores and quality of life . CONCLUSIONS The items identified by 12- to 17-year-old patients were not identical to those previously identified by adults . This suggests that impairment of quality of life may not be the same in the two groups and that it is appropriate to have a question naire specifically design ed for adolescent rhinoconjunctivitis clinical trials BACKGROUND Budesonide aqueous nasal spray is a topical corticosteroid which at doses of 64 to 256 microg once daily has been found to be effective in the treatment of seasonal allergic rhinitis in adults and children . OBJECTIVE This study was conducted to determine the efficacy of budesonide aqueous nasal spray , 128 microg once daily , in children with perennial allergic rhinitis . METHODS This double-blind , r and omized , placebo-controlled , parallel-group , multicenter study compared the efficacy and safety of budesonide aqueous nasal spray , 128 microg once daily intranasally , with placebo in 202 patients ( aged 6 to 16 years ) with perennial allergic rhinitis . Efficacy was evaluated daily by measurement of peak nasal inspiratory flow ( PNIF ) , nasal symptom scores over 12 hours , and an overall evaluation of treatment efficacy . In a subset of patients ( n = 76 ) , quality of life was measured by vali date d question naires . RESULTS Budesonide , 128 microg once daily , was significantly more effective than placebo in improving the PNIF , combined and individual nasal symptom scores , and the overall evaluation of treatment efficacy . The onset of action was found to occur within the first 12-hour time interval evaluated for combined nasal symptoms and within 48 hours for PNIF . Budesonide was associated with reduced percentage of eosinophils in brush sample s and reduced intake of rescue medication in comparison with placebo . Quality of life scores were reduced , but the differences did not reach significance . CONCLUSIONS Budesonide aqueous nasal spray , 128 microg once daily , is effective in children with perennial allergic rhinitis . Efficacy was demonstrated within 12 hours Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness . This improvement with therapy may be secondary to anti-inflammatory effects , leading to a reduction of inflammatory mediators , or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance . We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed . The pooled data of budesonide , flunisolide , and fluticasone demonstrated significantly decreased nasal congestion , sleep problems , and sleepiness in treated patients . The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep ( P < .01 ) and daytime somnolence ( P = .01 ) . Thus , topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms The st and ard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth . Although this therapy is highly effective , and side‐effects are few and mild , it may be possible further to improve the therapeutic index and patient compliance with the treatment . In the present study , we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma . In principle , it results in an airway deposition of the corticosteroid similar to that of inhaled allergens . Twenty‐four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol , attached to a spacer device , in a double‐blind , placebo‐controlled , crossover study . Compared with placebo , budesonide treatment result ed in a significant reduction of nasal symptoms ( P<0.01 ) and of asthma symptoms ( P<0.05 ) , and in an increase of nasal peak inspiratory flow ( P<0.001 ) and of oral peak expiratory flow ( P=0.01 ) . There were no differences between budesonide and placebo in local side‐effects , such as dry nose , nosebleed , and hoarseness . We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children , but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side‐effects |
11,155 | 16,428,031 | It was concluded that there is a lack of rigorous studies in this area and that only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans | Anxiety is a prominent indication for herbal medicine .
This systematic review was therefore aim ed at summarising the evidence for or against the anxiolytic efficacy of such treatments . | Abstract . Rationale : Ayahuasca is a South American psychoactive beverage that contains the naturally occurring psychedelic agent N , N-dimethyltryptamine ( DMT ) . This " tea " has been used for centuries in religious and medicinal context s in the rain forest areas of South America and is presently gaining the attention of psychedelic users in North America and Europe . Objectives : In the present study , the psychological effects and tolerability of ayahuasca were assessed . Methods : Three increasing doses of encapsulated freeze-dried ayahuasca ( 0.5 , 0.75 , and 1.0 mg DMT/kg body weight ) were administered to six healthy male volunteers with prior experience in the use of this tea , in a single-blind crossover placebo-controlled clinical trial . Results : Ayahuasca produced significant dose-dependent increases in five of the six subscales of the Hallucinogen Rating Scale , in the LSD , MBG , and A scales of the Addiction Research Center Inventory , and in the " liking " , " good effects " and " high " visual analogue scales . Psychological effects were first noted after 30–60 min , peaked between 60–120 min , and were resolved by 240 min . The tea was well tolerated from a cardiovascular point of view , with a trend toward increase for systolic blood pressure . Modified physical sensations and nausea were the most frequently reported somatic-dysphoric effects . The overall experience was regarded as pleasant and satisfactory by five of the six volunteers , while one volunteer experienced an intensely dysphoric reaction with transient disorientation and anxiety at the medium dose and voluntarily withdrew from the study . Conclusions : Ayahuasca can be described as inducing changes in the perceptual , affective , cognitive , and somatic spheres , with a combination of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previously reported for intravenously administered DMT A herbal tea ( called an abafado in Brazil ) prepared from the dried leaves of lemongrass was administered to healthy volunteers . Following a single dose or 2 weeks of daily oral administration , the abafado produced no changes in serum glucose , urea , creatinine , cholesterol , triglycerides , lipids , total bilirubin , indirect bilirubin , GOT , GPT , alkaline phosphatase , total protein , albumin , LDH and CPK . Urine analysis ( proteins , glucose , ketones , bilirubins , occult blood and urobilinogen ) as well as EEG and EKG showed no abnormalities . There were slight elevations of direct bilirubin and of amylase in some of the volunteers , but without any clinical manifestation . These results taken together indicate that lemongrass as used in Brazilian folk medicine is not toxic for humans . The eventual hypnotic effect of lemongrass was investigated in 50 volunteers who ingested sample s of lemongrass and a placebo under double-blind conditions . The parameters ( i.e. sleep induction , sleep quality , dream recall and rewakening ) did not show any effect of lemongrass as compared to the placebo . Eighteen subjects with high scores of trait-anxiety were su bmi tted to an anxiety-inducing test following taking lemongrass or placebo under double-blind conditions . Their anxiety levels were similar , indicating that the abafado of the plant does not have anxiolytic properties . It is concluded that lemongrass , one of the most popular Brazilian herbal medicines , used for its alleged CNS-depressant effects , is atoxic but lacks hypnotic or anxiolytic properties OBJECTIVE Passionflower ( Passiflora incarnata ) is a folk remedy for anxiety . A double-blind r and omized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder . METHODS The study was performed on 36 out- patients diagnosed with GAD using DSM IV criteria . Patients were allocated in a r and om fashion : 18 to the Passiflora extract 45 drops/day plus placebo tablet group , and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial . RESULTS Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder . No significant difference was observed between the two protocol s at the end of trial . Oxazepam showed a rapid onset of action . On the other h and , significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam . CONCLUSION The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder , and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage . A large-scale trial is justified The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates . Thirty-six out patients with generalized anxiety disorder ( DSM III-R ) , after a 2-week wash-out , were r and omized to one of the following three treatments for 4 weeks ( n = 12 per group ) : valepotriates ( mean daily dose : 81.3 mg ) , diazepam ( mean daily dose : 6.5 mg ) , or placebo . A parallel , double-blind , flexible-dose , placebo-controlled design was employed . No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale ( HAM-A ) or in the trait part of the state-trait anxiety inventory ( STAI-trait ) . Moreover , the three groups presented a significant reduction in the total HAM-A scores . On the other h and , only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait . Although the principal analysis ( HAM-A between group comparison ) found negative results ( probably due to the small sample size in each group ) , the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety . However , since the number of subjects per group was very small , the present results must be viewed as preliminary . Thus , further studies addressing this issue are warranted The aim of this r and omised double-blind multi-centre parallel group comparative study was to investigate the efficacy and tolerability of a new st and ardised fresh-plant extract obtained from the shoot tips of St. John 's wort ( Hypericum perforatum L. ) in the treatment of mild to moderate depression . 348 out- patients ( 259 female , 89 male ) with mild to moderate depression were recruted by 12 psychiatrc specialty practice s and 26 general practice s. The patients took during 6 weeks 3 times a day 1 tablet of a Hypericum preparation st and ardised to either 0.17 mg ( 114 patients ) , 0.33 mg ( 115 patients ) , or 1 mg ( 119 patients ) total hypericin per day ( Hyperiforce ) . The main outcome measure was the Hamilton Psychiatric Rating Scale for Depression ; additional measures were the Hospital Anxiety and Depression Scale and the Clinical Global Impression . At the end of treatment , a reduction in the average Hamilton Depression score from an initial 16 - 17 to 8 - 9 , i.e. a relative reduction of about 50 % , was observed in all groups ( 280 patients , par protocol analysis ) . The response rates were 62 % , 65 % and 68 % , respectively ( 348 patients , intention to treat analysis ) . Overall , the intergroup comparison revealed no significant differences . Tolerability was excellent , with mild adverse reactions probably causally related to the treatment occurring in only 7 of the 348 patients ( 2 % ) . This Hypericum preparation is effective in all three doses and is well tolerated Scutellaria lateriflora is an herbal medicine with long-st and ing traditional use as a relaxing nervine . There has been controversy in the literature with regards to its efficacy , and this study was design ed to clarify its effectiveness in reducing anxiety , one of the phytotherapeutic indications . A double blind , placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects . The use of phytomedicines for the treatment of anxiety is review ed , as is the published literature on S. lateriflora and its putative toxicity SUMMARY Objective : To assess the clinical efficacy of a neurotonic component containing fixed quantities of two plant extracts ( Crataegus oxyacantha and Eschscholtzia californica ) and magnesium versus placebo in mild-to-moderate anxiety disorders with associated functional disturbances , under usual general practice prescription conditions . Research design and methods : A total of 264 patients ( 81 % female ; mean age : 44.6 years ) presenting with generalised anxiety ( DSM-III-R ) of mild-to-moderate intensity ( total Hamilton anxiety scale score between 16 and 28 ) were included in a double-blind , r and omised , placebo-controlled trial . Patients were r and omly assigned to two groups : 130 received the study drug ( Sympathyl ) , and 134 a placebo ( two tablets twice daily for 3 months ) . Efficacy and safety data were recorded before first administration and 7 , 14 , 30 , 60 and 90 days after start of treatment . Sympathyl is produced and marketed by Laboratoire Innotech International , Arcueil , France . Main outcome measures : Efficacy was assessed by ( a ) change in Hamilton anxiety scale total and somatic scores ; ( b ) change in patient self- assessment ; ( c ) number and percentage of responsive subjects ( reduction of at least 50 % in Hamilton or self- assessment score ) ; and ( d ) the physician 's clinical global impression . Tolerance was assessed by undesirable events spontaneously reported by the patients over the study period . Results : Total and somatic Hamilton scale scores and subjective patient-rated anxiety fell during treatment , indicating clinical improvement . The decrease was greater in the study drug than in the placebo group . End of treatment clinical improvement , as measured by the mean difference between final and pre-treatment scores , was , for the study drug and placebo groups respectively : −10.6 and −8.9 on the total anxiety score ( p = 0.005 ) ; −6.5 and −5.7 on the somatic score ( p = 0.054 ) ; and −38.5 and −29.2 for subjectively assessed anxiety ( p = 0.005 ) . The risk/benefit ratio as judged by the investigating physicians was also significantly greater in the study drug than in the placebo group . In all , 15 patients ( 11.5 % ) in the study drug group and 13 patients ( 9.7 % ) in the placebo group experienced 22 and 15 adverse events , respectively . Undesirable events were mainly mild or moderate digestive or psychopathological disorders . Conclusions : The preparation containing fixed quantities of Crataegus oxyacantha , Eschscholtzia californica , and magnesium proved safe and more effective than placebo in treating mild-tomoderate anxiety disorders The authors studied the acute effects of " Guaraná " , when compared to caffeine and placebo , ( double blind study ) on cognition , anxiety and sleep in 30 normal volunteers . Although results were negative it can not be concluded that " Guaraná " is harmless . Other studies shall be undertaken , administering " Guaraná " on a long term basis , as popularly procl aim ed Abstract . Rationale : Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals . However , the effects on human cognition are inconclusive . Objective : The current study examined the chronic effects of an extract of B. monniera ( Keenmind ) on cognitive function in healthy human subjects . Methods : The study was a double-blind placebo-controlled independent-group design in which subjects were r and omly allocated to one of two treatment conditions , B. monniera ( 300 mg ) or placebo . Neuropsychological testing was conducted pre-(baseline ) and at 5 and 12 weeks post drug administration . Results : B. monniera significantly improved speed of visual information processing measured by the IT task , learning rate and memory consolidation measured by the AVLT ( P<0.05 ) , and state anxiety ( P<0.001 ) compared to placebo , with maximal effects evident after 12 weeks . Conclusions : These findings suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory |
11,156 | 22,426,876 | The results of this systematic review suggest that PFMT with BF is not more effective than other conservative treatments for female PFM dysfunction | Biofeedback ( BF ) has been widely used in the treatment of pelvic floor dysfunctions , mainly by promoting patient learning about muscle contraction with no side effects .
However , its effectiveness remains poorly understood with some studies suggesting that BF offers no advantage over the isolated pelvic floor muscle training ( PFMT ) .
The main objective of this study was to systematic ally review available r and omized controlled trials assessing the effectiveness of BF in female pelvic floor dysfunction treatment . | Objective To assess the effect of pelvic floor education after vaginal delivery on pelvic floor characteristics in nulliparous women . Methods We examined 107 nulliparas during pregnancy and at 9 weeks and 10 months after vaginal delivery . Methods used included a question naire , clinical examination , perineosonography , urethral pressure profiles , and intravaginal and intra-anal pressure recordings during pelvic floor contraction . After the second examination , the women were assigned in alternating manner to either 12 sessions of pelvic floor exercises with biofeedback and electrostimulation ( n = 51 ) or no training ( n = 56 ) . The two groups were compared at the third examination . Results Stress urinary incontinence incidence decreased in 2 % of control subjects compared with 19 % of women who underwent pelvic floor education ( P = .002 ) , whereas the incidence of fecal incontinence ( 5 % versus 4 % , P = 1 ) and the percentage of women who recovered predelivery pelvic floor contraction strength ( 33 % versus 41 % , P = .4 ) were no different . We observed no significant differences in bladder neck position and mobility , urethral functional length , maximal urethral closure pressure , pressure transmission ratio , residual area of continence at stress st and ing , or intravaginal or intra-anal pressures during pelvic floor contraction between groups at the third examination . Conclusion Pelvic floor education , begun 2 months postpartum , significantly reduced the incidence of stress urinary incontinence , but not fecal incontinence or weak pelvic floor . Similarly , bladder neck behavior , urodynamic characteristics , intravaginal or intra-anal pressures during pelvic floor squeezing also were not modified Background and aims A subgroup of constipated patients complain of absent or diminished sense of wanting to defecate , suggesting that one of the causes of constipation is impaired rectal sensation . Electrical stimulation therapy ( EST ) has recently been used to treat patients with urinary and /or fecal incontinence . This study evaluated the efficacy of EST in constipated patients , especially those with impaired rectal sensation . Patients and methods Of the 130 patients with functional constipation as defined by Rome II criteria , 22 patients who had impaired rectal sensation ( rectal desire threshold volume ≥ 90 ml ) on an anorectal manometry were selected . We treated 12 with EST and 10 with biofeedback therapy ( BFT ) according to a r and omized order . Results Overall symptoms of patients significantly improved after each therapy in both groups . Interestingly , frequency of sense of wanting to defecate improved only after EST . On objective findings there was significant improvement in anal residual pressures on attempted defecation only after BFT solely . On the other h and , rectal sensory threshold volumes for desire and urge to defecate and maximal tolerated volume improved significantly only in the EST group . Conclusion Our findings show that the efficacy of EST can be comparable to BFT in a subgroup of constipated patients , especially those with impaired rectal sensation . EST might be considered as an adjunctive therapeutic modality for the management of functional constipation with impaired rectal sensation Background and aims A r and omised trial was undertaken to compare the clinical and functional results of two novel transanal stapled techniques in patients with outlet obstruction syndrome . Material s and methods Ninety-six females with outlet obstruction were treated with medical therapy and biofeedback for 2 months ; 67 non-responders were evaluated by the Constipation Scoring and Continence Grading Systems , clinical examination , endoscopy , dynamic defecography , anorectal manometry , transanal ultrasound and anal EMG , and 50 of them , all affected with descending perineum , intussusception and rectocele , were r and omly assigned to two groups and operated on : 25 patients ( mean age 53.2±15.3 years ) underwent a single Stapled Trans-Anal Prolapsectomy , associated with Perineal Levatorplasty ( STAPL Group ) , and the other 25 ( mean 54.6±14.2 years ) underwent a double Stapled Trans-Anal Rectal Resection ( STARR Group ) . Patients were followed-up for a mean period of 23.4±5.1 months in STAPL Group and 22.3±4.8 in STARR Group . Results STARR Group showed a significantly ( p < 0.0001 ) lower pattern of postoperative pain and a greater decrease ( P = 0.0117 ) of the rectal sensitivity threshold volume ; otherwise , no differences were found in operative time , hospital stay , or time of inability to work . Complications included delayed healing of the perineal wound ( ten ) , dyspareunia ( five ) , urinary retention ( two ) and stenosis ( one ) in STAPL Group , and urge to defecate ( four ) , transitory incontinence to flatus ( two ) , urinary retention ( two ) , bleeding ( one ) and stenosis ( one ) in STARR Group . All constipation symptoms significantly improved without worsening of anal continence and with excellent/good outcome at 20 months in 76 and 88 % of patients of STAPL Group and STARR Group , respectively . Seven patients of STAPL Group had a little residual rectocele , while both intussusception and rectocele were corrected in all patients of STARR Group . Neither operation modified anal pressures or caused lesions of anal sphincters . Conclusions Both techniques are safe and effective in the treatment of outlet obstruction ; nevertheless , the double Stapled Trans-Anal Rectal Resection seems to be preferable due to less pain , absence of dyspareunia , reduced rectal sensitivity threshold volume and absence of residual rectocele at defecography Abstract BACKGROUND : A prospect i ve , three-armed , r and omized , controlled trial was performed to assess whether pelvic floor exercises with biofeedback using anal manometry or transanal ultrasound are superior to pelvic floor exercises with feedback from digital examination alone in terms of continence , quality of life , physiologic sphincter strength , and compliance . Its secondary objectives were to assess whether there are any differences in these outcomes between biofeedback with transanal ultrasound vs. anal manometry and to correlate the physiologic measures with clinical outcome . METHODS : One hundred twenty patients with mild to moderate fecal incontinence were r and omized into one of three treatment groups : biofeedback with anal manometry , biofeedback with transanal ultrasound , or pelvic floor exercises with feedback from digital examination alone . Commencing one week after an initial 45-minute assessment session , patients attended monthly treatments for a total of five sessions . Each session lasted 30 minutes and involved sphincter exercises with biofeedback that involved instrumentation or digital examination alone , and patients were encouraged to perform identical exercises twice per day between outpatient visits . RESULTS : One hundred two patients ( 85 percent ) completed the four-month treatment program . Across all treatment allocations , patients experienced modest but highly significant improvements in all nine outcome measures during treatment , with 70 percent of all patients perceiving improvement in symptom severity and 69 percent of patients reporting improved quality of life . With the possible exception of isotonic fatigue time , there were no significant differences between the three treatment groups in compliance , physiologic sphincter strength , and clinical or quality -of-life measures . Correlations between physiologic measures and clinical outcomes were much stronger with ultrasound-based measures than with manometry . CONCLUSIONS : Although patients in this study who completed pelvic floor exercises with feedback from digital examination achieved no additional benefit from biofeedback and measurement with transanal ultrasound or manometry , it may be that the guidance received through digital examination alone offered patients in the pelvic floor exercise group an effective biofeedback mechanism . Contrary to our hypothesis , the use of transanal ultrasound offered no benefit over manometry , but the use of ultrasound for isotonic fatigue time and isometric fatigue contractions provided potentially important physiologic measures that require further study . This study has confirmed , through a large sample of patients , that pelvic floor retraining programs are an effective treatment for improving physiologic , clinical , and quality -of-life parameters in the short term Purpose This study was design ed to determine whether biofeedback is more effective than diazepam or placebo in a r and omized , controlled trial for patients with pelvic floor dyssynergia-type constipation , and whether instrumented biofeedback is necessary for successful training . Methods A total of 117 patients participated in a four-week run-in ( education and medical management ) . The 84 who remained constipated were r and omized to biofeedback ( n=30 ) , diazepam ( n=30 ) , or placebo ( n=24 ) . All patients were trained to do pelvic floor muscle exercises to correct pelvic floor dyssynergia during six biweekly one-hour sessions , but only biofeedback patients received electromyography feedback . All other patients received pills one to two hours before attempting defecation . Diary data on cathartic use , straining , incomplete bowel movements , Bristol stool scores , and compliance with homework were review ed biweekly . Results Before treatment , the groups did not differ on demographic ( average age , 50 years ; 85 percent females ) , physiologic or psychologic characteristics , severity of constipation , or expectation of benefit . Biofeedback was superior to diazepam by intention-to-treat analysis ( 70 vs. 23 percent reported adequate relief of constipation 3 months after treatment , chi-squared=13.1 , P<0.001 ) , and also superior to placebo ( 38 percent successful , chi-squared=5.7 , P=0.017 ) . Biofeedback patients had significantly more unassisted bowel movements at follow-up compared with placebo ( P=0.005 ) , with a trend favoring biofeedback over diazepam ( P=0.067 ) . Biofeedback patients reduced pelvic floor electromyography during straining significantly more than diazepam patients ( P<0.001 ) . Conclusions This investigation provides definitive support for the efficacy of biofeedback for pelvic floor dyssynergia and shows that instrumented biofeedback is essential to successful treatment The effect of exercise on pressure developed by the circumvaginal muscles ( CVM ) in postpartum women was studied . The CVM assessment system described earlier by Dougherty , Abrams , and McKey used an intravaginal balloon device ( IVBD ) developed from an impression and model of the vagina . The system ( IVBD , pressure transducer and strip chart recorder ) provided permanent CVM pressure tracings with high test-re-test reliability ( n = 16 ; r = .85 ) for maximum pressure ( MP ) . The hypothesis in the research reported here was that exercise with and without an IVBD , when compared to no exercise , would result in significantly higher MP and pressure over time ( POT ) . Forty-five healthy PP volunteers were r and omly assigned to a 10-minute per day home training program , for six weeks . The baseline and six-week assessment s consisted of CVM pressure tracings during contraction . Dependent variables were MP ( highest pressure attained ) and POT ( area under the pressure curve ) . Although no significant differences were found between the home training groups , greater improvement was found in the exercise groups . Variability within subjects partly accounts for the results . Pressure changes before and after pregnancy and before and after CVM exercise are demonstrated in a case study . The findings support the use of CVM exercise in the postpartum OBJECTIVE : To estimate whether treatment gains for provoked vestibulodynia participants r and omly assigned to vestibulectomy , biofeedback , and cognitive – behavioral therapy in a previous study would be maintained from the last assessment —a 6-month follow-up — to the present 2.5-year follow-up . Although all three treatments yielded significant improvements at 6-month follow-up , vestibulectomy result ed in approximately twice the pain reduction as compared with the two other treatments . A second goal of the present study was to identify predictors of outcome . METHODS : In a university hospital , 51 of the 78 women from the original study were reassessed 2.5 years after the end of their treatment . They completed 1 ) a gynecologic examination involving the cotton-swab test , 2 ) a structured interview , and 3 ) vali date d pain and sexual functioning measures . RESULTS : Results from the multivariate analysis of variance conducted on the pain measures showed a significant time main effect ( P<.05 ) and a significant treatment main effect ( P<.01 ) , indicating that participants had less pain at the 2.5-year follow-up than at the previous 6-month follow-up . Results from the multivariate analysis of variance conducted on sexual functioning measures showed that participants remained unchanged between the 6-month and 2.5-year follow-up and that there were no group differences . Higher pretreatment pain intensity predicted poorer outcomes at the 2.5-year follow-up for vestibulectomy ( P<.01 ) , biofeedback ( P<.05 ) , and cognitive – behavioral therapy ( P<.01 ) . Erotophobia also predicted a poorer outcome for vestibulectomy ( P<.001 ) . CONCLUSION : Treatment gains were maintained at the 2.5-year follow-up . Outcome was predicted by pretreatment pain and psychosexual factors . LEVEL OF EVIDENCE : Urinary incontinence is one of the most common problems afflicting older adults and a major contributor to healthcare costs for homebound older individuals . The authors conducted a r and omized controlled clinical study examining the effectiveness of biofeedback-assisted pelvic floor muscle training and prompted voiding in treating urinary incontinence in homebound older adults . This article briefly describes the assessment and treatment protocol s utilized during this study and describes their subsequent application to clinical practice within a large urban home health agency BACKGROUND & AIMS Constipation is a common disorder , and current treatments are generally unsatisfactory . Biofeedback might help patients with constipation and dyssynergic defecation , but its efficacy is unproven , and whether improvements are due to operant conditioning or personal attention is unknown . METHODS In a prospect i ve r and omized trial , we investigated the efficacy of biofeedback ( manometric-assisted anal relaxation , muscle coordination , and simulated defecation training ; biofeedback ) with either sham feedback therapy ( sham ) or st and ard therapy ( diet , exercise , laxatives ; st and ard ) in 77 subjects ( 69 women ) with chronic constipation and dyssynergic defecation . At baseline and after treatment ( 3 months ) , physiologic changes were assessed by anorectal manometry , balloon expulsion , and colonic transit study and symptomatic changes and stool characteristics by visual analog scale and prospect i ve stool diary . Primary outcome measures ( intention-to-treat analysis ) included presence of dyssynergia , balloon expulsion time , number of complete spontaneous bowel movements , and global bowel satisfaction . RESULTS Subjects in the biofeedback group were more likely to correct dyssynergia ( P < .0001 ) , improve defecation index ( P < .0001 ) , and decrease balloon expulsion time ( P = .02 ) than other groups . Colonic transit improved after biofeedback or st and ard ( P = .01 ) but not after sham . In the biofeedback group , the number of complete spontaneous bowel movements increased ( P < .02 ) and was higher ( P < .05 ) than in other groups , and use of digital maneuvers decreased ( P = .03 ) . Global bowel satisfaction was higher ( P = .04 ) in the biofeedback than sham group . CONCLUSIONS Biofeedback improves constipation and physiologic characteristics of bowel function in patients with dyssynergia . This effect is mediated by modifying physiologic behavior and colorectal function . Biofeedback is the preferred treatment for constipated patients with dyssynergia Training to contract the abdominal muscles effectively and to relax the pelvic floor during defecation straining helps some patients with severe constipation . Hitherto all such training has used a visible or audible signal of sphincter muscle activity as a biofeedback method to assist in relaxation . A r and omised controlled trial comparing the outcome of muscular training without any biofeedback device with the same training supplemented by an electromyographic ( EMG ) record visible to the patient is reported . Significant symptomatic improvement was noted and electromyographic measurements confirmed a decrease in pelvic floor muscle activity during defecation straining after treatment in both groups . The outcome was similar in the two treatment groups . Muscular coordination training using personal instruction and encouragement without a visual display is thus a potentially successful treatment suitable for outpatient use by paramedical personnel Biofeedback is a method of pelvic floor rehabilitation using a surface electrode inserted into the vagina and a catheter in the rectum . Forty women with genuine urinary stress incontinence were r and omized to compare the efficacy of physiotherapy and physiotherapy in combination with biofeedback . The effect of the treatment was determined by a st and ardized pad-weighing test . Long-term status was determined using a question naire after 2–3 years . Thirty-four women completed the treatment . The study showed a statistically significant better improvement in the biofeedback group . The long-term effect in the biofeedback group seemed better and the patients were more motivated for training afterwards CONTEXT Previous research on urge urinary incontinence has demonstrated that multicomponent behavioral training with biofeedback is safe and effective , yet it has not been established whether biofeedback is an essential component that heightens therapeutic efficacy . OBJECTIVE To examine the role of biofeedback in a multicomponent behavioral training program for urge incontinence in community-dwelling older women . DESIGN Prospect i ve , r and omized controlled trial conducted from April 1 , 1995 , to March 30 , 2001 . SETTING University-based outpatient continence clinic in the United States . PATIENTS A volunteer sample of 222 ambulatory , nondemented , community-dwelling women aged 55 to 92 years with urge incontinence or mixed incontinence with urge as the predominant pattern . Patients were stratified by race , type of incontinence ( urge only vs mixed ) , and severity ( frequency of accidents ) . INTERVENTIONS Patients were r and omly assigned to receive 8 weeks ( 4 visits ) of biofeedback-assisted behavioral training ( n = 73 ) , 8 weeks ( 4 visits ) of behavioral training without biofeedback ( verbal feedback based on vaginal palpation ; n = 74 ) , or 8 weeks of self-administered behavioral treatment using a self-help booklet ( control condition ; n = 75 ) . MAIN OUTCOME MEASURES Reduction in the number of incontinence episodes as documented in bladder diaries , patients ' perceptions and satisfaction , and changes in quality of life . RESULTS Intention-to-treat analysis showed that behavioral training with biofeedback yielded a mean 63.1 % reduction ( SD , 42.7 % ) in incontinence , verbal feedback a mean 69.4 % reduction ( SD , 32.7 % ) , and the self-help booklet a mean 58.6 % reduction ( SD , 38.8 % ) . The 3 groups were not significantly different from each other ( P = .23 ) . The groups differed significantly regarding patient satisfaction : 75.0 % of the biofeedback group , 85.5 % of the verbal feedback group , and 55.7 % of the self-help booklet group reported being completely satisfied with treatment ( P = .001 ) . Significant improvements were seen across all 3 groups on 3 quality -of-life instruments , with no significant between-group differences . CONCLUSIONS Biofeedback to teach pelvic floor muscle control , verbal feedback based on vaginal palpation , and a self-help booklet in a first-line behavioral training program all achieved comparable improvements in urge incontinence in community-dwelling older women . Patients ' perceptions of treatment were significantly better for the 2 behavioral training interventions BACKGROUND & AIMS Behavioral treatment ( biofeedback ) has been reported to improve fecal incontinence but has not been compared with st and ard care . METHODS A total of 171 patients with fecal incontinence were r and omized to 1 of 4 groups : ( 1 ) st and ard care ( advice ) ; ( 2 ) advice plus instruction on sphincter exercises ; ( 3 ) hospital-based computer-assisted sphincter pressure biofeedback ; and ( 4 ) hospital biofeedback plus the use of a home electromyelogram biofeedback device . Outcome measures included diary , symptom question naire , continence score , patient 's rating of change , quality of life ( short-form 36 and disease specific ) , psychologic status ( Hospital Anxiety and Depression scale ) , and anal manometry . RESULTS Biofeedback yielded no greater benefit than st and ard care with advice ( 53 % improved in group 3 vs. 54 % in group 1 ) . There was no difference between the groups on any of the following measures : episodes of incontinence decreased from a median of 2 to 0 per week ( P < 0.001 ) . Continence score ( worst = 20 ) decreased from a median of 11 to 8 ( P < 0.001 ) . Disease-specific quality of life , short-form 36 ( vitality , social functioning , and mental health ) , and Hospital Anxiety and Depression scale all significantly improved . Patients improved resting , squeeze , and sustained squeeze pressures ( all P < 0.002 ) . These improvements were largely maintained 1 year after finishing treatment . CONCLUSIONS Conservative therapy for fecal incontinence improves continence , quality of life , psychologic well-being , and anal sphincter function . Benefit is maintained in the medium term . Neither pelvic floor exercises nor biofeedback was superior to st and ard care supplemented by advice and education PURPOSE : The efficacy of EMG-biofeedback and low-frequency electrical stimulation for the treatment of anal incontinence has not been proven . Our purpose was to evaluate a novel therapeutic concept , termed triple target treatment , which combines amplitude-modulated medium-frequency stimulation and EMG-biofeedback . METHODS : Patients with anal incontinence were r and omly assigned to the triple target regimen or EMG-biofeedback alone for a 9-month treatment period in a multicenter r and omized clinical trial with blinded observers ( ClincialTrials.gov registration number NCT00525291 ) . Primary end points were changes in the Clevel and Clinic score and the adapted St. Mark 's ( Vaizey ) score at 9 months compared with baseline . Secondary end points included therapy acceptance and proportion of patients achieving continence or improvement in grade or frequency of incontinence . RESULTS : We enrolled 158 patients with anal incontinence . The median decrease in the Clevel and Clinic score from baseline to 9 months was 3 points greater for the triple target regimen than for EMG-biofeedback ( 95 % CI , 1–4 ; P = .0024 ) . The improvement was 8 points for the triple target regimen ( 95 % CI , 7–9 ) and 5 points for EMG-biofeedback ( 95 % CI , 4–7 ) . Results were similar for the Vaizey score . Of patients treated for at least 3 months , continence was achieved by 50 % of patients with the triple target regimen and 25.8 % of those with EMG-biofeedback . CONCLUSIONS : The combination of amplitude-modulated medium-frequency electrostimulation with EMG-biofeedback in the triple target regimen is superior to EMG-biofeedback alone in the treatment of anal incontinence . Therapy programs for fecal incontinence are most effective if patients participate for longer than 2 to 3 months OBJECTIVES Our purpose in this study was to determine whether , with balloon feedback treatment , one can obtain results similar to those achieved with electromyographic ( EMG ) feedback treatment , in patients with a functional outlet obstruction ( spastic pelvic floor syndrome ) . METHODS In a r and omized controlled study , 11 patients received EMG biofeedback and nine patients received balloon feedback . Treatment outcome was assessed by st and ard EMG during straining , constipation score , and a st and ard diary with details about complaints . RESULTS Using change scores ( posttreatment score minus pretreatment score ) , we found significantly greater positive changes for EMG feedback at posttreatment and at follow-up . When criteria for good clinical outcome were used , eight of 11 patients treated with EMG feedback appeared to be improved , against two of nine patients treated with balloon feedback . Type of feedback was the only difference between the groups . CONCLUSIONS Alteration of the EMG pattern leads to lessening of complaints , which means that pelvic floor contraction during straining indeed is the cause of the constipation . The results suggest that EMG feedback is more effective than balloon feedback in treating spastic pelvic floor syndrome OBJECTIVE To compare the effect of individual pelvic floor muscle training with and without biofeedback in women with urodynamic stress incontinence METHODS The study was a single , blind , r and omized trial . All women completed 6 months of pelvic floor muscle training comprising three sets of ten contractions three times per day , supervised by a physical therapist . One group trained with a biofeedback apparatus at home , the other without biofeedback . The primary outcome measures were pad test with st and ardized bladder volume and self‐report of severity . RESULTS A total of 103 women were r and omized , and data from 94 women were analyzed . Mean age ( range ) was 46.6 ( 30–70 ) years , and mean ( range ) duration of symptoms was 9.7 ( 1–25 ) years . Seventy women had urodynamic stress incontinence alone , and 24 women reported additional urge symptoms . Women training with and without biofeedback showed a statistically significant reduction in leakage on pad test ( P < .01 ) after 6 months of pelvic floor muscle training . Objective cure ( 2 g or less of leakage ) in the total group was 58 % in women training with and 46 % in women training without biofeedback , and in the subgroup of women with urodynamic stress incontinence alone , 69 % in women training with and 50 % in women training without biofeedback . There was no statistically significant difference between the groups posttreatment in any outcome measure . CONCLUSION Cure rate was high , and the reduction in urinary leakage after treatment was statistically significant in both groups . However , there was no statistically significant difference in the effect of individual pelvic floor muscle training with and without biofeedback Four hundred and thirty seven consecutive patients with problems of motility were referred to , and examined at our third-level unit from 1987 to 1993 . Forty seven ( mean age 36.3 + /- 3.8 , range 5 - 76 years ; 25 females ) fulfilled the established criteria for fecal incontinence . The mean period of total incontinence was 55.4 + /- 7.6 months ( range 6 months to 21 years ) , with episodes of incontinence of 2.4 + /- 0.2 ( range 1 - 7 a day ) . All patients were asked to complete a question naire in order to vali date the incontinence diagnosis . A complete clinical history was obtained from each patient , and they were given laboratory tests , barium enema , recto-sigmoidoscopy , rectal sensitivity tests , recto-anal manometry , and biofeedback without electronic equipment . Twenty one normal subjects were used as a control group . Patients with fecal incontinence showed less rectal sensitivity ( P < 0.01 ) . The spontaneous recto-anal inhibitory reflex was not present in all forty seven . All the patients that completed their treatment were completely cured in a period of 4 + /- 0.5 months ( range 16 days to 15 months ) , and follow-up continued for one to eight years . To sum up , this new therapeutic approach is beneficial independent of age , duration and cause of incontinence . The treatment is patient-friendly and economical . Doctors have changed their attitudes , and the quality of life of the patient has improved dramatically , thus providing clinical signification , and proof of the validity and applicability of this treatment : using biofeedback without electronic equipment in the treatment of fecal incontinence AIMS Several r and omized controlled trials have demonstrated that pelvic floor muscle training is effective to treat stress urinary incontinence . The aim of the present study was to compare muscle strength increase and maximal strength in responders and non-responders to pelvic floor muscle training . MATERIAL S AND METHODS Fifty-two women with urodynamically proven stress incontinence who had participated in a six months r and omized controlled trial on pelvic floor muscle training , mean age 45.4 years ( range 24 - 64 ) , participated in the study . The women were classified as responders and non-responders based on a combination of five effect variables covering urodynamic measurement , pad test with st and ardized bladder volume , and self-reports . Pelvic floor muscle strength was measured with a vaginal balloon connected to a fiber optic micro tip transducer ( Camtech AS , S and vika , Norway ) . RESULTS There was a positive correlation between improvement in PFM maximal strength and improvement measured by leakage index ( r = 0.34 , P < 0.01 ) , and reduction in urinary leakage measured by the pad test ( r = 0.23 , P = 0.05 ) . The total sample of 52 women comprised 21 responders , 18 unclassifiable , and 13 non-responders . There was a statistically significant difference in maximal strength after the training period between responders and non-responders ; 24.0 cm H2O ( 95 % CI:18.1 - 29.9 ) versus 12.7 cm H2O ( 95 % CI : 6.8 - 18.6 ) P < 0.001 ) , and strength increase ; 14.8 cm H2O ( 95 % CI : 8.9 - 20.7 ) versus 5.0 cm H2O ( 95 % CI : 2.6 - 12.6 ) , respectively ( P = 0.03 ) . CONCLUSIONS There was a positive relation between both pelvic floor muscle strength increase and maximal strength , and improvement of stress urinary incontinence PURPOSE : This study was undertaken to assess the effect of biofeedback therapy in patients with constipation and paradoxical puborectalis contraction and to compare two different feedback modes . METHODS : Twenty-six patients were r and omly allocated to either of two feedback modes : anal pressure using a manometry probe or anal sphincter electromyography ( EMG ) using surface electrodes . RESULTS : Six patients were unable to complete their training ; ten patients were retrained using anal manometry and ten patients using EMG . The paradoxical puborectalis contraction disappeared after retraining with manometry feedback in eight of ten patients and with EMG feedback in ten of ten patients . A significant improvement in both bowel function and abdominal symptoms was found after training and a continued improvement at follow-up six months later . Six patients in the manometry group and nine in the EMG group experienced an overall improvement in symptoms . The two feedback methods did not differ in terms of efficacy . CONCLUSIONS : Our results suggest that biofeedback , using either manometry or EMG , is effective in improving symptoms and anorectal function caused by paradoxical puborectalis contraction PURPOSE : The aim of this study was to compare four methods of biofeedback for patients with constipation . METHODS : Thirty-six patients were prospect ively , r and omly assigned to one of four protocol s : 1 ) outpatient intra-anal electromyographic biofeedback training ; 2 ) electromyographic biofeedback training plus intrarectal balloon training ; 3 ) electromyographic biofeedback training plus home training ; or 4 ) electromyographic biofeedback training , balloon training , and home training . All 36 patients received weekly one-hour outpatient biofeedback training . Success was measured by increased unassisted bowel movements and reduction in cathartic use . In all instances patients maintained a daily log in which documentation was maintained regarding each bowel evacuation and the need for any cathartics . RESULTS ; There was a statistically significant increase in unassisted bowel movements for Groups 1 , 2 , and 4 ( P<0.05 ) and a reduction in the use of cathartics in Groups 1 , 2 , and 3 ( P<0.05 ) . CONCLUSION : There was a significant improvement in outcome after all four treatment protocol s for constipation ; however , no significant difference was found among the treatments . Therefore , electromyographic biofeedback training alone is as effective as with the addition of balloon training , home training , or both PURPOSE : This study was design ed to compare prospect ively the effects of augmented biofeedback with those of sensory biofeedback alone on fecal incontinence and anorectal manometry after obstetric trauma . METHODS : A consecutive cohort of 40 females with impaired fecal continence after obstetric anal sphincter injury were recruited from a dedicated perineal clinic . Patients were r and omly assigned to receive either augmented biofeedback or sensory biofeedback alone . All patients were assessed before and after twelve weeks of biofeedback training , using a fecal continence question naire and anorectal manometry . RESULTS : Thirty-nine of 40 females recruited completed the study . Continence scores improved in both treatment groups , but the results were better for those who received augmented biofeedback . Anorectal manometry was unchanged by sensory biofeedback , whereas anal resting and squeeze pressures increased with augmented biofeedback . No change in anal vector symmetry was observed in either group . CONCLUSION : Augmented biofeedback training is superior to sensory biofeedback alone in the treatment of impaired fecal continence after obstetric trauma Pages I-H , Jahr S , Schaufele MK , Conradi E : Comparative analysis of biofeedback and physical therapy for treatment of urinary stress incontinence in women . Am J Phys Med Rehabil 2001;80:494–502 . Objective To compare the effectiveness of an intensive group physical therapy program with individual biofeedback training for female patients with urinary stress incontinence . Design R and omized study of two therapeutic interventions consisting of a specific physical therapy program ( PT ) or biofeedback training ( BF ) daily for 4 wk , followed by a 2-mo , unsupervised home exercise program in both groups in an outpatient clinic of a large university hospital . Forty women , referred by gynecologists for nonoperative treatment of genuine stress incontinence of mild-to-moderate severity , were included . Measurements of daytime/nocturnal urinary frequency and subjective improvement of incontinence were the main outcome measures at initial presentation , after completion of the therapy program , and at follow-up after 3 mo . St and ardized examinations of digital contraction strength , speculum tests , and manometric measurements were documented as secondary outcome measures . Results In the PT group , the daytime urination frequency decreased 22 % after 4 wk of therapy and 19 % after 3 mo ( P < 0.05 ) from baseline . The nocturnal urination frequency was reduced by 66 % after 4 wk of therapy and 62 % after 3 mo ( P < 0.001 ) . In the BF group , the daily urination frequency decreased 10 % after 4 wk of therapy and 5 % after 3 mo ( P > 0.05 ) . The nocturnal urination frequency declined 36 % after 4 wk of therapy and 66 % after 3 months ( P < 0.05 ) . Subjective assessment after 3 mo showed that in the PT group , 28 % of patients were free of incontinence episodes , 68 % reported improved symptoms ( incontinence episodes improved by > 50 % ) , and 4 % were unchanged . In the BF group , 62 % were free of incontinence episodes , and 38 % were improved . Results of the digital contraction strength assessment s , speculum tests , and manometric measurements showed statistically significant improvement in all variables in both groups after 3 months . Conclusion Four weeks of both intensive group physical therapy or individual biofeedback training followed by an unsupervised home exercise program for 2 mo are effective therapies for female urinary stress incontinence and result in a significantly reduced nocturnal urinary frequency and improved subjective outcome . Only group physical therapy result ed in reduced daytime urinary frequency . BF therapy result ed in a better subjective outcome and higher contraction pressures of the pelvic floor muscles Purpose Anal electric stimulation has been described as effective for fecal incontinence in several case series , but no study has addressed possible mechanism of benefit . We wished to examine whether anal electric stimulation , using an anal probe electrode , used on a daily basis at home for eight weeks , in the absence of any adjunctive exercises or advice , would improve symptoms of fecal incontinence and anal sphincter pressures when compared with “ sham ” electric stimulation . Methods Ninety patients ( 9 males , 81 females ) , with median age of 55 ( range , 30–77 ) years were r and omized , 47 to active anal stimulation at 35 Hz and 43 to “ sham ” stimulation at 1 Hz . Outcome measures included a one-week bowel diary , symptom question naire , manometry , and patients ' evaluation of outcome . Results Seventy patients completed the study . On an intention-to-treat analysis , there was no difference between the two groups on any of the outcome measures after eight weeks . Of those who completed stimulation , 44 ( 63 percent ) felt the stimulation had improved their continence . Those with intact anal sphincters were not likely to rate their change more positively than those with sphincter disruption ( P = 0.71 ) . Median patient rating of bowel control increased from 3 of 10 before stimulation to 5 of 10 after stimulation ( P = 0.001 ) . Conclusions Eight weeks of anal electric stimulation was rated by patients as having improved their bowel control to a modest extent . There was no statistically significant difference detected between the groups , suggesting that 1 Hz was as effective as 35 Hz . This raises the possibility that the main effect is not sphincter contraction but sensitization of the patient to the anal area , or simply the effect of intervening per se . Home electric stimulation is a relatively cheap and generally well-tolerated therapy in the conservative treatment of fecal incontinence Aim / Background Cholestyramine may improve fecal incontinence , but its use has not been assessed . We report our experience with the use of cholestyramine in the treatment of fecal incontinence . Material s and methods Twenty-one patients ( 19 female , mean age 65 years ) with fecal incontinence ( ≥1 episode/week ) received cholestyramine along with biofeedback therapy ( group A ) . Stool frequency , stool consistency ( Bristol scale ) , number of incontinent episodes , satisfaction with bowel function ( VAS ) , and anorectal physiology were assessed at 3 months and at 1 year after treatment . Data were compared with a matched group of 21 incontinent subjects ( 19 female , mean age 64 years ) who received biofeedback alone ( group B ) . Results At 3 months and at 1 year , group A patients showed decreased stool frequency ( p < 0.01 ) , stool consistency ( p = 0.001 ) , and number of incontinent episodes ( p < 0.04 ) . In contrast , stool frequency ( p = 0.8 ) and stool consistency ( 0.23 ) were not different from baseline in group B subjects . In both groups , there was improvement in the satisfaction with bowel function ( p < 0.05 ) , anal sphincter pressures ( p < 0.05 ) and ability to retain saline infusion ( p < 0.05 ) . Mean dose of cholestyramine used was 3.6 g ; 13 subjects ( 62 % ) required dose titration , and 7 ( 33 % ) subjects reported minor side effects . Conclusion Cholestyramine is safe and useful adjunct for the treatment of diarrhea and fecal incontinence . Most patients require small doses , and dose titration is important . The improvement in stool characteristics favors a drug effect , over and above the benefits of biofeedback therapy PURPOSE This study was conducted to investigate the effectiveness of pelvic floor muscle exercise using biofeedback and electrical stimulation after normal delivery . METHODS The subjects of this study were 49 ( experimental group : 25 , control group : 24 ) postpartum women who passed 6 weeks after normal delivery without complication of pregnancy , delivery and postpartum . The experimental group was applied to the pelvic muscle enforcement program by biofeedback and electrical stimulation for 30 minutes per session , twice a week for 6 weeks , after then self-exercise of pelvic floor muscle was done 50 - 60 repetition per session , 3 times a day for 6 weeks . Maximum pressure of pelvic floor muscle contraction ( MPPFMC ) , average pressure of pelvic floor muscle contraction ( APPFMC ) , duration time of pelvic floor muscle contraction ( DTPFMC ) and the subjective lower urinary symptoms were measured by digital perineometer and Bristol Female Urinary Symptom Question naire and compared between two groups prior to trial , at the end of treatment and 6 weeks after treatment . RESULTS The results of this study indicated that MPPFMC , APPFMC , DTPFMC were significantly increased and subjective lower urinary symptoms were significantly decreased after treatment in the experimental group than in the control group . CONCLUSIONS This study suggested that the pelvic floor muscle exercise using biofeedback and electrical stimulation might be a safer and more effective program for reinforcing pelvic floor muscle after normal delivery BACKGROUND Urinary stress incontinence is a common , disruptive and potentially disabling condition in which the subject complains of involuntary leakage on effort or exertion or on sneezing or coughing . AIM This study was performed in order to compare the effects of interferential current and biofeedback applications on incontinence severity in patients with urinary stress incontinence . In addition , pelvic muscle strength and quality of life as important parameters in these subjects were investigated . METHODS In this prospect i ve , r and omised , controlled study , forty women with moderate intensity of urinary stress incontinence as determined by one-hour pad test were included . Pelvic muscle strength was evaluated by a biofeedback device and quality of life was assessed by a 28-itemed question naire . All of the parameters were evaluated before and after the treatments . Twenty cases underwent interferential current therapy , while pelvic floor exercises via biofeedback were applied in the remaining cases . The treatments lasted 15 minutes per session , three times a week for a total of 15 sessions . RESULTS All of the parameters improved after the treatments in each group ( p < 0.05 ) and both treatment modalities seemed to have similar effects on pad test ( 95 % CI : -1.48 - 4.59 ) , pelvic muscle strength ( 95 % CI : -9.29 -1.78 ) and quality of life ( 95 % CI : -11.91 - 5.31 ) outcomes . CONCLUSIONS Physical therapy modalities used in this trial are applied easily and non invasive . Also , when the finding that no adverse effects were observed during the study period is taken into consideration , it can be concluded that both methods can be used effectively in patients with urinary stress incontinence & NA ; This study compared group cognitive – behavioral therapy ( 12‐week trial ) , surface electromyographic biofeedback ( 12‐week trial ) , and vestibulectomy in the treatment of dyspareunia result ing from vulvar vestibulitis . Subjects were 78 women r and omly assigned to one of three treatment conditions and assessed at pretreatment , posttreatment and 6‐month follow‐up via gynecological examinations , structured interviews and st and ard question naires pertaining to pain ( Pain Rating Index and Sensory scale of the McGill Pain Question naire , vestibular pain index , pain during intercourse ) , sexual function ( Sexual History Form , frequency of intercourse , Information subscale of the Derogatis Sexual Functioning Inventory ) , and psychological adjustment ( Brief Symptom Inventory ) . As compared with pretreatment , study completers of all treatment groups reported statistically significant reductions on pain measures at posttreatment and 6‐month follow‐up , although the vestibulectomy group was significantly more successful than the two other groups . However , the apparent superiority of vestibulectomy needs to be interpreted with caution since seven women who had been assigned to this condition did not go ahead with the intervention . All three groups significantly improved on measures of psychological adjustment and sexual function from pretreatment to 6‐month follow‐up . Intent‐to‐treat analysis supported the general pattern of results of analysis by‐treatment‐received . Findings suggest that women with dyspareunia can benefit from both medical and behavioral interventions BACKGROUND AND PURPOSE This correlational study describes factors that are related to patient compliance with exercise regimens during physical therapy . We investigated whether patient compliance was related to characteristics of the patient or the patient 's illness , to the patient 's attitude , or to the physical therapist 's behavior . SUBJECTS AND METHODS Of a r and om sample of 300 physical therapists in private practice in the Netherl and s , 222 therapists responded to a question naire survey . Eighty-four respondents also made audio recordings . Material s of the study were 1,931 registration forms , 1,837 audio-recorded sessions of physical therapy sessions , and 1,681 patient question naires . RESULTS The results show that the three main factors related to noncompliance were ( 1 ) the barriers patients perceive and encounter , ( 2 ) the lack of positive feedback , and ( 3 ) the degree of helplessness . The first factor , the barriers patients perceive and encounter , shows the strongest relation with noncompliance . The results also show that noncompliance is more strongly related to the characteristics of the illness than to the illness , a bad prognosis is negatively related to compliance , and much hindrance of the complaint is positively related to compliance . There was no difference between men and women with regard to patient compliance , but less educated patients were slightly more compliant than more highly educated patients . CONCLUSION AND DISCUSSION These correlational findings can be used to formulate hypotheses of cause and effect in future clinical research . Future research should take into account the type and efficacy of therapeutic exercise for different diseases . For physical therapy practice , it seems important that physical therapists carefully explore which problems patients encounter in their efforts to comply and that they seek solutions to those problems in mutual cooperation with their patients Although patients ' satisfaction may be high after restorative proctocolectomy the functional results are still far from perfect . Increased bowel frequency and imperfection in continence are common . Pouch volume and anal sphincter status are important determinants for the outcome . The aim of the present study was to evaluate if balloon dilatation of the pouch and sphincter biofeedback training might improve the results . Forty patients with an ileo-pouch anal anastomosis were r and omized into a control and a treatment group . During the interval with a diverting ileostomy , patients in the latter group were subjected to balloon dilatation of the pouch and sphincter biofeedback training by using a manovolumetric technique . All patients were functionally assessed and anorectal manovolumetry performed preoperatively and at regular intervals postoperatively . Follow-up time was at least 12 months . Immediately before ileostomy take down patients in the treatment group showed a significant initial increase in pouch compliance compared with controls . However , a rapid and pronounced increase in pouch volume occurring after ileostomy closure in the control group equalized this initial difference . Anal resting tone and maximum squeezing capacity were at all intervals similar in the two groups . Bowel frequency per 24 h was similar and mucus soiling occurred to a similar extent in both groups , and the overall functional result as assessed according to a scoring system was equal at each interval . Balloon dilatation of the pouch and sphincter exercises appear not to be essential measures in these patients A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence . Subjects were initially allocated to one of two groups ; one group was trained to perceive small rectal volumes ( active retraining ) , the other group carried out the same maneuvers but were not given any information or instruction . Active sensory retraining reduced the sensory threshold from 32±8 to 7±2 ml ( P<0.001 ) , corrected any sensory delay that was present ( P<0.004 ) , and reduced the frequency of incontinence from 5±1 to 1±1 episodes per week ( P<0.01 ) . Sham retraining caused a modest reduction in the sensory threshold ( from 29±9 to 20±8 ; P<0.05 ) but did not significantly reduce the frequency of incontinence . Subsequent strength and coordination training did not significantly improve continence , although at the end of the study , 50 % of patients had no incontinent episodes at all and 76 % of patients had reduced the frequency of incontinence episodes by more than 75 % . This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation . The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up . In conclusion , the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence 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 Abstract PURPOSE : The aim of this study was to assess the long-term clinical and quality of life outcomes for patients after referral to a four-month treatment program for fecal incontinence based on pelvic floor exercises and biofeedback . Secondary objectives were to document patients ’ subsequent treatment activities and their perception of the biofeedback training ; to establish the long-term outcomes and initial predictors for the subset of patients who did not complete the treatment , or who failed to improve during the program ; and to correlate changes in clinical outcome measures and quality of life over time . METHODS : Patients were contacted by telephone to determine their perception of progress subsequent to the treatment program , any subsequent treatment or activities relating to their fecal incontinence , and which aspect of the treatment program they believed was most helpful . St. Mark ’s and Pescatori fecal incontinence scores were also recorded , along with patients ’ self- assessment s of their incontinence severity and quality of life . RESULTS : Eighty-three ( 69 percent ) patients were contacted for interviews at a median of 42 ( range , 26–56 ) months after program completion . At the time of follow-up , patients who completed the program continued to enjoy strongly significant improvements in all outcome measures , with 75 percent perceiving a symptomatic improvement and 83 percent reporting improved quality of life . For many patients , improvement continued subsequent to program completion . Patients whose incontinence scores became worse during treatment still reported improvement in their quality of life and perceived incontinence severity during the same time period ; many experienced some degree of “ catch-up ” in their continence scores during the follow-up period . Fourteen patients ( 17 percent ) went on to have surgery for fecal incontinence ; of these , 6 ( 7 percent ) had a stoma . Twenty ( 24 percent ) regularly took antidiarrheal medication . Thirty program completers ( 41 percent ) were continuing pelvic floor exercises . CONCLUSIONS : This study confirms the long-term improvement in fecal incontinence achieved through treatment with biofeedback and pelvic floor exercises . In this study , patients also continued to improve after treatment completion , possibly because of the strong emphasis placed on patients during treatment to continue the pelvic floor exercises on their own . The poor correlation between quality of life and quantitative scores of fecal incontinence suggests that there are important aspects of continence that are not being appropriately recognized Biofeedback therapy has been proposed as a treatment for fecal incontinence with good , short-term results . PURPOSE : This study was design ed to assess long-term clinical results of biofeedback therapy compared with medical therapy alone and to assess manometric results in patients treated with biofeedback . METHODS : Two groups of incontinent patients were studied . Group 1 consisted of 16 patients ( 3 males and 13 females ; mean age , 59.9 years ) . Etiologies treated by biofeedback included descending perineum syndrome ( 7 ) , postfistula or hemorroidectomy ( 4 ) , and miscellaneous ( 5 ) . Group 2 consisted of eight patients ( two males , six females ; mean age , 62.2 years ) . Etiologies treated with medical treatment alone ( including enema and antidiarrheal therapy ) included descending perineum syndrome ( 3 ) , postfistula or hemorroidectomy ( 2 ) , and miscellaneous ( 3 ) . The incontinence score was initially 17.81±3.27 ( st and ard deviation ) in Group 1 and 17.0±2.77 in Group 2 . Resting pressure of the upper and lower anal sphincter , maximum squeezing pressure , and duration of contraction were not initially different in Groups 1 and 2 but were significantly lower than in the control group of patients without incontinence ( n=12 ; 8 males , 4 females ; mean age , 66.4 years ) ( P<0.05 ) . Follow-up duration was 30 months , with intermediate clinical score at 6 months for Group 1 . RESULTS : After biofeedback therapy , the incontinence score at 30 months was lower in Group 1 ( 14.43±6.35vs.17.81 ±3.27;P<0.035 ) and unchanged in Group 2 ( 18.0±2.72vs.17.0±2.77 ) . However , in Group 1 the score at 6 months was much lower than at 30 months ( 6.31±7.81vs.14.43±6.35;P<0.001 ) . Only the amplitude of voluntary contraction and upper anal pressure ( 51.1 ( range , 27–90)vs36.7 ( range , 20–80 ) mmHg ) were significantly increased ( 81.5 ( range , 55–120)vs.62.1 ( range , 30–90 ) mmHg;P<0.05 ) . CONCLUSION : Biofeedback improved continence at 6 months and at 30 months . However , the score at 6 months was much better , suggesting that the initial good results may deteriorate over a long time . These data suggest that it could be useful to reinitiate biofeedback therapy in some patients Purpose Anismus is a significant cause of chronic constipation . This study came to revive the results of BFB training and BTX-A injection in the treatment of anismus patients . Material s and methods Forty-eight patients with anismus ( 33 women ; mean age 39.6 ± 15.9 ) were included in this study . All patients fulfilled Rome II criteria for functional constipation . All patients underwent anorectal manometry , balloon expulsion test , defecography , and electromyography ( EMG ) activity of the EAS . All patients had non-relaxing puborectalis muscle . The patients were r and omized into two groups . Group I patients received biofeedback therapy , two times per week for about 1 month . Group II patients were injected with BTX-A. Follow-up was conducted weekly in the first month then monthly for about 1 year . Results In the BFB training group , three patients quit before the end of sessions with no improvement ; initial improvement was recorded in 12 patients ( 50 % ) while long-term success was recorded in six patients ( 25 % ) . In the BTX-A group , clinical improvement was recorded in 17 patients ( 70.83 % ) , but the improvement persisted only in eight patients ( 33.3 % ) . There is a significant difference between BTX-A group and BFB group regarding the initial success , but this significant difference disappeared at the end of follow-up . Manometric relaxation was achieved significantly post-BFB and post-BTX-A injection with no significant difference between the two groups . Conclusions Biofeedback training has a limited therapeutic effect on patients suffering from anismus . BTX-A injection seems to be successful for temporary treatment of anismus A r and omized controlled trial was carried out with the purpose to determine the effectiveness of EMG-biofeedback in the treatment of chronically constipated elderly patients with dyssynergic defecation as compared to a control condition characterized by information about the bowel functioning and counseling focused on the behavioural mechanisms involved in the defecation . With this purpose , after an initial assessment period ( 4 weeks ) , 30 chronically constipated elderly patients with dyssynergic defecation ( 11 males , 19 females ) were r and omly assigned to either EMG-biofeedback group ( n = 15 ) or control group ( n = 15 ) . The results shown significant improvements in psychophysiological measures ( EMG-activity during straining to defecate and anismus index ) , as well as in clinical variables ( frequency of defecations per week , sensation of incomplete evacuation , difficulty evacuation level and perianal pain at defecation ) only in the EMG-biofeedback group . The clinical benefits of this behavioural treatment were maintained at the follow-up period 2 months later Objective To correlate changes in vestibular pain thresholds to general pain thresholds in a subgroup of women with provoked vestibulodynia taking part in a treatment study . Methods Thirty-five women with provoked vestibulodynia were r and omized to 4 months ' treatment with either electromyographic biofeedback ( n=17 ) or topical lidocaine ( n=18 ) . Vestibular and general pressure pain thresholds ( PPTs ) were measured and the health survey Short Form-36 ( SF-36 ) was filled out before treatment and at a 6-month follow-up . Subjective treatment outcome and bodily pain were analyzed . Thirty healthy women of the same age served as controls for general PPTs and SF-36 . Results No differences in outcome measures were observed between the 2 treatments . Vestibular pain thresholds increased from median 30 g before to 70 g after treatment in the anterior vestibule ( P<0.001 ) and from median 20 to 30 g in the posterior vestibule ( P<0.001 ) . PPTs on the leg and arm were lower in the patients as compared with controls both before and at the 6-month follow-up . Patients reporting total cure were 3/35 ; 25/35 were improved . The number of patients who frequently reported of other bodily pain was reduced after the treatment . The patients had lower scores for SF-36 ( General Health , Vitality ) before treatment , which was restored at the 6-month follow-up . Discussion Treating provoked vestibulodynia by either topical lidocaine or electromyographic biofeedback increased vestibular pain thresholds , reduced dyspareunia , and improved bodily pain . The patients showed a general hypersensitivity to pressure pain compared with controls and in this study the hypersensitivity did not seem to be affected by treating the superficial dyspareunia 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 Purpose This study came to compare the results of biofeedback retraining biofeedback ( BFB ) , botulinum toxin botulinum type A ( BTX-A ) injection and partial division of puborectalis ( PDPR ) in the treatment of anismus patients . Patients and Methods Consecutive patients treated for anismus fulfilled Rome II criteria for functional constipation at our institution were evaluated for inclusion . Participants were r and omly allocated to receive BFB , BTX-A injection , and PDPR . All patients underwent anorectal manometry , balloon expulsion test , defecography , and electromyography activity of the anal sphincter . Follow up was conducted weekly in the first month then monthly for about 1 year . Study variables included clinical improvement , patient satisfaction , and objective improvement . Results Sixty patients with anismus were r and omized and completed the study . The groups differed significantly regarding clinical improvement at 1 month ( 50 % for BFB , 75%BTX-A injection , and 95 % for PDPR , P = 0.006 ) and differences persisted at 1 year ( 30 % for BFB , 35%BTX-A injection , and 70 % for PDPR , P = 0.02 ) . Constipation score of the patients significantly improved postPDPR and BTX-A injection . Manometric relaxation was achieved significantly in the three groups . Conclusion Biofeedback retraining has a limited therapeutic effect , BTX-A injection seems to be successful for temporary treatment but PDPR is found to be an effective with lower morbidity in contrast to its higher success rate in treating anismus OBJECTIVE The purpose of this study was to examine the effects of combining behavioral treatment and drug treatment for urge incontinence in community-dwelling older women . DESIGN Modified crossover design ( extension of a r and omized clinical trial ) . Eligible subjects were stratified according to type and severity of incontinence and r and omized to behavioral treatment , drug treatment , or a control condition ( placebo ) . Subjects not totally continent or not satisfied after 8 weeks of a single treatment were offered the opportunity to cross over into combined therapy . SETTING A university-based outpatient geriatric medicine clinic . PARTICIPANTS Subjects in the clinical trial were 197 ambulatory , nondemented , community-dwelling women ( age 55 years or older ) with persistent urge urinary incontinence . Thirty-five subjects participated in combined treatment . INTERVENTION One group of subjects received four sessions ( over 8 weeks ) of biofeedback-assisted behavioral training followed by 8 weeks of behavioral training combined with drug therapy ( oxybutynin chloride individually titrated from 2.5 mg to 15 mg daily ) . The second group received drug therapy first , followed by 8 weeks of drug therapy combined with behavioral training . MEASUREMENTS Bladder diaries completed by subjects before and after each treatment phase were used to calculate change in the frequency of incontinent episodes . RESULTS Eight subjects ( 12.7 % ) crossed from behavioral treatment alone to combined behavioral and drug therapy . Additional benefit was seen in improvement from a mean 57.5 % reduction of incontinence with single therapy to a mean 88.5 % reduction of incontinence with combined therapy ( P = .034 ) . Twenty-seven subjects ( 41.5 % ) crossed from drug therapy alone to combined drug and behavioral treatment . They also showed additional improvement , from a mean 72.7 % reduction of incontinence with single therapy to a mean 84.3 % reduction of incontinence with combined therapy ( P = .001 ) . CONCLUSIONS This study shows that combining drug and behavioral therapy in a stepped program can produce added benefit for patients with urge incontinence 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 OBJECTIVE The purpose of this study was to compare intra-anal electromyographic biofeedback alone with intra-anal biofeedback that was augmented with electrical stimulation of the anal sphincter in the treatment of postpartum fecal incontinence . A secondary aim was to examine the impact of the treatment on continence-related quality of life . STUDY DESIGN Sixty symptomatic women were assigned r and omly to receive intra-anal electromyographic biofeedback or electrical stimulation of the anal sphincter once weekly for 12 weeks and to perform daily pelvic floor exercises between treatments . Therapeutic response was evaluated with a symptom question naire to determine continence score , anal manometry , and endoanal ultrasound scanning . Quality of life was assessed before and after treatment with a vali date d question naire . RESULTS Fifty-four women completed the treatment ; 52 women ( 96 % ) had ultrasonic evidence of an external anal sphincter defect . After the treatment , both groups demonstrated significant improvement in continence score ( P < .001 ) and in squeeze anal pressures ( P < .04 ) . Resting anal pressures did not alter significantly . Quality of life improved after the completion of physiotherapy , but there were no differences in outcome between intra-anal electromyographic biofeedback and electrical stimulation of the anal sphincter . CONCLUSION Intra-anal electromyographic biofeedback therapy was associated with improved continence and quality of life in women with altered fecal continence after delivery . The addition of electrical stimulation of the anal sphincter did not enhance symptomatic outcome Stress urinary incontinence is a common problem among women of all ages but may resolve with pelvic floor reeducation in many cases . Compliance to a regimen of pelvic floor muscle exercises is poor and many devices have been produced to make exercising these muscles more effective and interesting . This article describes a study in which two such devices -- vaginal cones and pressure biofeedback -- were compared with pelvic floor exercises alone . The results show that there is no statistically significant difference between the three modalities ; all treatments produced significant improvement in symptoms and quality of life scores Biofeedback ( BF ) training is an accepted therapy in the treatment of faecal incontinence ( FI ) despite a paucity of data demonstrating benefit . This study aims to determine whether BF has any specific effect above and beyond an educational intervention . Twenty-three women with regular and frequent idiopathic FI were r and omized to education and pelvic exercise vs education and BF therapy . Complete data is available for 18 women . Overall , 61 % of participants demonstrated a complete response . There was no difference in response rate between treatment arms . Women with FI demonstrate a good response to treatment with education and exercise and education plus BF thus question ing the specific effect of BF PURPOSE : The aim of the study was to evaluate the effect of perioperative biofeedback training on postoperative continence in patients with rectal prolapse . METHODS : Thirtysix consecutive patients were operated on between 1987 and 1993 . Twenty-nine could be traced for reexamination . Four were excluded because of a recurring prolapse . Anal manometry , assessment of rectoanal sensation , and surface electromyography were performed during the reexamination . From 1987 to 1991 , no perioperative biofeedback training was given ( Group 1 , n=14 ) . Since the beginning of 1992 , incontinent patients were given biofeedback training ( Group 2 , n=11 ) . RESULTS : Continence scores improved in both study groups . Both study groups had equally low resting pressures compared with Group 3 ( controls ) ( 30.6±1 4.9vs.53.0±11.9 mmHg;P<0.001 ) . Anal resting pressure correlated with postoperative continence score , whereas contractile pressures did not ( r=−0.5,P < 0.05 , and r=−0.3,P = not significant , respectively ) . CONCLUSION : Biofeedback therapy can improve the function of external sphincter ; however , the most important reason for postoperative incontinence in rectal prolapse patients is low resting pressure that can not be corrected by biofeedback therapy This paper describes PEDro , the Physiotherapy Evidence Data base . PEDro is a web-based data base of r and omized controlled trials and systematic review s in physiotherapy . It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro . The data base contains bibliographic details and abstract s of most English- language r and omized trials and systematic review s in physiotherapy , and of many trials and review s in other language s. Trials on the data base are rated on the basis of their method ological quality so that users of the data base can quickly identify trials of high quality . Trials and systematic review s are extensively indexed to facilitate search ing . PEDro provides an important information re source to support evidence -based clinical practice 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 Urinary incontinence is a common and costly problem among homebound older adults . This article describes the assessment and management protocol s utilized in a clinical trial examining the effectiveness of behavioral interventions in treating urinary incontinence in homebound older adults . Individuals with urinary incontinence were identified and referred to the study by home care nurses from two large home health agencies . Following in-home assessment , eligible subjects were r and omized to an immediate treatment group or a delayed treatment group ( control group ) . Subjects who were cognitively intact were treated with biofeedback-assisted pelvic floor muscle training , while subjects with cognitive impairments were treated with a program of prompted voiding . Two nurse practitioners assessed and treated subjects participating in the study 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 Purpose Biofeedback is well established as a treatment for fecal incontinence but little is known about factors that may be associated with its effectiveness . This study assessed short-term outcomes , predictors of patients who completed treatment , and predictors of treatment success . Methods This study was a retrospective review of consecutive patients treated with biofeedback at a tertiary referral colorectal clinic during ten years . Clinical , physiologic , and quality of life measures were collected prospect ively at the time of treatment . Regression analysis was performed . Results Of 513 patients , 385 ( 75 percent ) completed the treatment program . Each outcome was improved for more than 70 percent of patients . Incontinence scores decreased by 32 percent ( from 7.5 to 5.2 of 13 ) , patient assessment of continence increased by 40 percent ( from 5.3 to 3.2 of 10 ) , quality of life improved by 89 percent ( from 0.34 to 0.67 of 1.0 ) , and maximum anal sphincter pressure increased by a mean 12 mmHg ( 14 percent ; from 90 to 102 mmHg ) . Patients who did not complete treatment were younger , were more likely to be male , and had less severe incontinence . Treatment success was predicted by completion of all treatment sessions ( odds ratio , 10.34 ; 95 percent confidence interval , 4.46–24.19 ) , female gender ( odds ratio , 4.11 ; 95 percent confidence interval , 1.04–7.5 ) , older age ( odds ratio , 1.02 per year ; 95 percent confidence interval , 1–1.04 ) , and more severe incontinence before treatment ( odds ratio , 1.19 per unit increase in St. Mark ’s score ; 95 percent confidence interval , 1.05–1.34 ) . Conclusions More than 70 percent of patients in this large series demonstrated improved short-term outcomes . Treatment success was more likely in those who completed six training sessions , were female , older , or had more severe incontinence . Patients were less likely to complete treatment if they were male , younger , or had milder incontinence Purpose This study was design ed to evaluate the effect of biofeedback and electrostimulation in a r and omized , clinical trial for the treatment of patients with postdelivery anal incontinence . Methods Forty-nine females who sustained third-degree or fourth-degree perineal rupture with a mean age of 36 ( range , 22–44 ) years were included in the study . The females were r and omized to biofeedback or electrostimulation treatment . Forty females completed the study : 19 in the biofeedback and 21 in the electrostimulation group . Biofeedback or electrostimulation sessions were performed two times daily for eight weeks in each group . Wexner incontinence score , fecal incontinence quality of life scores , and reduced quality of life on visual analog scale were registred before and after treatment . Patients ’ self-rating of treatment effect also was registered in both groups . The primary outcome measure was the Wexner incontinence score . Results There were no differences in treatment effect between groups . Comparing pretreatment status to posttreatment in each group showed no improvement in Wexner score , reduced quality of life , or any of the fecal incontinence quality of life scores . Patients ’ self-rating of the treatment effect , however , showed a subjective improvement of symptoms both in the biofeedback and in the electrostimulation group ( median , 7 vs. 5 . ) Conclusions This study shows that there was no difference in effect between biofeedback and electrostimulation . Neither biofeedback nor electrostimulation treatments improved Wexner incontinence score , reduced quality of life , or fecal incontinence quality of life scores . Both treatments result ed in improvement of patients ’ subjective perception of incontinence control We investigated the effectiveness of pelvic floor muscle ( PFM ) exercises or biofeedback for the treatment of urinary stress incontinence ( USI ) . Fifty patients with USI were included in this r and omized , controlled , prospect i ve study . Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program . The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months . The third group of 10 patients did not have any exercises . The patients were evaluated via pad test , perineometry , digital palpation based PFM strength , incontinence frequency , and visual analog scale based social activity index prior to and 8 weeks after the treatment . The first two groups had significant improvement in USI with respect to the control group ( p < 0.001 ) . The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment ( p < 0.001 ) . PFM exercises are effective for the treatment of USI ; the biofeedback method revealed better PFM strength results with respect to digital palpation In a r and omized , controlled trial comparing biofeedback-assisted behavioral therapy and drug therapy with oxybutynin , both types of therapy were superior to placebo in older , community-dwelling women with urge or mixed incontinence . Behavioral therapy significantly reduced incontinence compared with oxybutynin therapy ( 80.7 % vs 68.5 % , P = 0.04 ) . Patients expressed high levels of satisfaction with behavioral therapy , and 97 % were willing to continue this therapy indefinitely , compared with 55 % receiving drug therapy . Results of recent studies suggest that behavioral therapy without biofeedback or pelvic floor electrical stimulation also results in significant clinical benefits , which should make behavioral therapy a more practical approach in the general practice setting . Statistical analysis showed no significant relationship between posttreatment urodynamic changes and clinical outcomes , and thus , the mechanisms by which behavioral and drug therapies work remain unidentified . In a small trial of combination therapy , patients who received both drug and behavioral therapy experienced significant clinical improvements compared with the effects of monotherapy with either treatment OBJECTIVES To compare electromyography-assisted biofeedback training to pelvic floor muscle training ( PFMT ) alone in patients with female stress urinary incontinence . METHODS A prospect i ve r and omized pilot study was conducted between March 1998 and February 2000 at the university hospital for outpatient care . Participants were women with urodynamically tested stress incontinence aged 31 to 69 years without previous incontinence operations , 30 volunteers altogether . The biofeedback group received an electromyography-guided biofeedback device for home training and the PFMT-alone group trained without any device at home . All patients were advised to practice for 20 minutes per day five times a week for 12 weeks . RESULTS According to the data analysis , muscle forces increased significantly in both supine ( P < 0.001 ) and st and ing ( P < 0.001 ) positions . In the supine position , the increase was significantly higher in the biofeedback group ( P = 0.024 ) . The results showed close to a significant decrease in the leakage index in the biofeedback group ( P = 0.068 ) , but in the PFMT-alone group , no change occurred . With respect to the pad test , the decrease was significant , but it was the same for both groups ( P = 0.907 ) . CONCLUSIONS The findings of this study show that pelvic floor muscle activity is increased and the amount of leaked urine is decreased after 3 months of PFMT . These preliminary results show a significant improvement compared with the PFMT-alone group in PFMT outcome measures in patients using electromyography-assisted biofeedback training Urinary incontinence ( UI ) is a commonly underreported and underdiagnosed condition . The purpose of this trial was to implement and evaluate behavioral management for continence ( BMC ) , an intervention to manage symptoms of UI with older rural women in their homes . Participants were r and omized into BMC or a control group , and 178 were followed for between 6 and 24 months . The intervention involved self-monitoring , bladder training , and pelvic muscle exercise with biofeedback . The primary outcome variable-severity of urine loss-was evaluated by pad test . Secondary variables were episodes of urine loss , micturition frequency , voiding interval , quality of life , and subjective report of severity . Urine loss severity at baseline evaluation was not significantly different in the two groups . But using the generalized linear mixed model analysis , at the four follow-ups , severity of urine loss , episodes of urine loss , quality of life , and subjective report of severity were significantly different . At 2 years the BMC group UI severity decreased by 61 % ; the control group severity increased by 184 % . Self-monitoring and bladder training accounted for most of the improvement . The results support the use of simple strategies based on bladder diaries before implementing more complex treatments PURPOSE : Biofeedback therapy in fecal incontinence has been reported to improve continence in more than 70 percent of patients , but most studies have followed patients for less than two years . METHODS : Patients treated by biofeedback training between 1985 and 1986 were given a question naire in 1991 , as were incontinent patients who had not entered this treatment program . All were asked for the occurrence , frequency , and severity of incontinence events in the past two weeks . Anamnestic and anorectal manometry data from the initial visit were also compared . RESULTS : Eighteen of 24 treated patients and 40 of 71 untreated patients responded . Of those treated by biofeed-back , 78 percent reported episodes of fecal incontinence as compared with 77.5 percent of those not treated by biofeedback . Severity of incontinence , however , was significantly less ( P<0.02 ) in the treatment group ( mean number of events , 0.2/day ) than in those without treatment ( 1/day ) . In biofeedback-treated patients , it was identical with the frequency and severity reported immediately after therapy . No differences were found with respect to initial clinical data and anorectal manometry between both groups . CONCLUSION : Biofeedback training improves continence in patients not only during treatment and within the first two years but also for several years after therapy We compared telemedicine with a conventional outpatient continence service ( CS ) in community-dwelling older women with urge or stress incontinence . After an initial biofeedback-assisted pelvic floor muscle training session , subjects were r and omized to behavioural training for eight weeks via the CS ( n = 27 ) or a telemedicine continence programme ( TCP ) ( n = 31 ) . Participants in both treatment groups experienced significant improvement in their symptoms , namely , a reduction in the number of daily incontinence episodes ( P<0.001 ) and voiding frequency ( P<0.001 ) , while the volume of urine at each micturition increased ( P<0.005 ) . Pelvic floor muscle strength as measured by the Oxford Score also improved ( P<0.005 ) . There were no significant differences in outcomes between the two groups . Thus our findings suggest that videoconferencing is as effective as conventional methods in the management of urinary incontinence |
11,157 | 22,566,267 | Results Access remained the principal determinant of recurrence rates after surgery .
ConclusionS urgical access remains the most important factor that influences outcome after surgery for recurrent pneumothoraces . | AimS urgery for recurrent spontaneous pneumothoraces is one of the most commonly performed procedures in thoracic surgery , but few studies have evaluated the efficacy of the surgical treatment options .
We aim ed to evaluate the influence of the type of pleurodesis on recurrence whilst adjusting for surgical access by systematic review and meta-regression of r and omised and non-r and omised trials . | Surgical treatment of spontaneous pneumothorax can be done through a thoracotomy or a video-thoracoscopic approach . Although the videothoracoscopic technique is currently popular it is not obviously superior to a more traditional axillary thoracotomy approach . We compared our recent experience with both techniques to determine the optimal surgical treatment for spontaneous pneumothoraces . A retrospective review of 79 patients treated surgically ( 34 thoracotomy and 45 thoracoscopy ) for spontaneous pneumothoraces was done . Patients were treated between 1991 and 1997 . Patients older than 60 years of age and those with spontaneous pneumothoraces secondary to generalized pulmonary emphysema were excluded . There were no operative deaths . Recurrence rate [ thoracotomy , two of 34 ; thoracoscopy , three of 45 ( P < 0.89 ) ] , air leak exceeding 7 days [ thoracotomy , three of 34 ; thoracoscopy , three of 45 ( P < 0.73 ) ] , operating room times [ thoracotomy , 54 + /- 26 minutes ; thoracoscopy , 53 + /- 16 minutes ( P < 0.59 ) ] , and postoperative length of stay [ thoracotomy , 5.7 + /- 4.3 days ; thoracoscopy , 4.7 + /- 4.4 days ( P < 0.26 ) ] were not significantly different for the two techniques . We conclude that axillary thoracotomy and videothoracoscopy are equally effective surgical treatments for spontaneous pneumothoraces . A large r and omized trial would be needed to determine whether one approach is truly superior to the other The aim of the present study was to determine the impact of various pleurodesis procedures on post-operative morbidity and late recurrence rate after surgical treatment of V and erschueren ’s stage III primary spontaneous pneumothorax . Between January 2001 and June 2004 , 208 consecutive patients ( 169 male and 39 female ; mean ( range ) age 25 ( 12–39 ) yrs ) were su bmi tted to 220 video-assisted thoracoscopic surgical procedures for primary spontaneous pneumothorax . All patients underwent apical lung resection ; 112 were assigned at r and om to mechanical pleural abrasion ( group A ) and 108 to apical pleurectomy ( group B ) . The two groups of patients showed similar characteristics . No intra- or post-operative deaths occurred . Post-operative morbidity was 6.25 % for group A and 12.9 % for group B ; the two groups exhibited a similar persistent post-operative air leak rate ( 5.3 % in group A and 5.5 % in group B ) , whereas haemothorax was significantly more frequent after apical pleurectomy ( eight ( 7.4 % ) cases ) than after pleural abrasion ( one ( 0.9 % ) case ) . The mean duration of follow-up was 46 ( 24–66 ) months . Late recurrence occurred in five cases ( 4.6 % ) after apical pleurectomy , and in seven ( 6.2 % ) after mechanical pleural abrasion . Mechanical pleural abrasion by video-assisted thoracoscopic surgery is safer than apical pleurectomy in the treatment of primary spontaneous pneumothorax . No differences in late recurrence rate were observed between the two procedures BACKGROUND Although management of spontaneous pneumothorax by video-assisted thoracic surgery ( VATS ) has generally shown superior clinical results to thoracotomy , management of spontaneous pneumothorax by transaxillary minithoracotomy ( TAMT ) has also shown good clinical results . The objective of this study was to compare the clinical results of VATS and TAMT in treating spontaneous pneumothorax . METHODS Sixty-six patients , aged 13 to 81 years , with recurrent , persistent or contralateral spontaneous pneumothorax were involved in this study . Thirty-six patients were treated by VATS and 30 by TAMT . The operating time , the amount of analgesics used on the first postoperative day , the duration of the indwelling chest tube , and the number of recurrences after operation were compared . The follow-up periods of both procedures were from 6 to 24 months . RESULTS Of the 66 patients , 64 were male and 2 were female . The duration of operation , from start of skin incision to insertion of chest tube , was 91.2 + /- 36.8 minutes in VATS and 86.3 + /- 40.9 minutes in TAMT ( p = 0.6061 ) . The amount of analgesics ( keptoprofen ) used was 1.9 + /- 2.3 ampules in VATS and 2.1 + /- 2.9 ampules in TAMT ( p = 0.0883 ) . The duration of indwelling chest tube was 5.0 + /- 4.0 days in VATS and 4.3 + /- 2.1 days in TAMT ( p = 0.3707 ) . The number of recurrences after operation was 4 in VATS and none in TAMT . CONCLUSIONS There were no advantages of VATS over TAMT for management of recurrent , persistent , or contralateral spontaneous pneumothorax in regard to the operating time , the amount of analgesics used on the first postoperative day , the duration of the indwelling chest tube , and the number of postoperative recurrences in patients with apical bullae OBJECTIVE To eluci date whether thoracoscopy for surgical therapy of pneumothorax leads to a reduction of inflammatory responses in comparison with st and ard thoracotomy . DESIGN A prospect i ve r and omized study PATIENTS Eleven patients ( 9 men and 2 women ; median age , 28 years ; range , 21 - 44 years ) were treated by thoracotomy ; 10 patients ( 9 men and 1 woman ; median age , 26 years ; range , 21 - 28 years ) were managed thoracoscopically . The plasma concentrations of the following were determined : polymorphonuclear granulocyte elastase and C-reactive protein as inflammatory parameters and prostanoids ( prostacyclin , thromboxane A2 , prostagl and in F2 alpha , prostagl and in M , and prostagl and in E2 ) as vasoactive parameters . Blood sampling was performed perioperatively and on day 3 after surgery . RESULTS The thoracoscopy group revealed a shorter hospital stay ( 5 vs 7 days ; P < .05 ) and a significantly reduced need for intravenous pain medication within 48 hours ( 1 vs 3 requirements ; P < .01 ) vs the thoracotomy group . The release of inflammatory ( C-reactive protein , P < .01 ) and vasoactive ( prostacyclin and thromboxane A2 , P < .01 ) mediators was less during thoracoscopy compared with st and ard thoracotomy . CONCLUSIONS The thoracoscopic procedure is less invasive when performing wedge resection of apical blebs . With intracavitary management being equivalent to the conventional technique , the curtailed morbidity after thoracoscopic surgery is considered to be related to the minimal trauma associated with the access to lung tissue and the reduced h and ling of lung tissue In a prospect i ve comparison , 60 patients suffering from complicated spontaneous pneumothorax were r and omly allocated to receive treatment by a video-assisted thoracoscopic surgery ( VATS ) technique or by thoracotomy . Thirty patients underwent bullectomy and apical pleurectomy by VATS performed through three 2-cm incisions ( group V ) and 30 patients underwent a similar surgical procedure through a posterolateral thoracotomy ( group T ) . The median operating time was significantly longer in group V ( 45 versus 37.5 minutes ; p < 0.05 ) , but the postoperative analgesic requirement and hospital stay were less than those in group T. On the third postoperative day , the reductions in the forced expiratory volume in 1 second and forced vital capacity were significantly lower in group V than in group T ( p < 0.05 and p < 0.01 , respectively ) . Initial treatment of the spontaneous pneumothorax was effective in 27 patients ( 90 % ) in group V and in 29 patients ( 97 % ) in group T. There have been two late recurrences in group V and one in group T at a median follow-up of 15.1 months and 16.3 months , respectively . Within the study group , 30 consecutive patients presented with primary spontaneous pneumothorax . In this subgroup there was no significant difference in the operating time between VATS and thoracotomy , but postoperative pain , hospital stay , and pulmonary dysfunction were all less for those undergoing VATS . All treatment failures were in the subgroup of 30 consecutive patients who presented with secondary spontaneous pneumothorax , and the hospital stay in this group was prolonged by the use of VATS . We conclude from our findings that VATS is superior to thoracotomy in the treatment of primary spontaneous pneumothorax . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND A prospect i ve , r and omized study was carried out on patients with primary spontaneous pneumothorax , with the aim of determining if video-assisted thoracoscopy is superior to axillary thoracotomy in the surgical treatment of this condition . METHODS Patients were r and omly assigned to two groups ; video-assisted thoracoscopy ( group A ; n = 46 ) and axillary thoracotomy ( group B ; n = 44 ) . All fit the established criteria for surgical indication ( relapse or persistent air leakage after pleural drainage ) . In all cases the treatment consisted of apical segmentectomy of the blebs or dystrophic complex and pleural mechanical abrasion . The study evaluated the following factors : postoperative blood loss , respiratory function ( maximum inspiratory and expiratory pressures , forced expiratory volume in the first second and forced vital capacity ) , postoperative pain ( analog visual scale ) , supplementary doses of analgesics , postoperative complications , hospital stay , and resumption of normal activity . Relapses were evaluated for the minimum period of time of two years . RESULTS No significant differences were found in any of the factors studied in either group . CONCLUSIONS Video-assisted thoracoscopy and axillary thoracotomy offer similar results in the surgical treatment of primary spontaneous pneumothorax . The rate of complication is low and the level of pain is acceptable without long-term sequelae Parietal pleurectomy is the most effective method of preventing a recurrence of spontaneous pneumothorax . Until recently , however , it has required thoracotomy which is associated with significant morbidity . The advent of video-assisted thoracoscopic surgery ( VATS ) has offered a less traumatizing method of performing parietal pleurectomy , but experience in this operation is limited . In this study we compared the operative results of our first twelve patients treated using VATS ( VATS-group ) with twelve consecutive patients operated on via thoracotomy ( T-group ) before we started using VATS . The groups were comparable in terms of age , sex ratio and the length of preoperative pleural drainage . In the VATS-group peroperative blood loss was markedly less , but the mean operative time was 16 min longer than in the T-group . There was practically no difference in the number of opioid dosages given postoperatively between the groups , but the hospital stay was approximately three days shorter in the VATS-group than in the T-group . Inability to work lasted two weeks longer in the T-group than in the VATS-group . In the T-group there were no recurrences of pneumothorax , but in the VATS-group pneumothorax recurred in two patients . They were both treated using a Roeder loop to excise bullae . One patient was reoperated via thoracotomy and another was treated by pleural suction . The initial Finnish experience of VATS-pleurectomy shows that parietal pleurectomy can be performed safely with less morbidity in the treatment of recurrent spontaneous pneumothorax . However , recurrences in the VATS-group underlines the proper selection of technical methods when using this method of treatment OBJECTIVE To present our experience of video-assisted thoracoscopy in the treatment of recurrent spontaneous pneumothorax , and to compare the results with those of a historical control group treated by lateral thoracotomy . DESIGN Prospect i ve evaluation with historical controls . SETTING Teaching hospital , Italy . SUBJECTS 41 Patients with recurrent spontaneous pneumothorax , 20 of whom were treated by video-assisted thoracoscopy and 21 of whom underwent lateral thoracotomy ( historical control group ) . MAIN OUTCOME MEASURES Duration of chest drainage , length of hospital stay , amount of narcotic analgesia required , postoperative complications , and recurrence during follow up . RESULTS The mean ( range ) duration of chest drainage in the group who underwent video-assisted thoracoscopy was 5 days ( 4 - 7 ) compared with 7 days ( 4 - 13 ) in the control group ; the corresponding figures for length of hospital stay were 6 days ( 4 - 8 ) compared with 10 days ( 5 - 16 ) . 3 Patients ( 15 % ) in the thoracoscopy group required parenteral narcotic analgesia compared with 14 ( 66 % ) in the control group , and 2 ( 10 % ) developed minor complications compared with 5 ( 24 % ) . The mean length of follow up was 9 months ( range 1 - 18 ) compared with 26 months ( 19 - 34 ) , and no patient in either group developed a recurrence . CONCLUSION Our early results of treating recurrent spontaneous pneumothorax with video-assisted thoracoscopy have been encouraging , and we have adopted it in preference to lateral thoracotomy |
11,158 | 26,586,384 | there is an evidence of effectiveness of short term PTNS in treatment of non-neurogenic OAB .
PTNS is proven significantly better than sham procedure | AIM to evaluate the effectiveness of short-term PTNS for non-neurogenic OAB in adults systematic ally by comparing with sham procedure and other treatments . | Objective To verify whether the combination of transcutaneous electrical neural stimulation ( TENS ) with oxybutynin in the treatment of women with overactive bladder ( OAB ) would be more effective than isolated treatments . Methods We r and omized 75 women with OAB , in three groups : GI—30 min TENS , twice a week ; GII — daily slow release 10 mg oxybutynin ; and GIII — TENS + oxybutynin ( multimodal ) ; all for 12 weeks . Patients were evaluated with vali date d question naires International Consultation on Incontinence-Short Form ( ICIQ-SF ) , International Consultation on Incontinence-OAB ( ICIQ-OAB ) , Symptom bother , and 3-day Voiding diary at weeks 0 , 12 , and 24 . Results The groups were similar before treatment . After treatment , all groups significantly improved in OAB symptoms and quality of life ( QoL ) . At week 12 , ICIQ-OAB scores were 5.9 , 4.6 , and 2.9 , in groups I , II , and III , respectively , p = 0.01 . At week 24 , GI and GIII kept the scores of the end of treatment ( week 12 ) , while GII increased ICIQ-OAB from 4.6 to 9.2 , p = 0.0001 , ICIQ-SF from 9.8 to 13.3 , p = 0.0006 , and Symptom bother score from 3.4 to 7.0 , p = 0.0001 . Conclusions The multimodal treatment was more effective and TENS alone or in association presented longer lasting results for improvement of clinical symptoms of OAB and Aims : This study compared the effectiveness of solifenacin succinate ( SS ) versus percutaneous tibial nerve stimulation ( PTNS ) in women with overactive bladder syndrome ( OABS ) . Methods : A r and omized controlled crossover study of 40 women with OABS was performed . Patients were r and omized into two groups . In group A , patients received SS and then PTNS . In group B , patients underwent PTNS and then SS . Voiding diaries , quality of life surveys and patient perception of intensity of urgency question naire were performed before and after each treatment . The global impression of improvement question naire was performed at the end of the study . Results : A reduction in the number of daily micturitions , episodes of nocturia and urge incontinence were found with both SS and PTNS in all groups , but PTNS showed a greater effectiveness than SS . There was an increase in voided volume in all groups with both SS and PTNS , but patients treated with PTNS had a greater increase . PTNS showed greater effectiveness in patient perception of urgency and quality of life . Conclusion : This study demonstrates the effectiveness of SS and PTNS In women with overactive bladder symptoms . However , greater improvements were found with PTNS OBJECTIVE In sacral as well as tibial nerve stimulation test stimulation is the main prognostic factor for success . In our study we tried to identify prognostic patient characteristics to improve patient selection for neuromodulation therapy . METHODS PTNS was applied to 132 patients in 8 study centers ( 51 men , 81 women , mean age of 53 years ( range : 21 - 82 ) ) . 83 patients were treated for overactive bladder , 16 for non-obstructive urinary retention and 33 for chronic pelvic pain . All patients had to fill out micturition or pain diaries , as well as quality of life question naires before and after treatment . Patient characteristics were evaluated for their prognostic value for successful outcome of neuromodulation therapy with use of logistic regression . RESULTS Objective success was seen in 32.6 % of patients , subjective success in 51.5 % . Most evaluated clinical parameters proved not to be of prognostic value . A history of sexual and /or physical abuse was found in 12 of 103 interviewed patients , but did not alter PTNS treatment outcome . However , a low total score at baseline in the SF-36 question naire proved to be predictive for not obtaining objective ( OR 0.444 [ 95 % CI : 0.198 - 0.996 ] , p = 0.04 ) or subjective success ( OR 0.424 [ CI : 0.203 - 0.887 ] , p = 0.02 ) . Especially patients with a low SF-36 Mental Component Summary were prone to fail neuromodulation therapy : OR 0.123 ( 95 % CI : 0.273 - 0.552 ) , p = 0.006 for objective success . These patients also scored worse on disease-specific quality of life question naires , although they had no different disease severity compared to patients with good mental health . CONCLUSION Bad mental health as measured with the SF-36 Mental Component Summary does not depend on symptom severity and is a negative predictive factor for success of percutaneous tibial nerve stimulation . It therefore might be used as a tool for better patient selection in neuromodulation therapy Objective To perform Stoller afferent neurostimulation ( SANS ) with and without a low-dose anticholinergic ( oxybutynin hydrochloride ) in patients with detrusor overactivity and compare the results obtained with the two therapeutic approaches . Material and methods A total of 43 patients with symptoms of detrusor overactivity ( frequency , urgency , urge incontinence ) underwent urodynamic studies ( UDS ) . Those in whom UDS revealed phasic detrusor overactivity were evaluated using a quality of life question naire and voiding diaries . Patients were r and omized into two groups : Group 1 received SANS alone ; Group 2 received SANS combined with a low-dose anticholinergic ( 5 mg of oral oxybutynin hydrochloride ) . Both groups were re-evaluated following 8 weeks of therapy . Results There were 21 patients in Group 1 and 22 in Group 2 . The treatment response rate was 61.6 % and 83.2 % in Groups 1 and 2 , respectively . In both groups , the best symptomatic improvements were obtained in patients with urge incontinence . The percentage decreases in the mean number of symptoms of frequency and urgency were 36.7 % and 46.1 % , respectively in Group 1 and 44.2 % and 61.1 % , respectively in Group 2 . However , there were no statistically significant differences in the effects on frequency and urgency between the two groups . The anticholinergic drug was well tolerated by all patients in Group 2 . One patient reported local tenderness , and a small hematoma developed in another following SANS therapy . Conclusion SANS is an easy and inexpensive therapeutic method with low morbidity in patients with an overactive bladder . Combination with a low-dose anticholinergic increases the success rate without causing any significant side-effects AIMS To evaluate the safety , sustained effectiveness , and treatment interval for percutaneous tibial nerve stimulation ( PTNS ) for overactive bladder ( OAB ) therapy through 24 months . METHODS A prospect i ve study following treatment success after 12 weekly PTNS treatments , subjects were prescribed a 14-week tapering protocol , followed by ongoing therapy with a Personal Treatment Plan determined by the investigator and subject to sustain subject OAB symptom improvement . Question naires were completed every 3 months , voiding diaries every 6 months ; adverse events were reported throughout . RESULTS Of 50 subjects enrolled , 35 remained in the study at 24 months . During the 24 months following initial treatment success and a 14-week tapering protocol , mean treatments per month was 1.3 . Voiding diary and OAB-q data demonstrate sustained improvement reported at 13 weeks through 24 months . Improvements in frequency , urge incontinence episodes , night-time voids and moderate-to-severe urgency episodes from voiding diaries at 6 , 12 , 18 , and 24 months were statistically significant compared to baseline ( prior to initial 12 weekly treatments ) . Compared to baseline , OAB-q symptom severity scores and health related quality of life scores were statistically significant for improvement at each tested time point . Five mild adverse events of unknown relation to treatment were reported . CONCLUSION Sustained safety and efficacy of PTNS were demonstrated over 24 months with initial success after 12 weekly treatments , followed by a 14-week prescribed tapering protocol and a Personalized Treatment Plan . With an average of 1.3 treatments per month , PTNS therapy is a safe , durable , and valuable long-term OAB treatment option to sustain clinical ly significant OAB symptom control To determine the effect of a pause in percutaneous tibial nerve stimulation ( PTNS ) in successfully treated patients with an overactive bladder ( OAB ) , and the reproducibility of successful treatment when restored PURPOSE The Overactive Bladder Innovative Therapy trial was a r and omized , multicenter , controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine . The reduction in overactive bladder symptoms along with global response assessment s was evaluated . MATERIAL S AND METHODS A total of 100 adults with urinary frequency were r and omized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine . Voiding diaries and an overactive bladder question naire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency , urinary urge incontinence episodes , voids causing waking , volume voided , urgency episodes and quality of life indices . Global response assessment s were completed by subjects and investigators after 12 weeks of therapy . RESULTS The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5 % reporting cure or improvement compared to 54.8 % of subjects on tolterodine ( p = 0.01 ) . Assessment s by investigators were similar but did not reach statistical significance ( p = 0.05 ) . After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency , urge urinary incontinence episodes , urge severity and nighttime voids , as well as for improvement in voided volume . There were no serious adverse events or device malfunctions . CONCLUSIONS This multicenter , r and omized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms , and with objective effectiveness comparable to that of pharmacotherapy . Percutaneous tibial nerve stimulation may be considered a clinical ly significant alternative therapy for overactive bladder AIM Aim of our study was to compare the results of posterior tibial nerve stimulation ( PTNS ) performed weekly with those of PTNS performed 3 times per week in patients with overactive bladder syndrome . METHODS Thirty-five patients ( 28 females , 7 males ) with overactive bladder syndrome not responding to antimuscarinic therapy were enrolled in a prospect i ve study . A total of 17 out of 35 patients were r and omly assigned to group A and treated with a PTNS protocol based on weekly stimulation sessions ; 18 out of 35 patients were r and omly assigned to group B and treated with a PTNS protocol based on stimulation sessions performed 3 times per week . All subjects were evaluated by means of 24 h bladder diaries , quality of life question naires ( I-QoL , SF36 ) and urodynamic evaluation before and after treatment . Patients were asked after each stimulation session to give their opinion on the efficacy of the treatment . We have considered ' ' success ' ' those patients who presented a reduction > 50 % of the micturition episodes/24 h ( ME/24 ) or ( if incontinent ) of the incontinence episodes/24 h ( IE/24 ) . Results before and after treatments in both groups were collected and statistically compared . RESULTS As a whole , 11/17 patients ( 63 % ) in group A and 12/18 patients ( 67 % ) in group B were considered ' ' success ' ' ; 4/11 ( 36 % ) incontinent patients in group A and 5/11 ( 45 % ) incontinent patients in group B were completely cured after treatment . In both groups , patients reported subjective improvement after 6 - 8 stimulation sessions . CONCLUSIONS Our findings seem to show that the periodicity of stimulation does not effect the results of PTNS treatment . The advantage of more frequent stimulation sessions is to achieve earlier a clinical improvement Aim : In this prospect i ve observational study , we investigated the efficacy of Stoller afferent nerve stimulation ( SANS ) in subjects with overactive bladder who failed anticholinergic treatment . Methods : Thirty-five subjects with overactive bladder who failed therapy with oxybutynin participated in this study . Treatment ( n=35 ) was given once a week for 30 minutes for overall 10 weeks . In treatment , SANS device ( Urosurge ® ) was used . Subjects were assessed with 3-day voiding diary , SEAPI quality of life question naires and cystometry before therapy after completion of therapy and at one-year follow-up . Results : In 54 % ( n=19 ) of subjects complete recovery was obtained after treatment . Urgency and SEAPI were reduced significantly whereas urine volume increased significantly ( p<0.01 ) . Complete recovery was maintained in eight of the 19 subjects at one year . Conclusions : SANS treatment has a short-term positive effect in patients with resistant overactive bladder . However , it was also established that efficacy was maintained at 1 year in only 23 % of subjects Objective . Anti-muscarinic treatment alone and peripheral neuromodulation with concomitant anti-muscarinic treatment were compared in patients with severe overactive bladder . Methods . In this prospect i ve study , 40 women with severe overactive bladder according to the 7-day voiding diary without any prior treatment completed the Incontinence Impact Question naire ( IIQ-7 ) and were r and omised into anti-muscarinic-alone and combination treatment groups . Twenty women received daily 4 mgs of tolterodine orally and in 20 women Stoller afferent neuro-stimulation ( SANS ) therapy was performed concomitantly for 12 weeks to the same anti-muscarinic regimen . After 12 weeks of therapy , two of the patients drop out of the study and remaining patients filled out the IIQ-7 question naire and the 7-day voiding diary again . Pretreatment and post-treatment QoL scores and the 7-day voiding diaries were compared . Mann – Whitney U , Wilcoxon and two sided significance tests were used . Results . Thirty-eight women fulfilling the criteria were included in the study . Severity of overactive bladder symptoms decreased significantly in both treatment groups . However , the decrease in combination treatment group was more significant than the anti-muscarinic-alone group . Adverse events were similar between the two groups . Conclusion . Combining SANS and anti-muscarinic therapy result ed in significantly better clinical outcomes and IIQ-7 scores as compared with anti-muscarinic treatment alone in patients with severe overactive bladder PURPOSE The Study of Urgent PC vs Sham Effectiveness in Treatment of Overactive Bladder Symptoms ( SUmiT ) was a multicenter , double-blind , r and omized , controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy . The improvement in global response assessment , voiding diary parameters , and overactive bladder and quality of life question naires was evaluated . MATERIAL S AND METHODS A total of 220 adults with overactive bladder symptoms were r and omized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or sham therapy . Overactive bladder and quality of life question naires as well as 3-day voiding diaries were completed at baseline and at 13 weeks . Subject global response assessment s were completed at week 13 . RESULTS The 13-week subject global response assessment for overall bladder symptoms demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5 % reporting moderately or markedly improved responses compared to 20.9 % of sham subjects from baseline ( p < 0.001 ) . All individual global response assessment subset symptom components demonstrated statistically significant improvement from baseline to 13 weeks for percutaneous tibial nerve stimulation compared to sham . Voiding diary parameters after 12 weeks of therapy showed percutaneous tibial nerve stimulation subjects had statistically significant improvements in frequency , nighttime voids , voids with moderate to severe urgency and urinary urge incontinence episodes compared to sham . No serious device related adverse events or malfunctions were reported . CONCLUSIONS This pivotal multicenter , double-blind , r and omized , sham controlled trial provides level I evidence that percutaneous tibial nerve stimulation therapy is safe and effective in treating overactive bladder symptoms . The compelling efficacy of percutaneous tibial nerve stimulation demonstrated in this trial is consistent with other recently published reports and supports the use of peripheral neuromodulation therapy for overactive bladder PURPOSE This is a prospect i ve , double-blind , placebo controlled study , based on an original placebo technique , performed to evaluate the efficacy of percutaneous tibial nerve stimulation in female patients with detrusor overactivity incontinence . MATERIAL S AND METHODS A total of 35 female patients presenting with detrusor overactivity incontinence that did not respond to antimuscarinic therapy were r and omly assigned to percutaneous tibial nerve stimulation or to a control group . The percutaneous tibial nerve stimulation group ( 18 patients ) was treated with 12 percutaneous tibial nerve stimulation sessions . The control group ( 17 patients ) received an original placebo treatment using a 34 gauge needle placed in the medial part of the gastrocnemius muscle . The sessions lasted for 30 minutes and were performed 3 times weekly as percutaneous tibial nerve stimulation sessions . All patients were evaluated with bladder diaries as well as quality of life scores before and after treatment . Patients showing a reduction in urge incontinence episodes greater than 50 % were considered responders . RESULTS Some patients ( 1 in the percutaneous tibial nerve stimulation group and 2 in the placebo group ) did not complete the study for reasons not related to the technique . Of 17 patients in the percutaneous tibial nerve stimulation group 12 ( 71 % ) and of 15 in placebo group 0 were considered responders according to the previously reported definition ( p < 0.001 ) . Improvement in the number of incontinence episodes , number of voids , voided volume and incontinence quality of life score were statistically significant in the percutaneous tibial nerve stimulation group but not in the placebo group . CONCLUSIONS Percutaneous tibial nerve stimulation can be considered an effective treatment for detrusor overactivity incontinence with 71 % of patients considered responders , while none of those treated with placebo was considered a responder . The relevance of a placebo effect seems to be negligible in this patient population |
11,159 | 26,165,367 | The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions : depressive symptoms ( compared to anti-depressants and placebo ) , premenstrual symptoms , and sexual dysfunction .
In addition , saffron use was also effective in reducing excessive snacking behavior .
CONCLUSION Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression , premenstrual syndrome , sexual dysfunction and infertility , and excessive snacking behaviors . | BACKGROUND Throughout the past three decades , increased scientific attention has been given to examining saffron 's ( Crocus sativus L. ) use as a potential therapeutic or preventive agent for a number of health conditions , including cancer , cardiovascular disease , and depression .
OBJECTIVE The purpose of this systematic review is to examine and categorize the current state of scientific evidence from r and omized controlled trials ( RCTs ) regarding the efficacy of saffron on psychological/behavioral outcomes . | Snacking is an uncontrolled eating behavior , predisposing weight gain and obesity . It primarily affects the female population and is frequently associated with stress . We hypothesized that oral supplementation with Satiereal ( Inoreal Ltd , Plerin , France ) , a novel extract of saffron stigma , may reduce snacking and enhance satiety through its suggested mood-improving effect , and thus contribute to weight loss . Healthy , mildly overweight women ( N = 60 ) participated in this r and omized , placebo-controlled , double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period . Snacking frequency , the main secondary variable , was assessed by daily self-recording of episodes by the subjects in a nutrition diary . Twice a day , enrolled subjects consumed 1 capsule of Satiereal ( 176.5 mg extract per day ( n = 31 ) or a matching placebo ( n = 29 ) . Caloric intake was left unrestricted during the study . At baseline , both groups were homogeneous for age , body weight , and snacking frequency . Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks ( P < .01 ) . The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group ( P < .05 ) . Other anthropometric dimensions and vital signs remained almost unchanged in both groups . No subject withdrawal attributable to a product effect was reported throughout the trial , suggesting a good tolerability to Satiereal . Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss . The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective Objectives . In a previous r and omized clinical trial ( Falsini et al. ( 2010 ) ) , it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration ( AMD ) . The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration . Design . Longitudinal , interventional open-label study . Setting . Outpatient ophthalmology setting . Participants . Twenty-nine early AMD patients ( age range : 55–85 years ) with a baseline visual acuity > 0.3 . Intervention . Saffron oral supplementation ( 20 mg/day ) over an average period of treatment of 14 ( ±2 ) months . Measurements . Clinical examination and focal-electroretinogram-(fERG- ) derived macular ( 18 ° ) flicker sensitivity estimate ( Falsini et al. ( 2010 ) ) every three months over a followup of 14 ( ±2 ) months . Retinal sensitivity , the reciprocal value of the estimated fERG amplitude threshold , was the main outcome measure . Results . After three months of supplementation , mean fERG sensitivity improved by 0.3 log units compared to baseline values ( P < 0.01 ) , and mean visual acuity improved by two Snellen lines compared to baseline values ( 0.75 to 0.9 , P < 0.01 ) . These changes remained stable over the follow-up period . Conclusion . These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup Background The morbidity and mortality associated with depression are considerable and continue to increase . Depression currently ranks fourth among the major causes of disability worldwide , after lower respiratory infections , prenatal conditions , and HIV/AIDS . Crocus sativus L. is used to treat depression . Many medicinal plants textbooks refer to this indication whereas there is no evidence -based document . Our objective was to compare the efficacy of stigmas of Crocus sativus ( saffron ) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind r and omized trial . Methods Thirty adult out patients who met the Diagnostic and Statistical Manual of Mental Disorders , 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial . Patients have a baseline Hamilton Rating Scale for Depression score of at least 18 . In this double-blind , single-center trial , patients were r and omly assigned to receive capsule of saffron 30 mg/day ( TDS ) ( Group 1 ) and capsule of imipramine 100 mg/day ( TDS ) ( Group 2 ) for a 6-week study . Results Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression ( F = 2.91 , d.f . = 1 , P = 0.09 ) . In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable . Conclusion The main overall finding from this study is that saffron may be of therapeutic benefit in the treatment of mild to moderate depression . To the best of our knowledge this is the first clinical trial that supports this indication for saffron . A large-scale trial with placebo control is warranted Our objective was to examine the effect of an Iranian herbal drug in the treatment of primary dysmenorrhea . A r and omized , double-blind , placebo-controlled pilot trial among 180 female students at Isfahan University dormitory aged 18 to 27 who suffered from primary dysmenorrhea was undertaken . The participants were r and omly divided into three groups : herbal drug , mefenamic acid , and placebo . The herbal drug group was given 500 mg of highly purified saffron , celery seed , and anise ( SCA ) extracts three times a day for three days , starting from the onset of bleeding or pain . Participants were followed for two to three cycles from the beginning of menstruation through the three days of bleeding . Main outcome measures were the severity and duration of pain at 2 and 3 months . A visual analogue scale was used to record pain . There were statistically significant reductions in pain scores and pain duration scores in the groups that took SCA ( P < . 001 ) and mefenamic acid ( P < . 01 ) . The decrease in pain score was reflected by a significant reduction in other drug use among the treatment groups compared with the women in the placebo group . The magnitude of the reduction was significantly greater in the SCA group than in the mefenamic acid and placebo groups . Both drugs effectively relieved menstrual pain as compared with the placebo . More clinical trials are needed to establish the efficacy of this herbal drug Depressive disorders are very common in clinical practice , with approximately 11.3 of all adults afflicted during any a year . Saffron is the world 's most expensive spice and apart from its traditional value as a food additive , recent studies indicate several therapeutic effects for saffron . It is used for depression in Persian traditional medicine . Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus ( stigma ) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind , r and omized trial . Forty adult out patients who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial . In this double-blind , single-center trial and r and omized trial , patients were r and omly assigned to receive capsules of saffron 30 mg/day ( BD ) ( Group 1 ) and capsule of fluoxetine 20 mg/day ( BD ) ( Group 2 ) for a 6-week study . Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression ( F = 0.13 , d.f . = 1 , P = 0.71 ) . There were no significant differences in the two groups in terms of observed side effects . The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression . A large-scale trial is justified Depression is one of the most common neuropsychiatric conditions , with a lifetime prevalence approaching 17 % . Although a variety of pharmaceutical agents is available for the treatment of depression , psychiatrists find that many patients can not tolerate the side effects , do not respond adequately , or finally lose their response . On the other h and , many herbs with psychotropic effects have far fewer side effects . They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants . A number of recent pre clinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect . Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed out patients in an 8-week pilot double-blind r and omized trial . Forty adult out patients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial . Patients have a baseline Hamilton Rating Scale for Depression score of at least 18 . In this double-blind and r and omized trial , patients were r and omly assigned to receive capsule of petal of C. sativus 15 mg bid ( morning and evening ) ( Group 1 ) and fluoxetine 10 mg bid ( morning and evening ) ( Group 2 ) for a 8-week study . At the end of trial , petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression ( F=0.03 , d.f.=1 , P=0.84 ) . In addition , in the both treatments , the remission rate was 25 % . There were no significant differences in the two groups in terms of observed side effects . The present study is supportive of other studies which show antidepressant effect of C. sativus Background To determine whether the functional effects of oral supplementation with Saffron , a natural compound that proved to be neuroprotective in early age-related macular degeneration , are influenced by complement factor H ( CFH ) and age-related maculopathy susceptibility 2 ( ARMS2 ) risk genotypes . Methods Thirty-three early AMD patients , screened for CFH ( rs1061170 ) and ARMS2 ( rs10490924 ) polymorphisms and receiving Saffron oral supplementation ( 20 mg/day ) over an average period of treatment of 11 months ( range , 6–12 ) , were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular ( 18 ° ) flicker sensitivity estimate . fERG amplitude and macular sensitivity , the reciprocal value of the estimated fERG amplitude threshold , were the main outcome measures . Results After three months of supplementation , mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values ( p < 0.01 ) . These changes were stable throughout the follow-up period . No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes . Conclusions The present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease Rationale Saffron ( Crocus sativus L. ) has shown aphrodisiac effects in some animal and human studies . Objectives To assess the efficacy and tolerability of saffron in fluoxetine-related sexual dysfunction . Methods This was a 4-week r and omized double-blind placebo-controlled study . Thirty-six married male patients with major depressive disorder whose depressive symptoms had been stabilized on fluoxetine and had subjective complaints of sexual impairment entered the study . The patients were r and omly assigned to saffron ( 15 mg twice per day ) or placebo for 4 weeks . International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4 . Results Thirty patients finished the study . Baseline characteristics as well as baseline and final depressive symptoms scores were similar between the two groups . Effect of time × treatment interaction on the total score was significant [ Greenhouse – Geisser-corrected , F ( 1.444 , 40.434 ) = 6.154 , P = 0.009 ] . By week 4 , saffron result ed in significantly greater improvement in erectile function ( P < 0.001 ) and intercourse satisfaction domains ( P = 0.001 ) , and total scores ( P < 0.001 ) than the placebo group . Effect of saffron did not differ significantly from that of placebo in orgasmic function ( P = 0.095 ) , overall satisfaction ( P = 0.334 ) , and sexual desire ( P = 0.517 ) domains scores . Nine patients ( 60 % ) in the saffron group and one patient ( 7 % ) in the placebo group achieved normal erectile function ( score > 25 on erectile function domain ) at the end of the study ( P value of Fisher ’s exact test = 0.005 ) . Frequency of side effects were similar between the two groups . Conclusions Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction INTRODUCTION We conducted this study to determine the effects of saffron ( Crocus sativus ) on the results of semen analysis in men with idiopathic infertility . MATERIAL S AND METHODS In this clinical trial , 52 nonsmoker infertile men whose problem could not be solved surgically were enrolled . They were treated by saffron for 3 months . Saffron , 50 mg , was solved in drinking milk and administered 3 times a week during the study course . Semen analysis was done before and after the treatment and the results were compared . RESULTS The mean percentage of sperm with normal morphology was 26.50 + /- 6.44 % before the treatment which increased to 33.90 + /- 10.45 % , thereafter ( P < .001 ) . The mean percentage of sperm with Class A motility was 5.32 + /- 4.57 % before and 11.77 + /- 6.07 % after the treatment ( P < .001 ) . Class B and C motilities were initially 10.09 + /- 4.20 % and 19.79 + /- 9.11 % which increased to 17.92 + /- 6.50 % ( P < .001 ) and 25.35 + /- 10.22 % ( P < .001 ) , respectively . No significant increase was detected in sperm count ; the mean sperm count was 43.45 + /- 31.29 x 106/mL at baseline and 44.92 + /- 28.36x 106/mL after the treatment period ( P = .30 ) . CONCLUSION Saffron , as an antioxidant , is positively effective on sperm morphology and motility in infertile men , while it does not increase sperm count . We believe further studies on larger sample sizes are needed to eluci date the potential role and mechanism of action of saffron and its ingredient in the treatment of male infertility Saffron ( Crocus sativus ) stigma tablets were evaluated for short-term safety and tolerability in healthy adult volunteers . The study was a double-blind , placebo-controlled design consisting of a 1 week treatment of saffron tablets . Volunteers were divided into 3 groups of 10 each ( 5 males and 5 females ) . Group I received placebo ; groups 2 and 3 received 200 and 400 mg saffron tablets , respectively , for 7 days . General measures of health were recorded during the study such as hematological , biochemical and electrocardiographic parameters done in pre- and post-treatment periods . Clinical examination showed no gross changes in all volunteers after intervention . Saffron with higher dose ( 400 mg ) decreased st and ing systolic blood pressure and mean arterial pressures significantly . Saffron decreased slightly some hematological parameters such as red blood cells , hemoglobin , hematocrit and platelets . Saffron increased sodium , blood urea nitrogen and creatinine . This study showed that saffron tablets may change some hematological and biochemical parameters . However , these alterations were in normal ranges and they were not important clinical ly 50 mg of Saffron dissolved in 100 ml of milk was administered twice a day to 20 human subjects . Lipoprotein oxidation susceptibility ( LOS ) was estimated initially and after 3 and 6 weeks . There was a constant decrease in LOS during this period . From a mean of 66.4 + /- 3.18 it decreased to 38.3 + /- 2.8 in 10 healthy individuals and from 76.0 + /- 3.72 to 48.8 + /- 3.0 in 10 patients of CAD . The significant fall ( P < 0.001 ) in LOS indicates the potential of Saffron as an antioxidant Rationale There is increasing evidence to suggest the possible efficacy of Crocus sativus ( saffron ) in the management of Alzheimer ’s disease ( AD ) . Objective The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD . Methods Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week , double-blind study of parallel groups of patients with AD . The main efficacy measures were the change in the Alzheimer ’s Disease Assessment Scale — cognitive subscale and Clinical Dementia Rating Scale — Sums of Boxes scores compared with baseline . Adverse events ( AEs ) were systematic ally recorded . Participants were r and omly assigned to receive a capsule saffron 30 mg/day ( 15 mg twice per day ) or donepezil 10 mg/day ( 5 mg twice per day ) . Results Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks . The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting , which occurred significantly more frequently in the donepezil group . Conclusion This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer ’s disease . This trial is registered with the Iranian Clinical Trials Registry ( I RCT 138711051556N1 ) Saffron ( Crocus sativus Linn . ) have been perceived by the public as a strong aphrodisiac herbal product . However , studies addressing the potential beneficial effects of saffron on erectile function ( EF ) in men with ED are lacking . Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED . After a 4-week baseline assessment , 346 men with ED ( mean age 46.6±8.4 years ) were r and omized to receive on-dem and sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa , separated by a 2-week washout period . To determine the type of ED , penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 μg prostagl and in E1 , pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed . Subjects were assessed with an International Index of Erectile Function ( IIEF ) question naire , Sexual Encounter Profile ( SEP ) diary questions , patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ) question naire and the Global Efficacy Question ( GEQ ) ‘ Has the medication you have been taking improved your erections ? ’ No significant improvements were observed with regard to the IIEF sexual function domains , SEP questions and EDITS scores with saffron administration . The mean changes from baseline values in IIEF-EF domain were + 87.6 % and + 9.8 % in sildenafil and placebo groups , respectively ( P=0.08 ) . We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron . Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients ( 72.4 vs 25.4 , P=0.001 ) . Mean per patient ‘ yes ’ responses to GEQ was 91.2 and 4.2 % for sildenafil and saffron , respectively ( P=0.0001 ) . These findings do not support a beneficial effect of saffron administration in men with ED OBJECTIVE Saffron ( Crocus sativus L. ) has shown beneficial aphrodisiac effects in some animal and human studies . The aim of the present study was to assess the safety and efficacy of saffron on selective serotonin reuptake inhibitor-induced sexual dysfunction in women . METHODS This was a r and omized double-blind placebo-controlled study . Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study . The patients were r and omly assigned to saffron ( 30 mg/daily ) or placebo for 4 weeks . Measurement was performed at baseline , week 2 , and week 4 using the Female Sexual Function Index ( FSFI ) . Side effects were systematic ally recorded . RESULTS Thirty-four women had at least one post-baseline measurement and completed the study . Two-factor repeated measure analysis of variance showed significant effect of time × treatment interaction [ Greenhouse-Geisser 's corrected : F(1.580 , 50.567 ) = 5.366 , p = 0.012 ] and treatment for FSFI total score [ F(1 , 32 ) = 4.243 , p = 0.048 ] . At the end of the fourth week , patients in the saffron group had experienced significantly more improvement in total FSFI ( p < 0.001 ) , arousal ( p = 0.028 ) , lubrication ( p = 0.035 ) , and pain ( p = 0.016 ) domains of FSFI but not in desire ( p = 0.196 ) , satisfaction ( p = 0.206 ) , and orgasm ( p = 0.354 ) domains . Frequency of side effects was similar between the two groups . CONCLUSIONS It seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal , lubrication , and pain Depression is a major worldwide health problem . Indeed , by 2020 , depressive disorders are estimated to represent the second largest disease burden worldwide . Although a variety of pharmaceutical agents are available for the treatment of depression , psychiatrists find that many patients can not tolerate the side effects , do not respond adequately , or finally lose their response . Our objective was to assess the efficacy of petal of Crocus sativus in the treatment of mild-to-moderate depression in a 6-week double-blind , placebo-controlled and r and omized trial . Forty adult out patients who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition for major depression based on the structured clinical interview for DSM IV participated in the trial . In this double-blind , placebo-controlled and r and omized trial , patients were r and omly assigned to receive capsule of petal of C. sativus 30 mg/day ( BD ) ( Group 1 ) and capsule of placebo ( BD ) ( Group 2 ) for a 6-week study . At 6 weeks , petal of C. sativus produced a significantly better outcome on Hamilton Depression Rating Scale than placebo ( d.f.=1 , F=16.87 , p<0.001 ) . There were no significant differences in the two groups in terms of observed side effects . The results of this study indicate the efficacy of petal of C. sativus in the treatment of mild-to-moderate depression . A large-scale trial is justified OBJECTIVE A significant correlation exists between coronary artery diseases and depression . The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention ( PCI ) . METHODS In this r and omized double-blind parallel-group study , 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were r and omized to receive either fluoexetine ( 40mg/day ) or saffron ( 30mg/day ) capsule for six weeks . Participants were evaluated by Hamilton depression rating scale ( HDRS ) at weeks 3 and 6 and the adverse events were systemically recorded . RESULTS By the study endpoint , no significant difference was detected between two groups in reduction of HDRS scores ( P=0.62 ) . Remission and response rates were not significantly different as well ( P=1.00 and P=0.67 ; respectively ) . There was no significant difference between two groups in the frequency of adverse events during this trial . LIMITATIONS Relatively small sample size and short observational period were the major limitations of this study . CONCLUSION Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression Depression is a serious disorder in today 's society , with estimates of lifetime prevalence as high as 21 % of the general population in some developed countries . As a therapeutic plant , saffron is considered excellent for stomach ailments and as an antispasmodic , to help digestion and to increase appetite . It is also used for depression in Persian traditional medicine . Our objective was to assess the efficacy of the stigmas of Crocus sativus ( saffron ) in the treatment of mild to moderate depression in a 6-week double-blind , placebo-controlled and r and omized trial . Forty adult out patients who met the Diagnostic and Statistical Manual of Mental Disorders , 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial . Patients had a baseline Hamilton rating scale for depression score of at least 18 . In this double-blind , placebo-controlled , single-centre and r and omized trial , patients were r and omly assigned to receive a capsule of saffron 30 mg[sol ] day ( BD ) ( Group 1 ) or a capsule of placebo ( BD ) ( Group 2 ) for a 6-week study . At 6 weeks , Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo ( d.f . = 1 , F = 18.89 , p < 0.001 ) . There were no significant differences in the two groups in terms of the observed side effects . The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression . A large-scale trial is justified Saffron is the dried stigmata of the flowers of saffron ( Crocus sativus L. ) . Saffron is rich in carotenoids and carotenoids affect immunity . Thus , in this r and omized double-blind placebo-controlled clinical trial with healthy men aged 21.4 ± 0.8 years ( mean ± SE ) , the effects of taking one 100 mg saffron tablet daily for 6 weeks on the blood serum levels of IgG , IgM , IgA , C(3 ) and C(4 ) complements , counts and percentages of white blood cells , platelets , neutrophils , eosinophils , basophils , lymphocytes and monocytes , levels of some hematological parameters and levels of creatinine , SGOT and SGPT were evaluated in 45 subjects and compared with the placebo group ( n = 44 ) . After 3 weeks , saffron increased the IgG level and decreased the IgM level compared with the baseline and placebo ( p < 0.01 ) , decreased the percentage of basophils and the count of platelets compared with baseline , but increased the percentage of monocytes compared with placebo ( p < 0.05 ) . However , these parameters returned to the baseline levels after 6 weeks . Saffron did not have any significant effects on the other parameters . No adverse effects were reported . The results suggest that the sub-chronic daily use of 100 mg saffron has temporary immunomodulatory activities without any adverse effects WHAT IS KNOWN Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response . Crocus sativus ( saffron ) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer 's disease ( AD ) . OBJECTIVE The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD . METHODS Forty-six patients with probable AD were screened for a 16-week , double-blind study of parallel groups of patients with mild to moderate AD . The psychometric measures , which included AD assessment scale-cognitive subscale ( ADAS-cog ) , and clinical dementia rating scale-sums of boxes , were performed to monitor the global cognitive and clinical profiles of the patients . Patients were r and omly assigned to receive capsule saffron 30 mg/day ( 15 mg twice per day ) ( Group A ) or capsule placebo ( two capsules per day ) for a 16-week study . RESULTS After 16 weeks , saffron produced a significantly better outcome on cognitive function than placebo ( ADAS-cog : F=4·12 , d.f.=1 , P=0·04 ; CDR : F=4·12 , d.f.=1 , P=0·04 ) . There were no significant differences in the two groups in terms of observed adverse events . WHAT IS NEW AND CONCLUSION This double-blind , placebo-controlled study suggests that at least in the short-term , saffron is both safe and effective in mild to moderate AD . Larger confirmatory r and omized controlled trials are called for PURPOSE To evaluate the functional effect of short-term supplementation of saffron , a spice containing the antioxidant carotenoids crocin and crocetin , in early age-related macular degeneration ( AMD ) . METHODS Twenty-five patients with AMD were r and omly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months . Focal electroretinograms ( fERGs ) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation . fERGs were recorded in response to a sinusoidally modulated ( 41 Hz ) , uniform field presented to the macular region ( 18 ° ) at different modulations between 16.5 % and 93.5 % . Main outcome measures were fERG amplitude ( in microvolts ) , phase ( in degrees ) , and modulation thresholds . RESULTS After saffron , patients ' fERGs were increased in amplitude , compared with either baseline or values found after placebo supplementation ( mean change after saffron , 0.25 log μV ; mean change after placebo , -0.003 log μV ; P < 0.01 ) . fERG thresholds were decreased after saffron supplementation but not placebo , compared with baseline ( mean change after saffron , -0.26 log units ; mean change after placebo , 0.0003 log units ) . CONCLUSIONS The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD . Although the results must be further replicated and the clinical significance is yet to be evaluated , they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways , possibly beyond their antioxidant properties . ( Clinical Trials.gov number , NCT00951288 . ) |
11,160 | 27,776,086 | Clinical examination is most often sufficient to diagnose plagiocephaly ( quality , Class III ; strength , Level III ) .
Within the limits of this systematic review , the evidence suggests that imaging is rarely necessary and should be reserved for cases in which the clinical examination is equivocal .
When needed , 3-dimensional cranial topographical photo , skull x-rays , or ultrasound imaging is almost always sufficient for definitive diagnosis .
Computed tomography scanning should not be used to diagnose plagiocephaly , but it may be necessary to rule out craniosynostosis . | BACKGROUND No evidence -based guidelines exist for the imaging of patients with positional plagiocephaly .
OBJECTIVE The objective of this systematic review and evidence -based guideline is to answer the question , Is imaging necessary for infants with positional plagiocephaly to make a diagnosis ? | Objective We defined parameters that could differentiate between positional and synostotic plagiocephaly and defined a diagnostic chart for decision making . Design Prospect i ve study . Setting We examined 411 children with non-syndromic skull abnormalities between January 2011 and December 2012 . Participants A total of 8 infants under 1 year of age with proven unilateral non-syndromic lambdoid synostosis ( LS ) and 261 children with positional deformity were examined to outline the specific clinical features of both diagnoses . After clinical examination , an ultrasound revealed either a closed suture suggestive of LS or a patent lambdoid suture suggestive of positional deformity . For patients with synostosis , plain radiographs , MR imaging and follow-up examinations were performed . In cases of open sutures , only follow-ups were completed . Main outcome measure Clinical , imaging , genesis and treatment differences between positional plagiocephaly and LS . Results In all 8 cases of unilateral LS and 258 cases of positional plagiocephaly , the diagnosis was established by clinical examination alone . In three cases of positional plagiocephaly , diagnosis was determined after an additional ultrasonography . MR imaging revealed a unilateral tonsillar herniation in five of the eight children with LS and hydrocephalus in one child . Conclusions We have suggested a list of clinical features that specify the underlying cause of posterior plagiocephaly . An additional ultrasound scanning confirmed the diagnosis without any risks of ionising radiation or sedation as in a CT scan Deformational plagiocephaly , cranial asymmetry secondary to positioning , continues to be a leading cause of head shape abnormalities in infants . Treatment recommendations include nonintervention , positioning therapies , and helmet therapy . Although most agree that surgical intervention is rarely indicated , the ideal therapy is not agreed on . Some even debate the necessity of treatment , especially third-party payers . The purpose of this prospect i ve study is to use an objective outcome analysis tool , computerized tomography , to assess the efficacy of a soft shell helmet therapy . Sixty-nine children with a diagnosis of deformational plagiocephaly were enrolled in this study to assess the success of a soft shell helmet for the correction of cranial asymmetry . Computed tomography scanning was done before therapy and 6 months after the initiation of therapy . Three-dimensional reconstructions of these scans were reformatted into a st and ardized orientation by utilizing the nasion ( radix ) , frontozygomatic suture lines , and posterior aspect of the foramen magnum . Intracranial volumes were calculated on a quadrant basis , and asymmetry was evaluated with regard to the hemispheres ( left versus right ) and the posterior quadrants . Thirty-four children ( 27 boys and 7 girls ) completed the study protocol . The side involved was the right in 62 % of cases and the left in 38 % . Mean age at the initial scan was 6.3 months , and mean age at the follow-up scan was 14 months . Mean duration of helmet therapy was 7 months . Compliance with therapy was average to above average in 88 % of the children and poor in 12 % . There was a 36 % to 54 % improvement in asymmetry in the compliant patients over the 6-month study period . Soft shell helmet therapy is an effective technique to decrease cranial asymmetry based on objective outcome measurements . Additionally , it is cost-effective , with the total cost of therapy for the helmet and office visits ranging from $ 600 to $ 700 . This therapy compares favorably with other more expensive and time-consuming therapies that have been reported in the literature Cranial asymmetries due to nonsynostotic deformation of the skull have been reported with increasing frequency during the last decade . Conservative approaches using helmets and physiotherapy have been shown to be effective in their treatment . Traditionally , documentation has been carried out using anthropometric caliper measurements . The present study evaluates the use of a new three-dimensional photographic system in the improved validation of changes in head deformities . This prospect i ve analysis introduces a new technique for digital anthropometric measurement . The study series comprised 181 children with nonsynostotic head deformities . Three-dimensional photographs were obtained before and after treatment with an orthotic helmet device . The oblique head diagonals and head width and length were measured from three-dimensional photographs using 3dMD customer software . The cranial vault asymmetry index , cranial vault asymmetry , and cranial index were compared before and after treatment . The measurements obtained on three-dimensional images were able to demonstrate significant improvement in early infant cranial deformity after treatment with an orthotic helmet . The cranial vault asymmetry index in plagiocephaly was reduced by 7.16 % , and cranial vault asymmetry was reduced by 0.86 cm . The cranial index in brachycephaly decreased by 7.32 % . In children with combined plagiocephaly and brachycephaly , the cranial vault asymmetry index improved by 5.77 % , cranial vault asymmetry improved by 0.71 cm , whereas the cranial index changed by 5.48 % . Three-dimensional photogrammetry can support treatment control in patients with deformational plagiocephaly . This new technology offers several advantages such as easy acquisition of images , detection of l and marks without patient movement , repeatable measurements without patient discomfort , and the opportunity for unbiased evaluation . Abbreviations : CVAI , cranial vault asymmetry index ; CVA , cranial vault asymmetry ; CI , cranial Background The child with posterior plagiocephaly may have positional molding or unilateral lambdoid synostosis . Molding responds to conservative treatment , lambdoid synostosis requires surgical reconstruction . CT is diagnostic , but uses ionizing radiation , may need sedation , and the incidence of lambdoid fusion is only 2–3 % . Objective The purpose of this prospect i ve study was to evaluate ultrasound as a screening test of lambdoid sutural patency using CT as the reference st and ard . Material s and methods In total , 41 children having head CT examinations were enrolled over 6 months . Of those , 29 were referred for abnormal head shape and suspected synostosis , of whom two had lambdoid fusion ; 12 were referred for indications not related to head shape and found to have a normal study . Ultrasound scanning and interpretation of the lambdoid sutures was performed blinded to the CT reference st and ard . The lambdoid suture was read as patent or fused if a hypoechoic gap could or could not be seen between the hyperechoic calvarial bones , respectively . Results The mean sensitivity and specificity of ultrasound in distinguishing a patent from fused lambdoid suture by three blinded pediatric radiologists was 100 % and 89 % , respectively . Conclusions Sonography of the lambdoid sutures shows excellent preliminary promise as a screening test of lambdoid sutural patency Objective Unilateral positional plagiocephaly is the most common deformity of the head in infants . As part of a prospect i ve controlled clinical study , the pathomorphology of the positional plagiocephaly in early infancy was examined . The goal was to use noninvasive three-dimensional ( 3D ) imaging to generate , for the first time ever , a st and ard data base of infants without head deformities , to quantify the asymmetry of the positional plagiocephaly , and to evaluate the effectiveness of functional growth control using head orthesis . Patients and methods In the present study , 3D soft-tissue data of the entire head were collected from a total of 40 infants : 20 with positional plagiocephaly ( 6.0 ± 0.97 months ) and 20 infants without a head deformity ( 6.4 ± 0.3 months ) . Functional growth was controlled using a custom-made head orthesis . To evaluate the therapy , pre- and posttherapeutic scans were evaluated in three dimensions . Results Compared with the control group , infants with positional plagiocephaly demonstrated a reduced maximum length of the head , an increased head height , a shift in the ear axis as well as asymmetric anterior and posterior volumes of the neurocranium in lateral comparisons . Therapy using head orthesis led to a significant improvement of the asymmetry , with a reduction of the diagonal difference and an adjustment of the posterior volumes . Conclusion Conservative growth control of extrinsically deformed infant skulls represents an interdisciplinary medical expansion of the orthodontic therapeutic spectrum . To prevent potential effects of positional plagiocephaly on the viscerocranium , head orthesis therapy is advisable in infancy . ZusammenfassungZielDer einseitige lagerungsbedingte Plagiozephalus ist die häufigste Kopfdeformität i m Säuglingsalter . I m Rahmen einer prospektiv kontrollierten klinischen Studie wurde die Pathomorphologie des Lagerungsplagiozephalus i m Säuglingsalter untersucht . Ziel war es , durch Einsatz der nichtinvasiven dreidimensionalen Bildgebung erstmals eine Norm date nbank von Säuglingen ohne Kopfdeformitäten zu generieren , die Asymmetrie des Lagerungsplagiozephalus zu quantifizieren und die Effektivität der funktionellen Wachstumssteuerung mittels Kopforthese zu evaluieren . Patienten und Method ikInsgesamt wurden von 40 Säuglinge ( 20 Säuglinge mit Lagerungsplagiozephalus : 6,0 ± 0,97 Monate , 20 Säuglinge ohne Kopfdeformität : 6,4 ± 0,3 Monate ) die 3D-Weichteil date n des gesamten Kopfes erhoben . Die funktionelle Wachstumssteuerung erfolgte mittels individuell angefertigter Kopforthese . Zur Evaluation der Therapie wurden die prä- und posttherapeutischen Scans dreidimensional ausgewertet . ErgebnisseSäuglinge mit Lagerungsplagiozephalus wiesen gegenüber der Kontrollgruppe eine reduzierte maximale Kopflänge , eine vergrößerte Kopfhöhe und eine Verschiebung der Ohrachse auf sowie i m Seitenvergleich asymmetrische anteriore und posteriore Volumina des Neurokraniums . Die Therapie mittels Kopforthese führte zu einer signifikanten Verbesserung der Asymmetrie mit Reduktion der Diagonalendifferenz und Angleichung der posterioren Volumina . SchlussfolgerungDie konservative Wachstumssteuerung des extrinsisch deformierten Säuglingsschädels stellt eine interdisziplinäre medizinisch-relevante Ausweitung des kieferorthopädischen Spektrums dar . Um potenzielle Folgen des Lagerungsplagiozephalus auf das Viszerokranium zu verhindern ist eine Kopforthesentherapie i m Säuglingsalter angezeigt Appropriate management of posterior plagiocephaly requires differentiation of occipitoparietal flattening caused by lambdoid synostosis from that caused by deformational forces . In a 2 1/2-year prospect i ve study of 115 infants presenting with unilateral posterior cranial flattening , only one child had synostotic posterior plagiocephaly ( lambdoid synostosis ) , whereas 114 infants had deformational posterior plagiocephaly . Deformational occipitoparietal flattening was more common on the right ( 61 percent ) than on the left ( 30 percent ) , and minor contralateral frontal flattening was not unusual ( 52 percent ) . The ipsilateral ear was anteriorly displaced in virtually all infants ( 97 percent ) . Some infants had ipsilateral torticollis ( 19 percent ) ; a few had contralateral torticollis ( 8 percent ) . Gender ratio was 3:1 , male : female . A total of 114 infants with deformational posterior plagiocephaly were treated conservatively either by head positioning in the crib ( n = 63 ) or with a molding helmet ( n = 51 ) . Outcome was assessed by pretreatment and posttreatment anthropometry on 53 of these infants , who were either positioned ( n = 17 ) or helmeted ( n = 36 ) . Improvement occurred in 52 of 53 patients ( mean follow-up 4.6 months ) , i.e. , the difference in length between the long and short transcranial axis diminished in 52 infants ( mean 1.2 to 0.7 cm ) , did not progress in any child , and was unchanged in one infant . At an average age of 10 months , posterior cranial symmetry was better in infants treated with a helmet ( mean difference 0.6 cm ) than in those managed by positioning ( mean difference 1.0 cm ) ( p < 0.001 ) . Age at initiation of helmet therapy ( from 2 to 9 months ) was unrelated to rate of improvement . In a 10-year retrospective study , the authors identified 12 infants who had an operation for posterior plagiocephaly . All but one had confirmed premature lambdoid fusion ; thus , this condition accounted for 3.4 percent of all primary operations performed for craniosynostosis during this decade ( n = 323 ) . In retrospect , the physical findings of synostotic posterior plagiocephaly were not clearly different from those of deformational posterior plagiocephaly . Plain radiography was sometimes used to confirm the clinical diagnosis . Neither sutural narrowing , deep interdigitations , nor perisutural sclerosis indicated lambdoid synostosis . Computed tomography ( CT ) was necessary if the physical findings were suspicious for lambdoid synostosis or if plain films did not give a definitive diagnosis . Axial CT scans ( n = 7 ) showed a symmetric forehead in all but one patient with lambdoid synostosis . CT studies also demonstrated that auricular position was indeterminate in synostotic posterior plagiocephaly , being anterior , posterior , or symmetric , whereas the ipsilateral ear was virtually always anterior in deformational posterior plagiocephaly OBJECTIVE The management of infants with posterior plagiocephaly has been controversial both because of widely differing estimates in the literature of the relative frequencies of true lambdoidal synostosis vs positional molding and because of divergent approaches to treating this problem in different institutions . Based on our experience , we hypothesized that the vast majority of children with posterior plagiocephaly did not have true synostosis and that the cosmetic impairment in such patients could be effectively treated with nonsurgical modalities . METHODS Between 1992 and 1995 , we prospect ively applied in 71 infants a consistent management philosophy for these malformations that has incorporated a detailed evaluation of sutural anatomy as the basis for a physiologic approach to treatment . This approach has been directed at distinguishing true synostosis from deformational plagiocephaly and at avoiding surgery for patients with deformational abnormalities by using a combination of nonsurgical modalities to restore normal cranial growth dynamics . All children first underwent skull radiographs to determine whether the lambdoidal sutures were patent . In equivocal cases , computed tomography was also performed . Patients without true synostosis were enrolled on a course of positional therapy . In patients that did not improve after 2 to 3 months , a custom-fitted orthoplastic molding helmet was applied to facilitate passive skull recontouring . RESULTS Forty children had patent sutures based on skull radiographs , and 29 others , in whom the radiographs were equivocal , had open sutures based on computed tomography , thus establishing the diagnosis of deformational plagiocephaly in 69 . Predisposing factors for this deformity included a strong positioning preference during early infancy ( n = 67 ) , torticollis ( n = 10 ) , prematurity ( n = 6 ) , and developmental delay ( n = 2 ) . Only two patients had true lambdoidal synostosis ; in each case , this was associated with synostosis of the posterior sagittal suture and was managed effectively with cranial reconstructive surgery . Thirty-five patients with deformational plagiocephaly had a dramatic improvement in their cranial contour with positional therapy alone ; 34 patients failed to improve and were treated with molding helmets . All but five children , each of whom was more than 6 months old at initial intervention ( P < .025 ) , developed a normal or nearly normal head shape with these measures . CONCLUSION The vast majority of children with posterior plagiocephaly do not have true synostosis and can be effectively managed by nonsurgical means . The impact of positional preference on the development of this process is discussed BACKGROUND AND PURPOSE : Orthotic helmets and active repositioning are the most common treatments for deformational plagiocephaly ( DP ) . Existing evidence is not sufficient to objective ly inform decisions between these options . A three-dimensional ( 3D ) , whole-head asymmetry analysis was used to rigorously compare outcomes of these 2 treatment methods . PATIENTS AND METHODS : Whole-head 3D surface scans of 70 infants with DP were captured before and after treatment by using stereophotogrammetric imaging technology . Helmeted ( n = 35 ) and nonhelmeted/actively repositioned ( n = 35 ) infants were matched for severity of initial deformity . Surfaces were spatially registered to a symmetric template , which was deformed to achieve detailed right-to-left point correspondence for every point on the head surface . A ratiometric asymmetry value was calculated for each point relative to its contralateral counterpart . Maximum and mean asymmetry values were determined . Change in mean and maximum asymmetry with treatment was the basis for group comparison . RESULTS : The helmeted group had a larger reduction than the repositioned group in both maximum ( 4.0 % vs 2.5 % ; P = .02 ) and mean asymmetry ( 0.9 % vs 0.5 % ; P = .02 ) . The greatest difference was localized to the occipital region . CONCLUSIONS : Whole-head 3D asymmetry analysis is capable of rigorously quantifying the relative efficacy of the 2 common treatments of DP . Orthotic helmets provide statistically superior improvement in head symmetry compared with active repositioning immediately after therapy . Additional studies are needed to ( 1 ) establish the clinical significance of these quantitative differences in outcome , ( 2 ) define what constitutes pathologic head asymmetry , and ( 3 ) determine whether superiority of orthotic treatment lasts as the child matures OBJECTIVE Given the increasing incidence of deformational plagiocephaly due to infants ' supine sleeping position to prevent sudden infant death syndrome , reliable anthropometric diagnostics are needed . Besides the traditional method of measuring l and marks with callipers , three-dimensional ( 3D ) photography has great potential . In this investigation the accuracy of 3D photogrammetry is studied . METHODS The study included 100 r and omly chosen children between the ages of 4 and 20 months with a non-synostotic cranial deformity in a retrospective analysis . Measurements of diagonals A and B on the infant 's head were obtained once using callipers . 3D photographs of these children were measured 5 times by 5 clinicians separately . RESULTS The inter- and intra-rater agreements of the 3D measurements had low variability in the variance component analysis . The st and ard deviations for reproducibility and repeatability were 0.117 - 0.283 cm for diagonals A and B. The intra-class correlation coefficients for the inter-rater reliability result ed in excellent agreement ( 0.97 for plagiocephaly , 0.98 for brachycephaly , 0.96 for combined deformity ) . The comparison of the 3D photographic and callipers measurements showed that 3D photography result ed in a slight over-estimation . CONCLUSION 3D photogrammetry is potentially a reliable tool for treatment planning and follow-up of abnormal head shapes in infancy |
11,161 | 25,896,573 | A key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel .
Although the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £ 20,000 to £ 30,000 per QALY gained , the long-term modelling is vulnerable to major assumptions regarding long-term gains . | BACKGROUND Acute coronary syndromes ( ACSs ) are life-threatening conditions associated with acute myocardial ischaemia .
There are three main types of ACS : ST segment elevation myocardial infa rct ion ( STEMI ) , non-ST segment elevation myocardial infa rct ion ( NSTEMI ) and unstable angina ( UA ) .
One treatment for ACS is percutaneous coronary intervention ( PCI ) plus adjunctive treatment with antiplatelet drugs .
Dual therapy antiplatelet treatment [ aspirin plus either prasugrel ( Efient ( ® ) , Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd ) , clopidogrel or ticagrelor ( Brilique ( ® ) , AstraZeneca ) ] is st and ard in UK clinical practice .
Prasugrel is the focus of this review .
OBJECTIVES The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182 . | OBJECTIVES The objective of this study was to characterize the bleeding , transfusion , and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting ( CABG ) . BACKGROUND There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG . Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved . METHODS A subset of the TRITON-TIMI 38 study ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infa rct ion 38 ) , in which patients with acute coronary syndrome were r and omized to treatment with aspirin and either clopidogrel or prasugrel , underwent isolated CABG ( N = 346 ) . A supplemental case report form was design ed and administered , and the data combined with the existing TRITON-TIMI 38 data base . Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm . RESULTS A significantly higher mean 12-h chest tube blood loss ( 655 ± 580 ml vs. 503 ± 378 ml ; p = 0.050 ) was observed with prasugrel compared with clopidogrel , without significant differences in red blood cell transfusion ( 2.1 U vs. 1.7 U ; p = 0.442 ) or the total donor exposure ( 4.4 U vs. 3.0 U ; p = 0.463 ) . All-cause mortality was significantly reduced with prasugrel ( 2.31 % ) compared with 8.67 % with clopidogrel ( adjusted odds ratio : 0.26 ; p = 0.025 ) . CONCLUSIONS Despite an increase in observed bleeding , platelet transfusion , and surgical re-exploration for bleeding , prasugrel was associated with a lower rate of death after CABG compared with clopidogrel INTRODUCTION The antiplatelet effect of st and ard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infa rct ion ( STEMI ) has never been studied . In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention ( PCI ) . MATERIAL S AND METHODS Fifty-four patients with STEMI undergoing PCI were r and omly allocated to receive either 75 mg/day clopidogrel ( group 1 ) or 150 mg/day ( group 2 ) for 1 month . Platelet function , measured by 5 different assays , was determined at 3 time points : 38+/-8 hours after the procedure , 1 week and 1 month after r and omization . RESULTS In group 1 , mean + /- SD platelet reactivity index ( PRI ) measured with the VASP assay was 57.7+/-15.7 % and 46.9+/-15.7 % at 1 week and 1 month , respectively , compared to 38.8+/-15.7 % and 34.9+/-12.6 % in group 2 ( p=0.0001 ) . Same results were observed for light transmittance aggregometry , whole blood aggregometry and VerifyNow , but not for thromboelastometry . In contrast to what may be expected , the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect . Furthermore , patients in group 2 had a nearly 50 % reduction in C-reactive protein levels both at 1 week and 1 month . CONCLUSION In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation The r and omized TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infa rct ion ( TRITON-TIMI ) 38 trial compared prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention ( PCI ) . Patients treated with prasugrel had fewer ischemic events but more procedure-related bleeding . In the present study , we aim ed to determine the effect of bivalirudin on bleeding in patients treated with prasugrel . A total of 692 patients with consecutive acute coronary syndrome underwent PCI with stent implantation and were anticoagulated with bivalirudin . The patients were divided into 2 groups according to the antiplatelet regimen ( clopidogrel or prasugrel ) chosen during or just after PCI . The bleeding complications during hospitalization were tabulated . Ischemic events were analyzed during hospitalization and at 30 days . Prasugrel was used in 96 patients ( 13.9 % ) and clopidogrel in 596 ( 86.1 % ) . The clinical and procedural characteristics were similar , although the clopidogrel patients more often reported systemic hypertension ( p = 0.01 ) , previous PCI ( p < 0.001 ) , and chronic renal insufficiency ( p = 0.05 ) . During hospitalization , the bleeding and ischemic complication rates were similar and low in both groups ( major in-hospital complications 4.2 % for clopidogrel vs 2.1 % for prasugrel , p = 0.6 ; Thrombolysis In Myocardial Infa rct ion major bleeding 2.5 % vs 2.1 % , p = 1.00 ; Thrombolysis In Myocardial Infa rct ion minor bleeding 4.2 % vs 5.2 % , p = 0.6 ) . At 30 days , no differences were found in ischemic events between both groups ( target vessel revascularization/major adverse cardiac events 5.4 % vs 2.1 % , p = 0.2 ) . In conclusion , prasugrel , when given after bivalirudin as the intraprocedural antithrombin agent for patients with acute coronary syndrome undergoing PCI , is as safe and effective as clopidogrel Background Although unstable coronary artery disease is the most common reason for admission to a coronary care unit , the long-term prognosis of patients with this diagnosis is unknown . This is particularly true for patients with diabetes mellitus , who are known to have a high morbidity and mortality after an acute myocardial infa rct ion . Methods and Results Prospect ively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes ( OASIS ) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non – Q-wave myocardial infa rct ion . Overall , 1718 of 8013 registry patients ( 21 % ) had diabetes . Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients ( 23 % versus 20 % , P < 0.001 ) but had similar rates of catheterization and angioplasty . Diabetes independently predicted mortality ( relative risk [ RR ] , 1.57 ; 95 % CI , 1.38 to 1.81;P < 0.001 ) , as well as cardiovascular death , new myocardial infa rct ion , stroke , and new congestive heart failure . Moreover , compared with their nondiabetic counterparts , women had a significantly higher risk than men ( RR , 1.98 ; 95 % CI , 1.60 to 2.44 ; and RR , 1.28 ; 95 % CI , 1.06 to 1.56 , respectively ) . Interestingly , diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease . Conclusions Hospitalization for unstable angina or non – Q-wave myocardial infa rct ion predicts a high 2-year morbidity and mortality ; this is especially evident for patients with diabetes . Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background —Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel . Direct pharmacodynamic comparison between them has not yet been reported in ST-segment – elevation myocardial infa rct ion patients . Methods and Results —In a prospect i ve , single-center , single-blind study , 55 out of 117 ( 47 % ) screened consecutive ST-segment – elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention were r and omized to either ticagrelor 180 mg loading followed by 90 mg bid , or prasugrel 60 mg loading followed by 10 mg od for 5 days . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0 , 1 , 2 , 6 , 24 hours , and 5 days postr and omization . The primary end point , PR with VerifyNow at hour 1 , did not differ significantly between patients r and omized to ticagrelor versus prasugrel ( 257.3 P2Y12 reaction unit [ PRU ] , 95 % CI 230.8–283.8 versus 231.3 PRU , 95 % CI 205.3–257.4 ; P=0.2 ) . PR did not differ at 2 , 6 , and 24 hours , although at day 5 it was lower with ticagrelor than prasugrel ( 25.6 PRU , 95 % CI 12.3–38.9 versus 50.3 PRU , 95 % CI 36.4–64.1 ; P=0.01 ) . At hour 2 , high on-treatment PR rates ( cutoff 208 PRU ) were 46.2 % and 34.6 % for ticagrelor and prasugrel , respectively , decreased significantly thereafter , whereas did not differ significantly between the 2 agents at all the time points of the study . Conclusions —In patients with ST-segment – elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention , both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action . Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01463163 BACKGROUND Recurrent ischemic events occurred even during routine use of 75 mg clopidogrel in addition to aspirin , that indicated a potentially insufficient maintenance dosage of clopidogrel . The aim of the present study was to evaluate the short-term efficacy and safety of a 150 mg maintenance dose of clopidogrel following a 600 mg loading dose in patients with an acute coronary syndrome ( ACS ) undergoing drug eluting stent ( DES ) implantation . METHODS Between November 2005 and November 2006 , a total of 813 consecutive ACS patients undergoing DES implantation were enrolled . A 600 mg loading dose was administered before percutaneous coronary intervention ( PCI ) and patients were r and omized to receive clopidogrel 75 mg or 150 mg for 30 days in addition to 300 mg aspirin daily . Primary end points were the composite of cardiac death , non-fatal myocardial infa rct ion ( MI ) and urgent target vessel revascularization ( UTVR ) . Secondary end points included stent thrombosis ( ST ) , major and minor bleeding events at 30 days . RESULTS At a follow-up period of 30 days , 4 ( 1.0 % ) patients in the 150 mg group and 9 ( 2.2 % ) patients in the 75 mg group ( P > 0.05 ) reached the primary end points . There was no significant difference in the incidences of MI ( 0.5 % vs 1.2 % , P > 0.05 ) , UTVR ( 0.7 % vs 2.0 % , P > 0.05 ) , and cardiac death ( 0.2 % vs 0.2 % , P > 0.05 ) between the two groups . The incidence of ST ( 0 vs 1.5 % , P < 0.05 ) was significantly lower in the 150 mg group than that in the 75 mg group . There were no significant differences between both groups regarding the risk of major ( 0.2 % vs 0 , P > 0.05 ) or minor ( 0.5 % vs 0.2 % , P > 0.05 ) bleedings . CONCLUSION A high clopidogrel maintenance dose of 150 mg daily following a 600 mg loading dose for the first month after PCI procedure reduces the risk of ST and appears to be safe in patients with ACS undergoing DES implantation OBJECTIVES Our goal was to compare the safety and initial efficacy of AZD6140 , the first reversible oral adenosine diphosphate receptor antagonist , with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . BACKGROUND AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease . METHODS A total of 990 patients with NSTE-ACS , treated with aspirin and st and ard therapy for ACS , were r and omized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg , AZD6140 180 mg , or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks . RESULTS The primary end point , the Kaplan-Meier rate of major or minor bleeding through 4 weeks , was 8.1 % in the clopidogrel group , 9.8 % in the AZD6140 90-mg group , and 8.0 % in the AZD6140 180-mg group ( p = 0.43 and p = 0.96 , respectively , vs. clopidogrel ) ; the major bleeding rates were 6.9 % , 7.1 % , and 5.1 % , respectively ( p = 0.91 and p = 0.35 , respectively , vs. clopidogrel ) . Although not statistically significant , favorable trends were seen in the Kaplan-Meier rates of myocardial infa rct ion ( MI ) over the entire study period ( MI : 5.6 % , 3.8 % , and 2.5 % , respectively ; p = 0.41 and p = 0.06 , respectively , vs. clopidogrel ) . In a post-hoc analysis of continuous electrocardiograms , mostly asymptomatic ventricular pauses > 2.5 s were more common , especially in the AZD6140 180-mg group ( 4.3 % , 5.5 % , and 9.9 % , respectively ; p = 0.58 and p = 0.01 , respectively , vs. clopidogrel ) . CONCLUSIONS This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI . This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS AIMS To examine the extent of platelet inhibition by prasugrel vs. clopidogrel in a TRITON-TIMI 38 sub study . METHODS AND RESULTS TRITON-TIMI 38 r and omized acute coronary syndrome ( ACS ) patients undergoing percutaneous coronary intervention ( PCI ) to prasugrel or st and ard dose clopidogrel . Selected sites prospect ively enrolled TRITON-TIMI 38 patients to evaluate adenosine diphosphate (ADP)-attenuated phosphorylation of platelet vasodilator-stimulated phosphoprotein ( VASP ) ( n = 125 patients ) and , in a subset ( n = 31 patients ) , ADP-stimulated platelet aggregation . VASP platelet reactivity index ( PRI ) was lower in prasugrel-treated patients than in clopidogrel-treated patients at 1 - 2 h post-PCI ( > or=1 h after loading dose ) ( P < 0.001 ) and at 30 days ( P < 0.001 ) . Maximal platelet aggregation to 20 microM ADP was lower in prasugrel-treated patients than in clopidogrel-treated patients at 1 - 2 h ( P = 0.004 ) and 30 days ( P = 0.03 ) . Results were similar with 5 microM ADP . Thienopyridine hyporesponsiveness , prespecified as VASP PRI > 50 % , was more frequent in clopidogrel-treated patients than in prasugrel-treated patients at 1 - 2 h ( P < 0.001 ) and 30 days ( P = 0.03 ) . CONCLUSIONS The TRITON-TIMI 38 platelet sub study shows that prasugrel results in greater inhibition of ADP-mediated platelet function in ACS patients than clopidogrel , supporting the hypothesis that greater platelet inhibition leads to a lower incidence of ischaemic events and more bleeding both early and late following PCI BACKGROUND Despite current treatments , patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events . We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients . METHODS We r and omly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel ( 300 mg immediately , followed by 75 mg once daily ) ( 6259 patients ) or placebo ( 6303 patients ) in addition to aspirin for 3 to 12 months . RESULTS The first primary outcome --a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group ( relative risk with clopidogrel as compared with placebo , 0.80 ; 95 percent confidence interval , 0.72 to 0.90 ; P<0.001 ) . The second primary outcome --the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group ( relative risk , 0.86 ; 95 percent confidence interval , 0.79 to 0.94 ; P<0.001 ) . The percentages of patients with in-hospital refractory or severe ischemia , heart failure , and revascularization procedures were also significantly lower with clopidogrel . There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group ( 3.7 percent vs. 2.7 percent ; relative risk , 1.38 ; P=0.001 ) , but there were not significantly more patients with episodes of life-threatening bleeding ( 2.2 percent [ corrected ] vs. 1.8 percent ; P=0.13 ) or hemorrhagic strokes ( 0.1 percent vs. 0.1 percent ) . CONCLUSIONS The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation . However , the risk of major bleeding is increased among patients treated with clopidogrel BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . OBJECTIVES We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the st and ard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day . BACKGROUND Patients show interindividual variability in their platelet response to clopidogrel . Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel . METHODS One hundred fifty-three elective percutaneous coronary intervention patients were r and omized to clopidogrel 150 mg/day ( n = 58 ) or 75 mg/day ( n = 95 ) for 4 weeks , with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders ( platelet reactivity index > or=69 % ) . All patients received aspirin 75 mg/day . RESULTS After 2 weeks , clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day ( 43.9 + /- 17.3 % vs. 58.6 + /- 17.7 % ; p < 0.0001 ) . The proportion of low responders was significantly lower in patients r and omized to clopidogrel 150 mg/day than in those r and omized to clopidogrel 75 mg/day ( 8.6 % vs. 33.7 % ; p = 0.0004 ) . In the clopidogrel 75 mg/day group , 64.5 % ( 20 of 31 ) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks . No major bleeds occurred during the study ; the incidence of minor bleeds was similar in each treatment group . CONCLUSIONS In elective percutaneous coronary intervention patients , a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day . In low responders to clopidogrel 75 mg/day , switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients . These findings warrant further clinical evaluation . ( VASP-02 ; EudraCT number : 2004 - 005230 - 40 ) BACKGROUND Among patients with acute coronary syndrome ( ACS ) , demographics , procedural characteristics and adjunctive medications differ globally . We examined whether there were differential effects of prasugrel compared with clopidogrel in the multinational TRITON-TIMI 38 study . METHODS We divided the enrollment into 5 pre-specified geographic regions . Patients were r and omized to prasugrel or clopidogrel without regard to country of enrollment . End points are expressed as Kaplan-Meier failure estimates through 15 months . Heterogeneity was evaluated using Cox proportional hazards model . Additional sensitivity analyses were performed by dividing countries into categories based on the Human Development Index ( HDI ) , which is a composite measure of social and economic development . RESULTS 13,608 patients were enrolled . Clinical characteristics including age , comorbidities , ACS presentation , stent types , and adjunctive medications differed broadly among regions . Despite these differences , no regional heterogeneity was observed with prasugrel compared to clopidogrel in the reduction of ischemic events ( HR range : 0.76 - 0.87 , p(interaction)>0.10 for each ) and stent thrombosis ( HR range : 0.34 - 0.72 , p(interaction)>0.10 for each ) or in the increased rate of non-CABG TIMI major bleeding ( HR range : 1.16 - 1.76 , p(interaction)>0.10 for each ) . There was a consistent trend in net clinical benefit ( all cause death/MI/stroke/non-CABG TIMI major bleeding ) favoring prasugrel ( HR range : 0.81 - 0.97 , p(interaction)>0.10 for each ) . Consistent results were also observed regarding the safety and efficacy of prasugrel compared with clopidogrel in both developed and developing countries . CONCLUSIONS Despite differences in patient demographics , procedural techniques and adjunctive medications , consistent reduction in ischemic events and increased bleeding were seen with prasugrel compared with clopidogrel throughout the world BACKGROUND Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes . We compared ticagrelor , a more potent reversible P2Y12 inhibitor with clopidogrel in such patients . METHODS At r and omisation , an invasive strategy was planned for 13 408 ( 72.0 % ) of 18 624 patients hospitalised for acute coronary syndromes ( with or without ST elevation ) . In a double-blind , double-dummy study , patients were r and omly assigned in a one-to-one ratio to ticagrelor and placebo ( 180 mg loading dose followed by 90 mg twice a day ) , or to clopidogrel and placebo ( 300 - 600 mg loading dose or continuation with maintenance dose followed by 75 mg per day ) for 6 - 12 months . All patients were given aspirin . The primary composite endpoint was cardiovascular death , myocardial infa rct ion , or stroke . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00391872 . FINDINGS 6732 patients were assigned to ticagrelor and 6676 to clopidogrel . The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group ( 569 [ event rate at 360 days 9.0 % ] vs 668 [ 10.7 % ] , hazard ratio 0.84 , 95 % CI 0.75 - 0.94 ; p=0.0025 ) . There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding ( 691 [ 11.6 % ] vs 689 [ 11.5 % ] , 0.99 [ 0.89 - 1.10 ] ; p=0.8803 ) or severe bleeding , as defined according to the Global Use of Strategies To Open occluded coronary arteries , ( 198 [ 3.2 % ] vs 185 [ 2.9 % ] , 0.91 [ 0.74 - 1.12 ] ; p=0.3785 ) . INTERPRETATION Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned BACKGROUND Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention ( PCI ) . We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI . METHODS The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries . 25,086 individuals with acute coronary syndromes and intended early PCI were r and omly assigned to double-dose ( 600 mg on day 1 , 150 mg on days 2 - 7 , then 75 mg daily ) versus st and ard-dose ( 300 mg on day 1 then 75 mg daily ) clopidogrel , and high-dose ( 300 - 325 mg daily ) versus low-dose ( 75 - 100 mg daily ) aspirin . R and omisation was done with a 24 h computerised central automated voice response system . The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes . This prespecified analysis is of the 17,263 individuals who underwent PCI . The primary outcome was cardiovascular death , myocardial infa rct ion , or stroke at 30 days . Analyses were by intention to treat , adjusted for propensity to undergo PCI . This trial is registered with Clinical Trials.gov , number NCT00335452 . FINDINGS 8560 patients were assigned to double-dose and 8703 to st and ard-dose clopidogrel ( 8558 and 8702 completed 30-day follow-up , respectively ) , and 8624 to high-dose and 8639 to low-dose aspirin ( 8622 and 8638 completed 30-day follow-up , respectively ) . Compared with the st and ard dose , double-dose clopidogrel reduced the rate of the primary outcome ( 330 events [ 3·9 % ] vs 392 events [ 4·5 % ] ; adjusted hazard ratio 0·86 , 95 % CI 0·74 - 0·99 , p=0·039 ) and definite stent thrombosis ( 58 [ 0·7 % ] vs 111 [ 1·3 % ] ; 0·54 [ 0·39 - 0·74 ] , p=0·0001 ) . High-dose and low-dose aspirin did not differ for the primary outcome ( 356 [ 4·1 % ] vs 366 [ 4·2 % ] ; 0·98 , 0·84 - 1·13 , p=0·76 ) . Major bleeding was more common with double-dose than with st and ard-dose clopidogrel ( 139 [ 1·6 % ] vs 99 [ 1·1 % ] ; 1·41 , 1·09 - 1·83 , p=0·009 ) and did not differ between high-dose and low-dose aspirin ( 128 [ 1·5 % ] vs 110 [ 1·3 % ] ; 1·18 , 0·92 - 1·53 , p=0·20 ) . INTERPRETATION In patients undergoing PCI for acute coronary syndromes , a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the st and ard dose . Efficacy and safety did not differ between high-dose and low-dose aspirin . A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI . FUNDING Sanofi-Aventis and Bristol-Myers Squibb BACKGROUND The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful , and whether these compounds can be used to reduce disability after recurrent stroke is unknown . The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes ( PRoFESS ) trial . METHODS Patients who had had an ischaemic stroke were r and omly assigned in a two by two factorial design to receive either 25 mg aspirin ( ASA ) and 200 mg extended-release dipyridamole ( ER-DP ) twice a day or 75 mg clopidogrel once a day , and either 80 mg telmisartan or placebo once per day . The predefined endpoints for this sub study were disability after a recurrent stroke , assessed with the modified Rankin scale ( mRS ) and Barthel index at 3 months , and cognitive function , assessed with the mini-mental state examination ( MMSE ) score at 4 weeks after r and omisation and at the penultimate visit . Analysis was by intention to treat . The study was registered with Clinical Trials.gov , number NCT00153062 . FINDINGS 20,332 patients ( mean age 66 years ) were r and omised and followed-up for a median of 2.4 years . Recurrent strokes occurred in 916 ( 9 % ) patients r and omly assigned to ASA with ER-DP and 898 ( 9 % ) patients r and omly assigned to clopidogrel ; 880 ( 9 % ) patients r and omly assigned to telmisartan and 934 ( 9 % ) patients given placebo had recurrent strokes . mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel ( p=0.38 ) , or with telmisartan versus placebo ( p=0.61 ) . There was no significant difference in the proportion of patients with recurrent stroke with a good outcome , as measured with the Barthel index , across all treatment groups . Additionally , there was no significant difference in the median MMSE scores , the percentage of patients with an MMSE score of 24 points or less , the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit , and the number of patients with dementia among the treatment groups . There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups . INTERPRETATION Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan OBJECTIVES This study sought to assess the independent contribution of nonfatal reinfa rct ion to the risk of subsequent death in patients with acute myocardial infa rct ion undergoing thrombolytic therapy . BACKGROUND A composite of " unsatisfactory outcomes " as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infa rct ion . The significance of nonfatal reinfa rct ion as a component of a composite end point has not been evaluated in the thrombolytic era . METHODS Event rate of nonfatal reinfa rct ion over 3-year follow-up was evaluated in patients with acute myocardial infa rct ion entered into the Thrombolysis in Myocardial Infa rct ion Phase II trial . The independent risk of nonfatal reinfa rct ion for subsequent death within various time intervals of follow-up was determined . The mortality rate after nonfatal reinfa rct ion was compared with that of a matched control group . RESULTS During 3-year follow-up , 349 of 3,339 patients had a nonfatal reinfa rct ion . Univariate predictors were history ( antedating the index event ) of angina ( p = 0.01 ) , hypertension ( p = 0.01 ) , multivessel disease ( p = 0.007 ) and not a current smoker ( p = 0.003 ) ; the latter was an independent predictor ( relative risk [ RR ] 1.3 , 99 % confidence interval [ CI ] 1.0 to 1.8 ) . Forty-three of the 349 patients with a nonfatal reinfa rct ion died : RR for death ( vs. patients without a nonfatal reinfa rct ion ) was 1.9 ( 99 % CI 1.1 to 3.2 ) if reinfa rct ion occurred within 42 days of study entry , 6.2 ( 99 % CI 3.0 to 12.9 ) if reinfa rct ion occurred between 43 and 365 days and 2.9 ( 99 % CI 0.6 to 13.4 ) if reinfa rct ion occurred between 366 days and 3 years . The cumulative 3-year death rate was 14.1 % in patients with a nonfatal reinfa rct ion compared with 7.9 % ( p < 0.01 ) in a matched control group . Univariate predictors of death after nonfatal reinfa rct ion were age > or = 65 years ( p < 0.001 ) , not low risk category ( p = 0.015 ) and history of heart failure before the index event ( p < 0.001 ) . Age > or = 65 years was the only independent predictor ( RR 5.4 , 99 % CI 2.3 to 12.4 ) . CONCLUSIONS Nonfatal reinfa rct ion is a strong and independent predictor for subsequent death . It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infa rct ion Background . Mapping disease-specific instruments into generic health outcomes or utility values is an exp and ing field of interest in health economics . This article constructs an algorithm to translate the modified Rankin scale ( mRS ) into EQ-5D utility values . Methods . mRS and EQ-5D information was derived from stroke or transient ischemic attack ( TIA ) patients identified as part of the Oxford Vascular study ( OXVASC ) . Ordinary least squares ( OLS ) regression was used to predict UK EQ-5D tariffs from mRS scores . An alternative method , using multinomial logistic regression with a Monte Carlo simulation approach ( MLogit ) to predict responses to each EQ-5D question , was also explored . The performance of the models was compared according to the magnitude of their predicted-to-actual mean EQ-5D tariff difference , their mean absolute and mean squared errors ( MAE and MSE ) , and associated 95 % confidence intervals ( CIs ) . Out-of- sample validation was carried out in a subset of coronary disease and peripheral vascular disease ( PVD ) patients also identified as part of OXVASC but not used in the original estimation . Results . The OLS and MLogit yielded similar MAE and MSE in the internal and external validation data sets . Both approaches also underestimated the uncertainty around the actual mean EQ-5D tariff producing tighter 95 % CIs in both data sets . Conclusions . The choice of algorithm will be dependent on the study aim . Individuals outside the United Kingdom may find it more useful to use the multinomial results , which can be used with different country-specific tariff valuations . However , these algorithms should not replace prospect i ve collection of utility data BACKGROUND Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes , but can also increase the rate of thrombotic complications including stent thrombosis . The TRITON-TIMI 38 trial has shown that prasugrel-a novel , potent thienopyridine-can reduce ischaemic events compared with st and ard clopidogrel therapy . We assessed the rate , outcomes , and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON-TIMI 38 study . METHODS Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following r and omisation in TRITON-TIMI 38 , and were further subdivided by type of stent received . Patients were r and omly assigned in a 1 to 1 fashion to receive a loading dose of study drug ( prasugrel 60 mg or clopidogrel 300 mg ) as soon as possible after r and omisation , followed by daily maintenance therapy ( prasugrel 10 mg or clopidogrel 75 mg ) . All patients were to receive aspirin therapy . Treatment was to be continued for a minimum of 6 months and a maximum of 15 months . R and omisation was not stratified by stents used or stent type . The primary endpoint was the composite of cardiovascular death , non-fatal myocardial infa rct ion , or non-fatal stroke . Stent thrombosis was assessed using Academic Research Consortium definitions , and analysis was by intention to treat . TRITON-TIMI 38 is registered with Clinical Trials.gov , number NCT00097591 . FINDINGS 12,844 patients received at least one coronary stent ; 5743 received only drug-eluting stents , and 6461 received only bare-metal stents . Prasugrel compared with clopidogrel reduced the primary endpoint ( 9.7 vs 11.9 % , HR 0.81 , p=0.0001 ) in the stented cohort , in patients with only drug-eluting stents ( 9.0 vs 11.1 % , HR 0.82 , p=0.019 ) , and in patients with only bare-metal stents ( 10.0 vs 12.2 % , HR 0.80 , p=0.003 ) . Stent thrombosis was associated with death or myocardial infa rct ion in 89 % ( 186/210 ) of patients . Stent thrombosis was reduced with prasugrel overall ( 1.13 vs 2.35 % , HR 0.48 , p<0.0001 ) , in patients with drug-eluting stents only ( 0.84 vs 2.31 % , HR 0.36 , p<0.0001 ) , and in those with bare-metal stents only ( 1.27 vs 2.41 % , HR 0.52 , p=0.0009 ) . INTERPRETATION Intensive antiplatelet therapy with prasugrel result ed in fewer ischaemic outcomes including stent thrombosis than with st and ard clopidogrel . These findings were statistically robust irrespective of stent type , and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents Adequate antiplatelet therapy is paramount for good clinical outcomes in patients undergoing percutaneous coronary intervention ( PCI ) . The purpose of this study was to determine whether a high-dose regimen of clopidogrel in patients undergoing PCI is superior to st and ard dosing . A total of 119 patients undergoing PCI were blindly r and omized in 2:1 fashion to receive clopidogrel loading 600 mg on the table immediately before PCI and 75 mg 2 times/day for 1 month ( high-dose group ) versus st and ard dosing ( 300 mg loading and 75 mg/day ; low-dose group ) . Platelet aggregation was measured using light transmission aggregometry at baseline , 4 hours , and 30 days . The composite of cardiovascular death , myocardial infa rct ion , and target vessel revascularization was studied at 30 days in addition to major and minor bleeding . Baseline characteristics and baseline platelet aggregation were similar in the 2 groups . Percent inhibitions of platelet activity were 41 % and 27 % in the high-dose group versus 19 % and 10 % in the low-dose group at 4 hours and 30 days ( p = 0.046 and 0.047 , respectively ) . Composite clinical end points were 10.3 % in the high-dose group and 23.8 % in the low-dose group ( p = 0.04 ) . No difference was noted in major or minor bleeding . In conclusion , a higher loading and maintenance dose of clopidogrel in patients undergoing PCI results in superior platelet inhibition and decreased cardiovascular events without increasing bleeding complications BACKGROUND High on-treatment platelet reactivity ( HTPR ) is present in a substantial percentage of patients on chronic clopidogrel treatment and may have prognostic implication s. Strategies to optimize platelet inhibition in such patients are not clear . METHODS We performed a prospect i ve , single-center , single-blinded , investigator-initiated r and omized , crossover study of platelet inhibition by prasugrel 10 mg/day versus high-dose 150 mg/day clopidogrel , with a 14 day treatment period , in 31 patients with HTPR ( out of 99 screened , 31.3 % ) while on chronic ( ≥ 12 months ) treatment with clopidogrel . All patients had stable coronary artery disease and 87.1 % of them had a prior percutaneous coronary intervention . Platelet reactivity ( PR ) was assessed by the VerifyNow assay measured in platelet reactivity units ( PRU ) . RESULTS The primary end point of PR at the end of the two treatment periods was lower in patients receiving prasugrel compared with high dose clopidogrel ( least squares estimate 148.1 , 95 % CI 127.1 - 169.2 and 219.8 , 95 % CI 198.6 - 240.9 respectively , P < .001 ) . The secondary end point of HTPR rate was lower for prasugrel compared with clopidogrel , 11.5 % vs 46.3 % , P = .003 . CONCLUSIONS Prasugrel appears more effective than double clopidogrel in inhibiting PR in patients with HTPR following chronic clopidogrel treatment BACKGROUND Mechanical reperfusion with stenting for ST-elevation myocardial infa rct ion ( STEMI ) is supported by dual antiplatelet treatment with aspirin and clopidogrel . Prasugrel , a potent and rapid-acting thienopyridine , is a potential alternative to clopidogrel . We aim ed to assess prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention ( PCI ) for STEMI . METHODS We undertook a double-blind , r and omised controlled trial in 707 sites in 30 countries . 3534 participants presenting with STEMI were r and omly assigned by interactive voice response system either prasugrel ( 60 mg loading , 10 mg maintenance [ n=1769 ] ) or clopidogrel ( 300 mg loading , 75 mg maintenance [ n=1765 ] ) and were unaware of the allocation . The primary endpoint was cardiovascular death , non-fatal myocardial infa rct ion , or non-fatal stroke . Efficacy analyses were by intention to treat . Follow-up was to 15 months , with secondary analyses at 30 days . This trial is registered with Clinical Trials.gov , number NCT00097591 . FINDINGS At 30 days , 115 ( 6.5 % ) individuals assigned prasugrel had met the primary endpoint compared with 166 ( 9.5 % ) allocated clopidogrel ( hazard ratio 0.68 [ 95 % CI 0.54 - 0.87 ] ; p=0.0017 ) . This effect continued to 15 months ( 174 [ 10.0 % ] vs 216 [ 12.4 % ] ; 0.79 [ 0.65 - 0.97 ] ; p=0.0221 ) . The key secondary endpoint of cardiovascular death , myocardial infa rct ion , or urgent target vessel revascularisation was also significantly reduced with prasugrel at 30 days ( 0.75 [ 0.59 - 0.96 ] ; p=0.0205 ) and 15 months ( 0.79 [ 0.65 - 0.97 ] ; p=0.0250 ) , as was stent thrombosis . Treatments did not differ with respect to thrombolysis in myocardial infa rct ion ( TIMI ) major bleeding unrelated to coronary-artery bypass graft ( CABG ) surgery at 30 days ( p=0.3359 ) and 15 months ( p=0.6451 ) . TIMI life-threatening bleeding and TIMI major or minor bleeding were also similar with the two treatments , and only TIMI major bleeding after CABG surgery was significantly increased with prasugrel ( p=0.0033 ) . INTERPRETATION In patients with STEMI undergoing PCI , prasugrel is more effective than clopidogrel for prevention of ischaemic events , without an apparent excess in bleeding Background —Despite the current st and ard antiplatelet regimen of aspirin and clopidogrel ( with or without glycoprotein IIb/IIIa inhibitors ) in percutaneous coronary intervention patients , periprocedural and postprocedural ischemic events continue to occur . Prasugrel ( CS-747 , LY640315 ) , a novel potent thienopyridine P2Y12 receptor antagonist , has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel . Methods and Results —Joint Utilization of Medications to Block Platelets Optimally – Thrombolysis In Myocardial Infa rct ion 26 ( JUMBO-TIMI 26 ) was a phase 2 , r and omized , dose-ranging , double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention . Patients were r and omized to either st and ard dosing with clopidogrel or 1 of 3 prasugrel regimens . Subjects were monitored for 30 days for bleeding and clinical events . The primary end point of the trial was clinical ly significant ( TIMI major plus minor ) non – CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients . Hemorrhagic complications were infrequent , with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding ( 1.7 % versus 1.2 % ; hazard ratio , 1.42 ; 95 % CI , 0.40 , 5.08 ) . In prasugrel-treated patients , there were numerically lower incidences of the primary efficacy composite end point ( 30-day major adverse cardiac events ) and of the secondary end points myocardial infa rct ion , recurrent ischemia , and clinical target vessel thrombosis . Conclusions —In this phase 2 study , which was design ed to assess safety when administered at the time of percutaneous coronary intervention , prasugrel and clopidogrel both result ed in low rates of bleeding . The results of this trial serve as a foundation for the large phase 3 clinical trial design ed to assess both efficacy and safety Abstract Background : Prasugrel is a third generation thienopyridine that is more potent , rapid in onset , and consistent in inhibition of platelets than clopidogrel . However , early prasugrel dose-ranging studies and the subsequent phase 3 TRITON-TIMI 38 trial were conducted primarily in Caucasian population s. Objectives : The current clinical study is design ed to confirm superior inhibition of platelet aggregation with prasugrel versus clopidogrel in the treatment of Asian subjects with acute coronary syndrome ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . Research design and methods : This is a phase 3 , r and omized , double-blind , multi-dose , four-arm parallel , multinational clinical trial . East and Southeast Asian patients ( N = 715 ) with moderate- to high-risk ACS undergoing PCI will be r and omized to one of three prasugrel dosing regimens ( 60 mg LD/10 mg MD ; 30 mg LD/7.5 mg MD ; 30 mg LD/5 mg MD ) or clopidogrel ( 300 mg LD/75 mg MD ) for 90 days . Main outcome measures : The primary endpoint is inhibition of platelet aggregation measured by the point-of-care Accumetrics VerifyNow P2Y12 device , and the primary analysis will be performed in a hierarchical manner for descending doses of prasugrel . Additional key endpoints include major adverse cardiovascular events , non-coronary artery bypass-graft ( CABG ) surgery-related TIMI bleeding , and genetic analyses of cytochrome P450 polymorphisms . Conclusions : This study is a phase 3 , multi-dose , pharmacodynamic comparison of prasugrel versus clopidogrel in Asian patients with ACS undergoing PCI . It is the first study design ed to investigate prasugrel therapy specifically in Asian ACS subjects , and will inform which doses of prasugrel are effective and safe for patients of Asian ethnicity . Trial registration : Clinical Trials.gov identifier : NCT00830960 BACKGROUND Prasugrel led to a significant reduction in ischemic cardiovascular events among patients with acute coronary syndrome ( ACS ) undergoing percutaneous coronary intervention ( PCI ) with stent implantation compared to clopidogrel . Whether this benefit extends to patients undergoing PCI without stent implantation is unknown . METHODS In TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel (TRITON)-Thrombolysis in Myocardial Infa rct ion ( TIMI ) 38 , patients ( n = 13 608 ) undergoing PCI for ACS were r and omized to aspirin plus clopidogrel or prasugrel . This postr and omization analysis of a prespecified subgroup was restricted to patients who underwent PCI without stent implantation ( n = 569 ) . RESULTS Patients who underwent PCI without stent implantation were older and had a higher incidence of hypertension , diabetes , prior myocardial infa rct ion ( MI ) , prior coronary artery bypass ( CABG ) surgery , and renal dysfunction than patients who underwent stent implantation . In the group that did not undergo stent implantation , baseline characteristics were similar between patients receiving clopidogrel and prasugrel . The composite of cardiovascular death , nonfatal MI , and nonfatal stroke occurred in 14.2 % of patients receiving prasugrel and 17.1 % of patients receiving clopidogrel ( HR 0.82 , P = .27 ) . There were significant reductions favoring prasugrel in the rates of urgent target vessel revascularization ( TVR ; HR 0.46 , P = .040 ) and any TVR ( HR 0.40 , P = .009 ) and a trend toward a reduction in the incidence of nonfatal MI ( HR 0.65 , P = .11 ) . CABG-related TIMI major bleeding was more frequent among patients receiving prasugrel . There were no significant interactions between treatment and PCI type . CONCLUSION Among ACS patients who underwent PCI without stent implantation , prasugrel therapy tended to reduce clinical ischemic events and to increase bleeding events to a similar magnitude as among patients who received stents BACKGROUND Dual antiplatelet therapy with aspirin and clopidogrel is st and ard for prevention of thrombotic complications of percutaneous coronary intervention ( PCI ) . Prasugrel is a thienopyridine that is more potent , more rapid in onset , and more consistent in inhibition of platelets than clopidogrel . TRITON-TIMI 38 is design ed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome ( ACS ) . STUDY DESIGN TRITON-TIMI 38 is a phase 3 , r and omized , double-blind , parallel-group , multinational , clinical trial . Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI ( 9500 unstable angina/non-ST-segment elevation myocardial infa rct ion [ MI ] , 3500 ST-segment elevation MI ) will be r and omized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months . The primary end point is the time of the first event of cardiovascular death , MI , or stroke . Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and , conditionally , on the whole ACS population . Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery . CONCLUSIONS TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI . In addition , it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the st and ard therapy results in an improvement in clinical outcomes The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition , suggesting the need for a higher dose . The aim of this pilot study was to assess the functional impact of a high ( 150 mg/day ) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention ( PCI ) . This is a prospect i ve , r and omized , platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg ( n = 20 ) or 150 mg ( n = 20 ) daily maintenance dose of clopidogrel for 30 days ; afterwards , all patients resumed st and ard dosing . Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate ( ADP ) stimuli 30 days after r and omization and 30 days after resuming st and ard dosing . Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day ( 52.1 + /- 9 % vs. 64.0 + /- 8 % ; p < 0.001 ; primary endpoint ) . The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming st and ard dosing ( p < 0.001 ) . No changes were observed in patients r and omized to st and ard dosing . Parallel findings were observed following 5 microM ADP stimuli for all assessment s. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing . In conclusion , a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI Purpose . The aim of this study was to analyze quality -of-life data from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) to estimate the impact of diabetes-related complications on utility-based measures of quality of life . Methods . The EuroQol EQ-5D instrument was administered in 1996 to 3667 UKPDS patients with type 2 diabetes . Tobit and censored least absolute deviations ( CLAD ) regression analysis based on data from the 3192 respondents was used to estimate the impact of major complications on ( 1 ) the visual analog scale ( VAS ) and ( 2 ) the EQ-5D utilities derived from population -based time trade-off values . Results . Using the tobit model , the effect on tariff values was as follows : myocardial infa rct ion = -0.055 ( 95 % confidence interval [ CI ] = -0.067 , -0.042 ) , blindness in 1 eye = -0.074 ( 95 % CI = -0.124 , -0.052 ) , ischemic heart disease = -0.090 ( 95 % CI = -0.126 , -0.054 ) , heart failure = -0.108 ( 95 % CI = -0.169 , -0.048 ) , stroke = -0.164 ( 95 % CI = -0.222 , -0.105 ) , and amputation = -0.280 ( 95 % CI = -0.389 , -0.170 ) . The impact on the VAS scores was smaller , but the ranking was identical . Estimates of these effects , based on the nonparametric CLAD estimator , are also reported and compared . Conclusion . These results demonstrate the magnitude of the impact of 6 complications on utility-based measures of quality of life , which can be used to estimate the outcome of interventions that reduce these diabetes-related complications BACKGROUND Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention ( PCI ) . However , evidence -based guidelines for dosing have not been established for either agent . METHODS We r and omly assigned , in a 2-by-2 factorial design , 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel ( a 600-mg loading dose on day 1 , followed by 150 mg daily for 6 days and 75 mg daily thereafter ) or st and ard-dose clopidogrel ( a 300-mg loading dose and 75 mg daily thereafter ) and either higher-dose aspirin ( 300 to 325 mg daily ) or lower-dose aspirin ( 75 to 100 mg daily ) . The primary outcome was cardiovascular death , myocardial infa rct ion , or stroke at 30 days . RESULTS The primary outcome occurred in 4.2 % of patients assigned to double-dose clopidogrel as compared with 4.4 % assigned to st and ard-dose clopidogrel ( hazard ratio , 0.94 ; 95 % confidence interval [ CI ] , 0.83 to 1.06 ; P=0.30 ) . Major bleeding occurred in 2.5 % of patients in the double-dose group and in 2.0 % in the st and ard-dose group ( hazard ratio , 1.24 ; 95 % CI , 1.05 to 1.46 ; P=0.01 ) . Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI ( 1.6 % vs. 2.3 % ; hazard ratio , 0.68 ; 95 % CI , 0.55 to 0.85 ; P=0.001 ) . There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome ( 4.2 % vs. 4.4 % ; hazard ratio , 0.97 ; 95 % CI , 0.86 to 1.09 ; P=0.61 ) or major bleeding ( 2.3 % vs. 2.3 % ; hazard ratio , 0.99 ; 95 % CI , 0.84 to 1.17 ; P=0.90 ) . CONCLUSIONS In patients with an acute coronary syndrome who were referred for an invasive strategy , there was no significant difference between a 7-day , double-dose clopidogrel regimen and the st and ard-dose regimen , or between higher-dose aspirin and lower-dose aspirin , with respect to the primary outcome of cardiovascular death , myocardial infa rct ion , or stroke . ( Funded by Sanofi-Aventis and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00335452 . OBJECTIVES We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 ( TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infa rct ion ) analysis . BACKGROUND Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention , but it is associated with an increased risk of major bleeding . METHODS L and mark analyses for efficacy , safety , and net clinical benefit were performed from r and omization to day 3 and from day 3 to the end of the trial . RESULTS Significant reductions in ischemic events , including myocardial infa rct ion , stent thrombosis , and urgent target vessel revascularization , were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial . Thrombolysis In Myocardial Infa rct ion major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study . Net clinical benefit significantly favored prasugrel both early and late in the trial . CONCLUSIONS Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events . This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12 ) receptor inhibition , not only for the prevention of periprocedural ischemic events but also during long-term follow-up . The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase . Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose ( e.g. , reduction in maintenance dose in previously reported high-risk subgroups , such as the elderly and those patients with low body weight ) . ( A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention ; NCT00097591 ) OBJECTIVES We evaluated the efficacy and safety of prasugrel and clopidogrel in the setting of a glycoprotein ( GP ) IIb/IIIa inhibitor . BACKGROUND Prasugrel reduced cardiovascular events as compared with clopidogrel in TRITON-TIMI 38 ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infa rct ion 38 ) but with increased bleeding . METHODS Research ers in the TRITON-TIMI 38 r and omized 13,608 subjects with acute coronary syndrome undergoing percutaneous coronary intervention to prasugrel versus clopidogrel . The use of a GP IIb/IIIa inhibitor was at the physician 's discretion . For the current analysis , end points were examined at 30 days and were stratified by use of a GP IIb/IIIa inhibitor . RESULTS A total of 7,414 subjects ( 54.5 % ) received a GP IIb/IIIa inhibitor during their index hospitalization . There was a consistent benefit of prasugrel over clopidogrel for reducing cardiovascular death , myocardial infa rct ion , or stroke in patients who did ( hazard ratio : 0.76 ; 95 % confidence interval : 0.64 to 0.90 ) or did not receive a GP IIb/IIIa inhibitor ( hazard ratio : 0.78 ; 95 % confidence interval : 0.63 to 0.97 , p(interaction ) = 0.83 ) . Prasugrel significantly reduced myocardial infa rct ion , urgent revascularization , and stent thrombosis irrespective of GP IIb/IIIa inhibitor use . Although subjects treated with a GP IIb/IIIa inhibitor had greater rates of bleeding , the risk of Thrombolysis in Myocardial Infa rct ion major or minor bleeding with prasugrel versus clopidogrel was not significantly different in patients who were or were not treated with GP IIb/IIIa inhibitor ( p(interaction ) = 0.19 ) . CONCLUSIONS Prasugrel significantly reduces the risk of cardiovascular events in patients with acute coronary syndromes after percutaneous coronary intervention regardless of whether or not a GP IIb/IIIa inhibitor is used . The use of a GP IIb/IIIa inhibitor does not accentuate the relative risk of bleeding with prasugrel as compared with clopidogrel Background — In patients with acute coronary syndromes and planned percutaneous coronary intervention , the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel – Thrombolysis in Myocardial Infa rct ion 38 ( TRITON-TIMI 38 ) demonstrated that treatment with prasugrel versus clopidogrel was associated with reduced rates of cardiovascular death , MI , or stroke and an increased risk of major bleeding . We evaluated the cost-effectiveness of prasugrel versus clopidogrel from the perspective of the US healthcare system by using data from TRITON-TIMI 38 . Methods and Results — Detailed re source use data were prospect ively collected for all patients recruited from 8 countries ( United States , Australia , Canada , Germany , Italy , Spain , United Kingdom , and France ; n=3373 prasugrel , n=3332 clopidogrel ) . Hospitalization costs were estimated on the basis of diagnosis-related group and in-hospital complications . Cardiovascular medication costs were estimated by using net wholesale prices ( clopidogrel=$4.62/d ; prasugrel=$5.45/d ) . Life expectancy was estimated from in-trial cardiovascular and bleeding events with the use of statistical models of long-term survival from a similar population from the Saskatchewan Health Data base . Over a median follow-up of 14.7 months , average total costs ( including study drug ) were $ 221 per patient lower with prasugrel ( 95 % confidence interval , −759 to 299 ) , largely because of a lower rate of rehospitalization involving percutaneous coronary intervention . Prasugrel was associated with life expectancy gains of 0.102 years ( 95 % confidence interval , 0.030 to 0.180 ) , primarily because of the decreased rate of nonfatal MI . Thus , compared with clopidogrel , prasugrel was an economically dominant treatment strategy . If a hypothetical generic cost for clopidogrel of $ 1/d is used , the incremental net cost with prasugrel was $ 996 per patient , yielding an incremental cost-effectiveness ratio of $ 9727 per life-year gained . Conclusion — Among acute coronary syndrome patients with planned percutaneous coronary intervention , treatment with prasugrel versus clopidogrel for up to 15 months is an economically attractive treatment strategy . Clinical Trial Registration — clinical trials.gov . Unique identifier : NCT00097591 |
11,162 | 26,289,586 | Based on this review , there is insufficient evidence to support or refute the use of TMS to treat symptoms of schizophrenia .
Although some evidence suggests that TMS , and in particular temporoparietal TMS , may improve certain symptoms ( such as auditory hallucinations and positive symptoms of schizophrenia ) compared to sham TMS , the results were not robust enough to be unequivocal across the assessment measures used .
There was insufficient evidence to suggest any added benefit with TMS used as an adjunctive therapy to antipsychotic medication . | BACKGROUND People with schizophrenia often experience symptoms which fail to fully respond to antipsychotic medication .
Transcranial magnetic stimulation ( TMS ) has been proposed as a new treatment for people with schizophrenia , especially those who experience persistent auditory hallucinations .
OBJECTIVES To estimate the effects of TMS alone , compared with sham TMS or with ' st and ard management ' and any other comparison interventions in reducing psychotic symptoms associated with schizophrenia . | BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) has shown promise as a treatment for refractory auditory hallucinations ( AH ) in Schizophrenia . Most previous studies have examined the effect of low frequency , left-sided stimulation ( LFL ) ( 1 Hz ) to the temporoparietal cortex ( TPC ) . Priming stimulation ( 6 Hz ) prior to LFL stimulation ( hereby simply referred to as priming ) has been shown to enhance the neurophysiological effects of LFL rTMS alone and , as such , may lead to greater attenuation of AH . OBJECTIVE Therefore , this study evaluated the efficacy of priming rTMS and LFL rTMS compared to sham rTMS using MRI targeting of Heschl 's gyrus ( HG ) within the TPC of subjects with SCZ experiencing refractory auditory hallucinations ( AH ) . METHODS Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital . Fifty-four subjects with medication resistant AH were r and omized to receive LFL , priming , or sham rTMS for 20 treatments . The primary outcome was reduction of hallucinatory symptoms as indexed by response rates on the Psychotic Symptoms Rating Scale ( PSYRATS ) . RESULTS The response rates did not differ among the three treatment groups using an intention to treat analysis . The response rates did not differ in any of the secondary outcome measures . The treatment was well tolerated with minimal adverse effects including no changes in cognition during the study . CONCLUSION These findings suggest that neither priming nor LFL rTMS of Heschl 's gyrus are effective at ameliorating refractory AH in schizophrenia . Clinical Trials.gov Identifier : NCT01386918 Auditory hallucinations have been associated with a disruption in monitoring one 's own speech suggesting an autonoetic agnosia in schizophrenia . This deficit can be measured by a source monitoring task . Low frequency transcranial magnetic stimulations ( rTMS ) applied to the left temporoparietal cortex can inhibit cortical areas involved both in autonoetic agnosia ( which means ' the inability to identify self-generated mental events ' ) and in auditory hallucinations ( AH ) phenomena . Although improvements in AH have been repeatedly reported following rTMS treatment , effects on autonoetic agnosia measured by source monitoring have never been investigated . We aim ed to investigate the relation between improvements in AH and source monitoring performance after rTMS treatment . Twenty four right-h and ed refractory schizophrenic patients with hallucinations r and omly received sham or active 10.0001-Hz rTMS to the left temporoparietal cortex and performed 2 source monitoring tasks requiring discrimination between silent- and overt-reading words before and after rTMS sessions . Compared to sham , active rTMS significantly improved AH . Source monitoring performances and the improvements tended to correlate , which would support a specific relation between autonoetic agnosia and auditory hallucinations In an open study , four subjects with a stable deficit syndrome of schizophrenia received high frequency repetitive transcranial magnetic stimulation ( 15 Hz at 90 % of motor threshold , 1800 pulses each session , daily for 20 sessions over 4 weeks ) over the left dorsolateral prefrontal cortex . Subjects showed a significant reduction in negative symptoms and improvement in function , with no change in positive symptoms . This improvement was maintained at the 1 month follow up . Repetitive transcranial magnetic stimulation as a treatment of the deficit syndrome of schizophrenia is feasible , safe and may be beneficial . A systematic study in r and omized control trials would be appropriate OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations ( AVH ) , a phenomenon that may relate to activation of brain areas underlying speech perception . Repetitive transcranial magnetic stimulation ( rTMS ) at 1 Hz reduces cortical activation , and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH . The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit . METHODS Ten right-h and ed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS ( 2,000 stimulations per day at 90 % of motor threshold ) over the left temporoparietal cortex in a double-blind crossover design . The two weeks of stimulation were separated by a 1-week washout period . RESULTS AVH were robustly improved ( 56 % ) by 5 days active rTMS , whereas no variation was observed after sham . Seven patients were responders to active treatment , five of whom maintained improvement for at least 2 months . CONCLUSIONS These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex , compared with sham stimulation , in reducing resistant AVH . This improvement can be obtained in only 5 days without serious initial adverse events Background About 25 % of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy . We conducted a deep transcranial magnetic stimulation ( TMS ) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients . The results were encouraging , but a sham-controlled study was needed to rule out a placebo effect . Methods A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited , from Beer Yaakov MHC and other hospitals outpatient population s. Patients received 10 daily treatment sessions with low-frequency ( 1 Hz for 10 min ) deep TMS applied over the left temporoparietal cortex , using the H1 coil at the intensity of 110 % of the motor threshold . Procedure was either real or sham according to patient r and omization . Patients were evaluated via the Auditory Hallucinations Rating Scale , Scale for the Assessment of Positive Symptoms-Negative Symptoms , Clinical Global Impressions , and Quality of Life Question naire . Results In all , 10 patients completed the treatment ( 10 TMS sessions ) . Auditory hallucination scores of both groups improved ; however , there was no statistical difference in any of the scales between the active and the sham treated groups . Conclusions Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients .Trial Registration Clinical trials.gov identifier : NCT00564096 BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) has been investigated for its treatment efficacy for the negative symptoms of schizophrenia . Previous studies have targeted the dorsolateral prefrontal cortex ( DLPFC ) , which is associated with the pathophysiology of this disorder . Several rTMS parameters have been explored in the treatment of negative symptoms and include stimulating the left and bilateral DLPFC at several different frequencies and number of sessions . Results of such studies have been inconsistent , while high-frequency rTMS has shown greatest promise . OBJECTIVE /HYPOTHESIS The objective of this study was to evaluate the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms in schizophrenia . It was hypothesized rTMS would alleviate negative symptoms in schizophrenia . METHODS Twenty-five patients were enrolled in this double-blind placebo-controlled r and omized trial . Bilateral 20 Hz rTMS was MRI-targeted to the DLPFC at 90 % RMT administered daily for 4 weeks for a total of 20 treatments . Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms ( SANS ) , the Positive and Negative symptom scale ( PANSS ) , and controlling for depression as measured with the Calgary Depression Scale ( CDS ) at baseline , 1 , 2 , 3 , 4 , and 2 weeks after the treatment course . RESULTS No significant group or time differences were found on negative symptoms or depressive symptoms after rTMS . Bilateral high-frequency rTMS did not alleviate negative symptoms in patients with schizophrenia . CONCLUSIONS These findings indicate that such symptoms are unresponsive to rTMS treatment or that more optimized parameters are needed to achieve improved therapeutic efficacy Background : Previous research suggests that repetitive transcranial magnetic stimulation ( rTMS ) applied to the temporoparietal cortex may have therapeutic benefits for patients with schizophrenia and treatment-resistant auditory hallucinations . We aim ed to test this hypothesis in a r and omized double-blind trial . Methods : Thirty-three patients with treatment-resistant auditory hallucinations entered a r and omized sham-controlled , double-blind trial . rTMS was applied for 10 consecutive weekdays , for 15 minutes at 1 Hz and 90 % of the resting motor threshold . We assessed clinical symptoms and cognitive function . Results : rTMS was safe with no adverse effects on memory and cognitive parameters assessed . Active treatment did not result in a greater therapeutic effect than sham on any measure except for the loudness of hallucinations where there was a significant reduction in the active versus the sham group over time . Conclusions : The study does not support the effectiveness of rTMS using the stimulation parameters provided . However , it does suggest that rTMS methods may have a therapeutic role and indicates the need for further exploration of alternative and more effective stimulation methods Objective : Auditory hallucinations are a characteristic symptom of schizophrenia and are usually resistant to treatment . The present study was conducted to further support the findings that repetitive transcranial magnetic stimulation ( rTMS ) reduces auditory hallucinations , and to evaluate the effect of low-frequency rTMS on auditory hallucinations in schizophrenia . Methods : Forty schizophrenia patients were included in the study . Patients were r and omized to control or experimental group . Low-frequency rTMS ( 1 Hz , 90 % motor threshold ) was applied to the left temporoparietal cortex of patients in the experimental group for 10 days following the st and ard guidelines as an addition to antipsychotic treatment . The control group received only antipsychotics . The changes in the psychopathology scores for the auditory hallucinations were recorded using auditory hallucination recording scale . The rater was blind to the intervention procedure . Results : A significant improvement was found in auditory hallucinations in the experimental group as compared to the control group . Conclusion : Left temporoparietal rTMS warrants further study as an intervention for auditory hallucinations . Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations Summary .The effects of repetitive transcranial magnetic stimulation ( rTMS ) on schizophrenic negative symptoms ( NS ) and EEG topography were investigated in this pilot study .10 patients with predominant NS were treated with 10 Hz rTMS over the left dorsolateral prefrontal cortex for 5 days . For NS ratings , the Scale for the Assessment of Negative Symptoms ( SANS ) was used . Both ratings and EEG recordings were obtained pre- and post-rTMS . Electrical activity changes were computed by Low Resolution Brain Electromagnetic Tomography . SANS showed an improvement after rTMS , from 49.0 ( SD : 10.7 ) to 44.7 ( SD : 11.8 ) ( means ) . EEG frequency b and s were changed fronto-temporally ( right ) and were mainly decreases in delta- and beta- and increases in alpha1-activity , as well as decreases in beta-activity in the temporal and parieto-occipital regions (left).Although we are aware of the limitations of this study , we assume a slight improvement in NS . The EEG findings refer to a possible neurophysiologic correlate of their improvement after rTMS Schizophrenia is a complex and heterogeneous psychiatric disorder . Auditory verbal hallucinations occur in 50 - 70 % of patients with schizophrenia and are associated with significant distress , decreased quality of life and impaired social functioning . This study aim ed to investigate the effects of active compared with sham 1-Hz repetitive transcranial magnetic stimulation ( rTMS ) applied to the left temporal-parietal cortex in patients with schizophrenia treated with clozapine . Symptom dimensions that were evaluated included general psychopathology , severity of auditory hallucinations , quality of life and functionality . Seventeen right-h and ed patients with refractory schizophrenia experiencing auditory verbal hallucinations and treated with clozapine were r and omly allocated to receive either active rTMS or sham stimulation . A total of 384 min of rTMS was administered over 20 days using a double-masked , sham-controlled , parallel design . There was a significant reduction in Brief Psychiatric Rating Scale ( BPRS ) scores in the active group compared with the sham group . There was no significant difference between active and sham rTMS on Quality of Life Scale ( QLS ) , Auditory Hallucinations Rating Scale ( AHRS ) , Clinical Global Impressions ( CGI ) and functional assessment staging ( FAST ) scores . Compared with sham stimulation , active rTMS of the left temporoparietal cortex in clozapine-treated patients showed a positive effect on general psychopathology . However , there was no effect on refractory auditory hallucinations . Further studies with larger sample sizes are needed to confirm these findings BACKGROUND Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied to the left temporoparietal area ( TP ) has been investigated as a treatment method for auditory verbal hallucinations ( AVH ) yielding inconsistent results . In vitro studies have indicated that the effects of low-frequency rTMS can be enhanced by a brief pretreatment phase consisting of high-frequency rTMS ( i.e. , priming rTMS ) . OBJECTIVE The aim of this single-blind , r and omized controlled study was to investigate whether the effects of rTMS on AVH can be enhanced with priming rTMS . METHODS Twenty-three patients with medication-resistant AVH were r and omized over two groups : one receiving low-frequency rTMS preceded by 5 minutes of 6 Hertz rTMS ; and another receiving low-frequency rTMS without priming . Both treatments were directed at the left TP . The total duration of stimulation was equal in the two groups , namely , 15 sessions of 20 minutes each . The severity of AVH and other psychotic features were measured with the aid of the Auditory Hallucination Rating Scale ( AHRS ) , the Positive and Negative Syndrome Scale ( PANSS ) and the Psychotic Symptom Rating Scales ( PSYRATS ) . RESULTS The severity of AVH and other psychotic symptoms in the group with priming was not significantly lower after 3 weeks of treatment in comparison to baseline . The group treated with st and ard rTMS showed a trend toward improvement after 3 weeks of treatment . No significant differences were observed on any of the rating scales between the group with and without priming . CONCLUSIONS This study does not provide evidence that priming rTMS is an effective treatment for AVH The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas BACKGROUND The aim of this study was to extend our previous work on the therapeutic efficacy of repetitive transcranial magnetic stimulation ( rTMS ) in major depression to patients with schizophrenia . METHODS Thirty-five in patients with schizophrenia were r and omly assigned to either right prefrontal rTMS or sham treatment and were rated before and after treatment for positive , negative , and depressive symptoms . RESULTS Thirty-one subjects ( rTMS = 16 , sham = 15 ) completed a 2-week treatment protocol . No serious adverse effects were reported ; however , rTMS was not superior to sham treatment on any of the clinical ratings . CONCLUSIONS In contrast to our previous positive findings in major depression , right prefrontal slow rTMS does not appear to have a beneficial effect for actively psychotic patients with schizophrenia BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) is increasingly being investigated as a potential treatment for a number of psychiatric disorders , including schizophrenia . Previous rTMS studies have targeted the left-side prefrontal cortex ( PFC ) in the treatment of negative symptoms , with inconsistent findings . Some imaging evidence suggests right-sided or bilateral PFC involvement in negative symptoms , areas yet to be investigated for rTMS treatment . The study therefore aim ed to assess the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms . METHODS A 2-arm double-blind r and omized controlled trial was conducted with 20 patients with a diagnosis of schizophrenia or schizoaffective disorder , and moderate-to-severe treatment-resistant negative symptoms . Participants received a 3-week course of high-frequency bilateral rTMS or sham . Twenty trains ( 5 seconds duration ) of 10 Hz rTMS at 110 % of the RMT were administered to each PFC daily , 5 days a week . RESULTS No significant group or time differences in the Scale for the Assessment of Negative Symptoms ( SANS ) scores or cognitive outcomes were evident . However , a trend for greater reduction in scores on the autistic preoccupation scale of the Positive and Negative Symptom Scale for the active group compared to the sham group was observed ( P = .05 ) . CONCLUSIONS No substantial benefit of high-frequency bilateral rTMS was seen in the treatment of the negative symptoms of schizophrenia . Further research is required to explore whether rTMS may have benefits specific to particular cognitive or symptom domains The aim of this study was to evaluate the effect of repetitive transcranial magnetic stimulation ( rTMS ) on the left and right temporoparietal cortex compared with sham stimulation in schizophrenic patients with treatment-refractory auditory hallucinations ( AH ) . Thirty-nine patients with schizophrenia with treatment-refractory AH were allocated r and omly to one of three groups : daily left , right , and sham rTMS groups . rTMS was applied to the TP3 or 4 regions with the aid of the electroencephalography 10 - 20 international system at 1 Hz for 20 min per day for 10 treatment days . Symptoms were evaluated using the Auditory Hallucination Rating Scale ( AHRS ) , the Positive and Negative Symptoms Scale ( PANSS ) , the Clinical Global Impression -- Severity ( CGI-S ) , and Clinical Global Impression -- Improvement ( CGI-I ) scale . For the time effect ( within-subject comparison ) , there were significant changes in the frequency of AHs , positive symptoms of PANSS , and CGI-I. A between-group comparison revealed significant differences in the positive symptoms of PANSS , and CGI-I scores . Post hoc analysis revealed that both the right- and left-side rTMS treatment groups exhibited better CGI-I scores compared to the sham-stimulated group . This study suggests that 10 days of low-frequency rTMS applied daily for 20 min to either temporoparietal cortex significantly reduces the symptoms in patients with schizophrenia who are having refractory AH , but the left sided rTMS is not superior to right or sham rTMS In a double-blind , controlled study , we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation ( rTMS ) on schizophrenia symptoms . A total of 22 chronic hospitalized schizophrenia patients were r and omly assigned to 2 weeks ( 10 sessions ) of real or sham rTMS . rTMS was given with the following parameters : 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold , 30 seconds apart . Effects on positive and negative symptoms , self-reported symptoms , rough neuropsychological functioning , and hormones were assessed . Although there was a significant improvement in both groups in most of the symptom measures , no real differences were found between the groups . A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group . There was no change in hormone levels or neuropsychological functioning , measured by the MMSE , in either group . Left prefrontal rTMS ( with the used parameters ) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients BACKGROUND Auditory hallucinations are often resistant to treatment and can produce significant distress and behavioral difficulties . A preliminary report based on 24 patients with schizophrenia or schizoaffective disorder indicated greater improvement in auditory hallucinations following 1-hertz left temporoparietal repetitive transcranial magnetic stimulation ( rTMS ) compared to sham stimulation . Data from the full 50-subject sample incorporating 26 new patients are now presented to more comprehensively assess safety/tolerability , efficacy and moderators of this intervention . METHODS Right-h and ed patients experiencing auditory hallucinations at least 5 times per day were r and omly allocated to receive either rTMS or sham stimulation . A total of 132 minutes of rTMS was administered over 9 days at 90 % motor threshold using a double-masked , sham-controlled , parallel design . RESULTS Hallucination Change Score was more improved for rTMS relative to sham stimulation ( p = .008 ) as was the Clinical Global Impressions Scale ( p = .0004 ) . Hallucination frequency was significantly decreased during rTMS relative to sham stimulation ( p = .0014 ) and was a moderator of rTMS effects ( p = .008 ) . There was no evidence of neurocognitive impairment associated with rTMS . CONCLUSIONS Left temporoparietal 1-hertz rTMS warrants further study as an intervention for auditory hallucinations . Data suggest that this intervention selectively alters neurobiological factors determining frequency of these hallucinations INTRODUCTION The purpose of this study was to assess tolerability and safety of high-frequency rTMS with regard to cognitive performance when conducted as " add-on " treatment in chronic schizophrenia in- patients ( n=32 ) . METHODS Patients , who were on stable antipsychotic treatment , were r and omly assigned to verum or sham condition ( double-blind ) . In the verum group , ten sessions of 10 Hz rTMS with a total of 10 000 stimuli were applied over the left dorsolateral prefrontal cortex ( PFC ) at 110 % of motor threshold over a period of two weeks . The sham group received corresponding sham stimulation . RTMS effects on cognitive performance were assessed with a neuropsychological test battery consisting of the following tests : trail making test A and B ( TMT ) , Wisconsin card sorting test ( WCST ) , D2 attention task and the " short test of general intelligence " ( KAI ) . RESULTS No statistically significant deterioration of cognitive performance was observed as a result of rTMS treatment . Moreover it was shown that in the verum group patients with a less favourable performance on the WCST at baseline tend to improve after rTMS treatment with regard to psychopathology as opposed to patients in the control group . DISCUSSION The stability of cognitive function suggests good tolerability of rTMS treatment in schizophrenia . The absence of evidence for cognitive deterioration could be due to low and short stimulation parameters BACKGROUND Schizophrenia is a disabling disease with a significant proportion of patients experiencing persistent symptoms . Repetitive transcranial magnetic stimulation ( rTMS ) is a promising new therapeutic tool that could benefit to schizophrenic patients . In this study we sought to assess the efficacy of active rTMS compared to sham stimulation in the treatment of patients with schizophrenia . METHOD Eighteen schizophrenic patients according to DSM-IV criteria were r and omly allocated to receive active or sham rTMS for 10 days over the left temporoparietal cortex ( 80 % of the motor threshold , 1Hz , five trains of 1 min ) . Psychopathological dimensions were measured with the positive and negative syndrome scale and clinical global impression at baseline and after 10 session of rTMS . RESULTS All patients were improved at the end of the trial but no significant group differences were found . Patients receiving sham stimulation showed the same pattern of improvement compared to active condition on all the subscales of the positive and negative syndrome scale and clinical global impression scores ( p>0.05 ) . CONCLUSION In our study , active rTMS failed to show superiority over sham stimulation in the treatment of schizophrenic symptoms . Although previous results have shown that rTMS reduces auditory hallucination , its efficacy on other positive schizophrenic symptoms is not yet established . Nevertheless , the results of our study , even though negative , provide further insights in the pathophysiology of schizophrenia BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) of frontal brain regions is under study as a non-invasive method in the treatment of affective disorders . Recent publications provide increasing evidence that rTMS may be useful in treating schizophrenia . Results are most intriguing , demonstrating a reduction of negative symptoms following high-frequency rTMS . In this context , disentangling of negative and depressive symptoms is of the utmost importance when underst and ing specific rTMS effects on schizophrenic symptoms . METHOD Using a sham-controlled parallel design , 20 patients with schizophrenia were included in the study . Patients were treated with high-frequency 10 Hz rTMS over 10 days . Besides clinical ratings , ECD-SPECT ( technetium-99 bicisate single photon emission computed tomography ) imaging was performed before and after termination of rTMS treatment . RESULTS High-frequency rTMS leads to a significant reduction of negative symptoms combined with a trend for non-significant improvement of depressive symptoms in the active stimulated group as compared with the sham stimulated group . Additionally , a trend for worsening of positive symptoms was observed in the actively treated schizophrenic patients . In both groups no changes in regional cerebral blood flow could be detected by ECD-SPECT . CONCLUSIONS Beneficial effects of high-frequency rTMS on negative and depressive symptoms were found , together with a trend for worsening positive symptoms in schizophrenic patients BACKGROUND Neuroimaging studies suggest that auditory hallucinations ( AHs ) of speech arise , at least in part , from activation of brain areas underlying speech perception . One-hertz repetitive transcranial magnetic stimulation ( rTMS ) produces sustained reductions in cortical activation . Recent results of 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs . We sought to determine if a more extended trial of rTMS could significantly reduce AHs that were resistant to antipsychotic medication . METHODS Twenty-four patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were r and omly allocated to receive rTMS or sham stimulation for 9 days at 90 % of motor threshold . Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS . Neuropsychological assessment s were administered at baseline and during and following each arm of the trial . RESULTS Auditory hallucinations were robustly improved with rTMS relative to sham stimulation . Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement . Duration of putative treatment effects ranged widely , with 52 % of patients maintaining improvement for at least 15 weeks . Repetitive transcranial magnetic stimulation was well tolerated , without evidence of neuropsychological impairment . CONCLUSIONS These data suggest that the mechanism of AHs involves activation of the left temporoparietal cortex . One-hertz rTMS deserves additional study as a possible treatment for this syndrome OBJECTIVE To study the therapeutic effects on auditory hallucinations refractory to clozapine with 1-Hz repetitive transcranial magnetic stimulation ( rTMS ) applied on the left temporoparietal cortex . METHOD Eleven patients with schizophrenia ( DSM-IV ) experiencing auditory hallucinations ( unresponsive to clozapine ) were r and omly assigned to receive either active of rTMS ( N = 6 ) or sham stimulation ( N = 5 ) ( with concomitant use of clozapine ) using a double-masked , sham-controlled , parallel design . A total of 160 minutes of rTMS ( 9600 pulses ) was administered over 10 days at 90 % motor threshold . The study was conducted from January 2003 to December 2005 . RESULTS There was a reduction in hallucination scores in both groups , which persisted during follow-up in the active group for the items reality ( p = .0493 ) and attentional salience ( p = .0360 ) . Both groups showed similar patterns of symptomatic changes on subscales ( negative symptoms , general psychopathology ) and total scores of the Positive and Negative Syndrome Scale , Clinical Global Impressions scale , and Visual Analog Scale . CONCLUSION Active rTMS in association with clozapine can be administered safely to treat auditory hallucinations , although its clinical utility is still question able . No significant clinical effects were observed in the sample studied , possibly because it was too small and /or due to its high refractoriness BACKGROUND Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication . Using repetitive transcranial magnetic stimulation ( rTMS ) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms . METHODS We performed a double-blind r and omized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia . 17 right-h and ed patients with prominent negative symptoms ( PANSS negative subscore > or=20 ) were r and omized to a 10 day course of real ( n=8 ) or sham rTMS ( n=9 ) applied to the left dorsolateral prefrontal cortex ( 20 trains per day , 10 s treatment at 10 Hz , 50 s inter-train interval , 110 % of motor threshold ) . The primary outcome measure was PANSS negative symptom score . Secondary outcomes included mood , cognitive function and side-effects . Patients were followed-up two weeks afterwards . The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA . RESULTS All subjects completed the treatment course . There was no significant difference between the two groups on PANSS negative symptom scores at either time point . At the end of treatment , no subjects in either group met the criterion for response ( i.e. a 20 % reduction in baseline PANSS negative symptom score ) . The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up . CONCLUSIONS Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up Repetitive transcranial magnetic stimulation ( rTMS ) can be beneficial in schizophrenia , possibly through a reversal of pre-treatment hypofrontality . Twelve schizophrenic patients ( 8 men , 4 women ) were treated with high-frequency rTMS of the dominant dorsolateral prefrontal cortex . Their performance of the number-connection test , which assesses cognitive processes related to the frontal lobe , was evaluated before and after rTMS . Women improved markedly on the test after rTMS , whereas men did not show a significant change . There were no corresponding sex differences in clinical measures after rTMS . The preliminary findings of sex differences in the response to rTMS , as reflected by performance on the number-connection test , suggest the need for investigations of a greater number of schizophrenic men and women with a more intensive examination of the effects of rTMS on cognitive functions Background : In a previous functional magnetic resonance imaging study , the authors succeeded in demonstrating the activation of Heschl ’s gyrus during auditory hallucinations ( AH ) . Objectives : This study aims to treat AH specifically by repetitive transcranial magnetic stimulation ( rTMS ) . Methods : 16 patients with AH were included in a r and omized , cross-over , sham-controlled trial . 1 Hz rTMS was administered over the left and right temporo-parietal cortex and sham position , respectively , on 5 consecutive days ; 900 stimuli each , strength 100 % of motor threshold . Using the Psychotic Symptom Rating Scales ( PSYRATS ) , the hallucinations during the stimulation periods and 4-week follow-ups were quantified . Electroencephalograms ( EEG ) were acquired before and after each period . Results : Treatment responses were observed after left hemisphere rTMS only . The 5 patients who showed a response did so already after 2 days . However , group mean hallucination scores did not differ across treatment conditions . No significant changes were found in EEG after rTMS . Conclusions : A subgroup of patients suffering from AH benefits soon after treatment start from rTMS over the left superior temporal gyrus as revealed by the decrease of AH scores compared to right-sided and sham procedures UNLABELLED We conducted a r and omized , sham-controlled repetitive transcranial magnetic stimulation ( rTMS ) study in chronic schizophrenia in- patients ( n=35 ) to evaluate the therapeutic efficacy of 10 Hz stimulation . Patients , who were on stable antipsychotic treatment , were r and omly assigned to the active or sham condition . In the active rTMS group , ten sessions with a total of 10,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110 % of motor threshold . The sham group received corresponding sham stimulation . Clinical improvement was measured by the Clinical Global Impression scale ( primary outcome measure ) , the Global Assessment of Functioning Scale ( GAF ) and the Positive and Negative Symptom Scale ( PANSS ; secondary outcome measures ) . Between-group comparisons revealed no significant differences in clinical outcome variables . Only a subgroup of patients with pronounced negative symptoms developed some clinical improvement as indicated by significant changes in the GAF-scale . Besides there is some evidence for a more favourable clinical outcome within this subgroup after rTMS in the CGI-S and PANSS negative scale , too . In line with earlier investigations , our results suggest a moderate - potentially clinical ly relevant - treatment effect of prefrontal 10 Hz rTMS stimulation in chronic patients . However , in our study this beneficial effect was restricted to subjects with pronounced negative symptoms . CLINICAL TRIAL REGISTRATION INFORMATION Clinical Trial.gov Identifier : NCT00169689 , http://www . clinical trials.gov OBJECTIVE To evaluate the effect of different paradigms of repetitive transcranial magnetic stimulation ( rTMS ) on the treatment of schizophrenia through assessing cognitive function and psychotic symptoms . METHODS Eighty patients diagnosed with schizophrenia were r and omly assigned to four groups , which were sham intervention group , theta burst stimulation ( TBS ) group , 10 Hz group and 20 Hz group . All the subjects were exposed to 5 daily treatments at 80 % of motor threshold over the left dorsolateral prefrontal cortex with a total stimuli of 1 200 per day , while being maintained on their former antipsychotic treatment . Visual spatial working memory test and verbal fluency test were applied to evaluate the cognitive function , while Positive and Negative Symptom Scale ( PANSS ) was used to assess the psychotic symptoms . RESULTS 20 Hz of rTMS could improve the visual spatial working memory of schizophrenia patients ( t=-2.469,P=0.024 ) . Only patients in TBS group showed significant improvement of verbal fluency test after rTMS treatment ( t=-4.538,P=0.000 ) . The negative symptoms were alleviated significantly both in TBS and 10 Hz groups ( TBS : t=5.373,P=0.000 ; 10 Hz : t=2.272,P=0.036 ) . General psychopathology symptoms were improved significantly both in 10 Hz and 20 Hz groups ( 10 Hz : t=2.725,P=0.014;20 Hz : t=3.632,P=0.002 ) . CONCLUSION The effects of rTMS on the cognitive function and psychotic symptoms of schizophrenia vary according to the changes in stimulus parameters , suggesting that rTMS could provide a new way for the individual therapy of schizophrenia BACKGROUND Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments . Repetitive transcranial magnetic stimulation ( rTMS ) targeted over the dorsolateral prefrontal cortex has been shown to modulate neurophysiological mechanisms linked to working memory in schizophrenia and improves working memory performance in healthy subjects and might therefore represent a treatment modality for schizophrenia patients . The objectives were to evaluate the effects of rTMS on working memory performance in schizophrenia patients and evaluate whether rTMS normalizes performance to healthy subject levels . METHODS In a 4-week r and omized double-blind sham-controlled pilot study design , 27 medicated schizophrenia patients were tested at the Centre for Addiction and Mental Health ( a university teaching hospital that provides psychiatric care to a large urban catchment area and serves as a tertiary referral center for the province of Ontario ) . Patients performed the verbal working memory n-back task before and after rTMS magnetic resonance image targeted bilaterally sequentially to left and right dorsolateral prefrontal cortex 750 pulses/side at 20 Hz for 20 treatments . The main outcome measure was mean magnitude of change in the n-back accuracy for target responses with active ( n = 13 ) or sham ( n = 12 ) rTMS treatment course . RESULTS The rTMS significantly improved 3-back accuracy for targets compared with placebo sham ( Cohen 's d = .92 ) . The improvement in 3-back accuracy was also found to be at a level comparable to healthy subjects . CONCLUSIONS These pilot data suggest that bilateral rTMS might be a novel , efficacious , and safe treatment for working memory deficits in patients with schizophrenia In schizophrenia patients negative symptoms and cognitive impairment often persist despite treatment with second generation antipsychotics leading to reduced quality of life and psychosocial functioning . One core cognitive deficit is impaired working memory ( WM ) suggesting malfunctioning of the dorsolateral prefrontal cortex . High frequency repetitive transcranial magnetic stimulation ( rTMS ) has been used to transiently facilitate or consoli date neuronal processes . Pilot studies using rTMS have demonstrated improvement of psychopathology in other psychiatric disorders , but a systematic investigation of working memory effects outlasting the stimulation procedure has not been performed so far . The aim of our study was to explore the effect of a 3-week high frequency active or sham 10 Hz rTMS on cognition , specifically on working memory , in schizophrenia patients ( n=25 ) in addition to antipsychotic therapy and in healthy controls ( n=22 ) . We used functional magnetic resonance imaging ( fMRI ) to compare activation patterns during verbal WM ( letter 2-back task ) before and after 3-weeks treatment with rTMS . Additionally , other cognitive tasks were conducted . 10 Hz rTMS was applied over the left posterior middle frontal gyrus ( EEG electrode location F3 ) with an intensity of 110 % of the individual resting motor threshold ( RMT ) over a total of 15 sessions . Participants recruited the common fronto- parietal and subcortical WM network . Multiple regression analyses revealed no significant activation differences over time in any contrast or sample . According to the ANOVAs for repeated measures performance remained without alterations in all groups . This is the first fMRI study that has systematic ally investigated this topic within a r and omized , placebo-controlled , double-blind design , contrasting the effects in schizophrenia patients and healthy controls OBJECTIVE To verify whether high-frequency rTMS applied above the area of the left prefrontal cortex in 15 stimulation sessions with maximum stimulation intensity is able to modify negative symptoms of schizophrenia in a double-blind , r and omized controlled study . METHODS Twenty-two patients with schizophrenia stabilized on antipsychotic medication with prominent negative symptoms were included in the trial . They were divided into two groups : eleven were treated with effective rTMS and eleven with ineffective " sham " rTMS . The ineffectiveness of the sham rTMS was achieved through the stimulation coil position . Stimulation was applied to the left dorsolateral prefrontal cortex . The stimulation frequency was 10 Hz . Stimulation intensity was 110 % of the motor threshold intensity . Each patient received 15 rTMS sessions on 15 consecutive working days . Each daily session consisted of 15 applications of 10-second duration and 30-second intervals between sequences . There were 1500 stimuli per session . RESULTS During real rTMS treatment a statistically significant decrease of negative symptoms was found ( approximately 29 % reduction in the PANSS negative symptom subscale and 50 % reduction in the SANS ) . No adverse events occurred during therapy except for a mild headaches . In sham rTMS treatment a decrease of negative symptoms was also identified , but to a lesser extent than in real rTMS ( about 7 % in negative subscale PANSS and 13 % in SANS ) . The change in SANS achieved statistical significance . Mutual comparison revealed a greater decrease of negative symptoms in favor of real rTMS in contrast to sham rTMS . CONCLUSION The augmentation of rTMS enabled patients to experience a significant decrease in the severity of the negative symptoms . Our results support the therapeutic potential of rTMS at higher frequency for negative symptoms of schizophrenia Auditory-verbal hallucinations are a hallmark symptom of schizophrenia . In recent years , repetitive transcranial magnetic stimulation ( rTMS ) targeting speech perception areas has been advanced as a potential treatment of medication-resistant hallucinations . However , the underlying neural processes remain unclear . This study aim ed to assess whether 1 Hz rTMS treatment would affect functional connectivity of the temporo-parietal junction ( TPJ ) . Resting state fMRI scans were obtained from 18 patients with schizophrenia . Patients were assessed before and after a 6 day treatment with 1 Hz rTMS to the left TPJ , or placebo treatment with sham rTMS to the same location . We assessed functional connectivity between a priori defined regions-of-interest ( ROIs ) comprising the putative AVH network and the bilateral TPJ seed regions , targeted with rTMS . Symptom improvement following rTMS treatment was observed in the left rTMS group , whereas no change at occurred in the placebo group . Although no corresponding changes were observed in the functional connections previously found to be associated with AVH severity , an increase in connectivity between the left TPJ and the right insula was observed in group receiving rTMS to the left TPJ . The placebo group conversely showed a decrease in connectivity between the left TPJ and left anterior cingulate . We conclude that application of 1 Hz rTMS to the left TPJ region may affect functional connectivity of the targeted region . However , the relationship between these functional changes during the resting state and the rate of clinical improvement needs further clarification It has been suggested that low frequency transcranial magnetic stimulation ( TMS ) over left temporo-parietal cortex may reduce the frequency and intensity of auditory hallucinations in schizophrenia . Sixteen patients with hallucinations , treatment-resistant for at least 2 months , were r and omised into a placebo-controlled crossover study of TMS at 1 Hz and 80 % of motor threshold over left temporo-parietal cortex . Treatment periods lasted for 4 days , with daily duration escalating from 4 to 8 , 12 and 16 min on subsequent days . Each minute of stimulation was followed by 15 s of rest to check coil position and allow the patient to move , if necessary . Both patients and symptom raters were unaware of the treatment condition . Patients ' hallucination scores improved from baseline with both real and sham TMS , and there was no significant difference between real and sham treatments . There was a trend for second treatments , whether sham or real , to be more effective than first treatments . Other psychopathology scales ( apart from positive symptoms ) and verbal memory were not affected by real or sham TMS . Previous positive studies could not be replicated with these parameters . TMS is safe if applied within the protocol used Current meta- analysis revealed small , but significant effects of repetitive transcranial magnetic stimulation ( rTMS ) on negative symptoms in patients with schizophrenia . There is a need for further controlled , multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients . The objective of this multicenter , r and omized , sham-controlled , rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy , 15 sessions per 3 weeks , 1,000 stimuli per session , stimulation intensity 110 % of the individual motor threshold ) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia , and to evaluate the effect during a 12 weeks of follow-up . The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score ( PANSS ) . A sample size of 63 in each group will have 80 % power to detect an effect size of 0.50 . Data analysis will be based on the intention to treat population . The study will be conducted at three university hospitals in Germany . This study will provide information about the efficacy of rTMS in the treatment of negative symptoms . In addition to psychopathology , other outcome measures such as neurocognition , social functioning , quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia . Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding BACKGROUND Neuroimaging findings implicate bilateral superior temporal regions in the genesis of auditory-verbal hallucinations ( AVH ) . This study aim ed to investigate whether 1 Hz repetitive transcranial magnetic stimulation ( rTMS ) of the bilateral temporo-parietal region would lead to increased effectiveness in the management of AVH , compared to left rTMS or placebo . METHODS 38 patients with schizophrenia ( DSM-IV ) and medication-resistant AVH were r and omly assigned to 1 Hz rTMS treatment of the left temporo-parietal region , bilateral temporo-parietal regions , or placebo . Stimulation was conducted over 6 days , twice daily for 20 min , at 90 % of the motor threshold . Effect measures included the Auditory Hallucination Rating Scale ( AHRS ) , Positive and Negative Affect Scale ( PANAS ) , and a score for hallucination severity obtained from the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS All groups showed some improvement on the total AHRS . Hallucination frequency was significantly reduced in the left rTMS group only . The bilateral rTMS group demonstrated the most remarkable reduction in self-reported affective responsiveness to AVH . A modest , but significant decrease on the PANSS hallucination item was observed in the combined rTMS treatment group , whereas no change occurred in the placebo group . The left rTMS group showed a significant reduction on the general psychopathology subscale . CONCLUSION Compared to bilateral or sham stimulation , rTMS of the left temporo-parietal region appears most effective in reducing auditory hallucinations , and additionally may have an effect on general psychopathology . Placebo effects should however not be ruled out , since sham stimulation also led to improvement on a number of AVH parameters BACKGROUND Alpha EEG guided Transcranial Magnetic Stimulation ( αTMS ) of the dorsolateral prefrontal cortex ( DLPFC ) has shown promising efficacy for treating the negative symptoms of schizophrenia . OBJECTIVE / HYPOTHESIS : The purpose of the current investigation was to test ( 1 ) the therapeutic effect in other domains of symptoms of schizophrenia and ( 2 ) the specificity of stimulus location . The hypothesis to be tested was that global alpha EEG normalization after αTMS would help improve the clinical symptoms of schizophrenia , regardless of the site of stimulation . METHOD Seventy-eight patients with schizophrenia were enrolled in a r and omized , double-blind , sham-controlled study with four study groups : frontal αTMS , parietal αTMS , frontal sham , and parietal sham . Patients received daily treatment for 10 days and clinical evaluations at day 5 and 10 . The stimulus rate and intensity were determined by individual 's characteristic alpha frequency and motor threshold ( 80 % ) . RESULTS Positive and general psychotic symptoms improved significantly after αTMS ( P < 0.02 ) . Frontal and parietal αTMS had similar effects ( P = 0.48 ) . ( 3 ) αTMS with concomitant typical neuroleptics treatment had greater efficacy than atypical neuroleptics ( P < 0.04 ) . Degree of EEG normalization as measured by increase in Q factor was highly associated with the improvement in all three domains of symptoms of schizophrenia ( P < 0.04 ) . CONCLUSIONS Alpha EEG normalization after treatment with αTMS may directly subserve the processes underlying clinical improvements in schizophrenia . Nonetheless , given the confound of possible unblinding of participants because of an inactive sham control , the current results should be considered preliminary until replicated further Patient reports of systemic side effects and cognitive impairment were obtained the afternoon of each treatment during the electroconvulsive therapy ( ECT ) course . Side effects were grouped a priori as reflecting physical complaints , perceived cognitive impairment , and as mood-related . Patients r and omly assigned to bilateral ECT reported more cognitive impairment than patients who received right unilateral ECT . There were indications that the unilateral ECT group had greater physical/somatic complaints . Patients who responded to ECT differed from nonresponders only on the more explicitly mood-related items . Generally , the findings supported the desirability of extending studies of patient reports of ECT adverse effects to include subjective systemic side effects in addition to subjective cognitive impairment Auditory verbal hallucinations in schizophrenia may be due to dysfunctional inner speech-related cortical areas . Repetitive transcranial magnetic stimulation ( rTMS ) has been reported to be an effective treatment of hallucinations . In a cross-over sham controlled study , we guided rTMS stereotactically to inner speech-related cortical areas in hallucinating patients . These areas were identified individually prior to rTMS using fMRI in a subgroup of our patients . Active stimulation was applied over Broca 's area and over the superior temporal gyrus as determined by fMRI , or according to structural images in the remaining patients . rTMS did not lead to a significant reduction of hallucination severity . Conclusively , rTMS has to be regarded critically as a possible novel tool for the treatment of hallucinations BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials Auditory hallucinations are experienced by 60 - 80 % of person with schizophrenia and can often cause significant distress behavioural dyscontrol . The application of rTMS in the left temporoparietal cortex could modulate the neuronal activation and reduce the occurrence of auditory disperceptions . Sixteen schizophrenic patients ( treated with atypical antipsycothic drugs ) reporting auditory hallucinations were included in the study . Low frequency rTMS ( 1 Hz ) was performed at the 90 % of resting motor threshold ( MT ) , during 4 sessions in four consecutive days for 15 minutes each application . Eight patients received active stimulation , while eight patients received sham stimulation . Scale for the assessment of positive symptoms ( SAPS ) , scale for the assessment of negative symptoms ( SANS ) and a scale to asses the severity of the auditory hallucinations ( SAH ) were administered at the beginning and at regular intervals during the follow-up . The present study confirms the reduction in auditory hallucinations by means of rTMS . The main finding was the long-term reduction in auditory hallucinations in the active group , with a return to the baseline in the sham group . The negative symptomatology improved only in the later sessions and lasted during the follow-up . The improvements in auditory hallucinations and positive symptomatology increased and lasted during the follow-up till the end-point . These data suggest that this approach may lead to an alternative somatic intervention for auditory hallucination in patients with schizophrenia Repetitive transcranial magnetic stimulation ( rTMS ) has been tried therapeutically in major depression . In order to investigate the therapeutic efficacy of rTMS in psychotic patients , 12 participants ( four women , eight men ) with schizophrenia according to DSM-IV criteria , aged 25 to 63 years ( mean ( ± s.d ) 40.4 ± 11.0 ) , were enrolled in the study . Following a double-blind crossover design , patients were treated at r and om with 2 weeks of daily left prefrontal rTMS ( 20 2 s 20 Hz stimulations at 80 % motor threshold over 20 min , dorsolateral preforntal cortex ) and 2 weeks of sham stimulation . The Brief Psychiatric Rating Scale decreased under active rTMS ( p < 0.05 ) , whereas depressive symptoms ( BDI ) and anxiety ( STAI ) did not change significantly . Prefrontal rTMS might be effective in the non-pharmacological treatment of psychotic patients BACKGROUND Several studies have applied low-frequency repetitive transcranial magnetic stimulation ( rTMS ) directed at the left temporoparietal area ( TP ) for the treatment of auditory verbal hallucinations ( AVH ) , but findings on efficacy are inconsistent . Furthermore , recent functional magnetic resonance imaging ( fMRI ) studies indicate that the left TP is not a general focus of activation during the experience of AVH . The aims of this study are twofold : to investigate the effects of rTMS on AVH in a double blind , r and omized , sham-controlled study ; and to investigate whether the efficacy can be improved when rTMS is guided by individual fMRI scans of hallucinatory activation . METHODS Sixty-two patients with medication-resistant AVH were r and omized over three conditions : rTMS targeted at the area of maximal hallucinatory activation calculated from individual fMRI scans during AVH , rTMS directed at the left TP , and sham treatment . Repetitive TMS was applied during 15 sessions of 20 min each , at 1 Hz and 90 % of the individual motor threshold . The severity of AVH and other psychotic symptoms were monitored during treatment and 3-month follow-up , with the Auditory Hallucination Rating Scale , the Positive and Negative Syndrome Scale , and the Psychotic Symptom Rating Scales . RESULTS The effects of fMRI-guided rTMS and left TP rTMS on the severity of AVH were comparable to those of sham treatment . No differences in severity of general psychotic symptoms were found among the three treatment conditions . CONCLUSIONS Low-frequency rTMS administered to the left TP or to the site of maximal hallucinatory activation is not more effective for medication-resistant AVH than sham treatment OBJECTIVE Some 25%–30 % of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs . Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation ( tDCS ) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms , respectively . The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms . METHOD Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were r and omly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays . The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex . RESULTS Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation , with a mean diminution of 31 % ( SD=14 ; d=1.58 , 95 % CI=0.76–2.40 ) . The beneficial effect on hallucinations lasted for up to 3 months . The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale ( d=0.98 , 95 % CI=0.22–1.73 ) , especially for the negative and positive dimensions . No effect was observed on the dimensions of disorganization or gr and iosity/excitement . CONCLUSIONS Although this study is limited by the small sample size , the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia The effects of transcranial magnetic stimulation ( TMS ) on hallucination severity and neurocognition were studied in 9 medication-resistant hallucinating patients . A statistically significant improvement was observed on a hallucination scale after 10 days of TMS at the left auditory cortex Previous studies suggest that antipsychotic medications may alter cortical inhibition ( CI ) . The current study was design ed to determine if typical or atypical antipsychotics indeed alter CI in healthy subjects using three CI paradigms as measured with transcranial magnetic stimulation ( TMS ) : short interval intracortical inhibition ( SICI ) , cortical silent period ( CSP ) and transcallosal inhibition ( TCI ) . CI was measured before , 6 and 24 h after being r and omly assigned to receive a single dose of 2 mg haloperidol ( n=8 ) , 10 mg olanzapine ( n=10 ) or placebo ( n=9 ) . There was no significant effect on any measure of CI at 6 and 24 h after receiving olanzapine , haloperidol or placebo . Moreover , no significant change in the motor threshold was observed across the three medication groups . Therefore , single administration of an antipsychotic has no effect on CI or resting motor threshold . Whether chronic , repeated administration of antipsychotics has effects on CI requires further investigation |
11,163 | 25,322,302 | We observed differences for costs and health service utilization , although these were often small in magnitude .
Across clinical setting s , new generation CDSSs integrated with EHRs do not affect mortality and might moderately improve morbidity outcomes | null | null |
11,164 | 18,681,783 | Overall , evidence indicates associations of the UGT1A1 ( * ) 28 variant genotype with toxicity after irinotecan treatment , mutations in GSTP1 - 105 with improved treatment outcome and the XPD-751 variant genotype with poor treatment outcome after oxaliplatin treatment , and amplification of the EGFR gene with improved treatment outcome after therapy with monoclonal antibodies . | Pharmacological treatment of colorectal cancer has improved survival rates in recent years .
Individual genetic variation in genes associated with metabolism and targets of commonly used drugs can be responsible for variability in treatment outcome and toxicity .
Diverse study design s have been used and heterogeneous end points evaluated by studies assessing the association of genetic markers with treatment outcome . | 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 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 PURPOSE Stage II and III adenocarcinoma of the rectum has an overall 5-year survival rate of approximately 50 % , and tumor recurrence remains a major problem despite an improvement in local control through chemotherapy and radiation . The efficacy of chemoradiation therapy may be significantly compromised as a result of interindividual variations in clinical response and host toxicity . Therefore , it is imperative to identify those patients who will benefit from chemoradiation therapy and those who will develop recurrent disease . In this study , we tested whether a specific pattern of 21 polymorphisms in 18 genes involved in the critical pathways of cancer progression ( i.e. , drug metabolism , tumor microenvironment , cell cycle regulation , and DNA repair ) will predict the risk of tumor recurrence in rectal cancer patients treated with chemoradiation . PATIENTS AND METHODS A total of 90 patients with Stage II or III rectal cancer treated with chemoradiation were genotyped using polymerase chain reaction (PCR)-based techniques for 21 polymorphisms . RESULTS A polymorphism in interleukin (IL)-8 was individually associated with risk of recurrence . Classification and regression tree analysis of all polymorphisms and clinical variables developed a risk tree including the following variables : node status , IL-8 , intracellular adhesion molecule-1 , transforming growth factor-beta , and fibroblast growth factor receptor 4 . CONCLUSION Genomic profiling may help to identify patients who are at high risk for developing tumor recurrence , and those who are more likely to benefit from chemoradiation therapy . A larger prospect i ve study is needed to vali date these preliminary data using germline polymorphisms on tumor recurrences in rectal cancer patients treated with chemoradiation In this marker evaluation study , we tested whether distinct patterns of functional genomic polymorphisms in genes involved in drug metabolic pathways and DNA repair that predict clinical outcome to 5-fluorouracil (5-FU)/oxaliplatin chemotherapy in patients with advanced colorectal cancer could be identified . Functional polymorphisms in DNA-repair genes XPD , ERCC1 , XRCC1 , XPA , and metabolising genes glutathione S-transferase GSTP1 , GSTT1 , GSTM1 , and thymidylate synthase ( TS ) were assessed retrospectively in 106 patients with refractory stage IV disease who received 5-FU/oxaliplatin combination chemotherapy , using a polymerase chain reaction-based RFLP technique . Favourable genotypes from polymorphisms in XPD-751 , ERCC1 - 118 , GSTP1 - 105 , and TS-3′-untranslated region ( 3′UTR ) that are associated with overall survival were identified . After adjustment for performance status , the relative risks of dying for patients who possessed the unfavourable genotype were : 3.33 for XPD-751 ( P=0.037 ) , 3.25 for GSTP1 - 105 ( P=0.072 ) , 2.05 for ERCC1 - 118 ( P=0.037 ) , and 1.65 for TS-3′UTR ( P=0.091 ) when compared to their respective beneficial genomic variants . Combination analysis with all four polymorphisms revealed that patients possessing ⩾2 favourable genotypes survived a median of 17.4 months ( 95 % confidence interval ( CI ) : 9.4 , 26.5 ) compared to 5.4 months ( 95 % CI : 4.3 , 6.0 ) in patients with no favourable genotype . Patients who carried one favourable genotype demonstrated intermediate survival of 10.2 months ( 95 % CI : 6.8 , 15.3 ; P<0.001 ) . Polymorphisms in the TS-3′UTR and GSTP1 - 105 gene were also associated with time to progression . After adjustment for performance status , patients with an unfavourable TS-3′UTR genotype had a relative risk of disease progression of 1.76 ( P=0.020 ) and those with the unfavourable GSTP1 - 105 genotype showed a relative risk of progression of 2.00 ( P=0.018 ) . The genomic polymorphisms XPD-751 , ERCC1 - 118 , GSTP1 - 105 , and TS-3′UTR may be useful in predicting overall survival and time to progression of colorectal cancer in patients who receive 5-FU/oxaliplatin chemotherapy . These findings require independent prospect i ve confirmation BACKGROUND The antiepidermal growth factor receptor ( antiEGFR ) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10 % of patients with metastatic colorectal cancer that is resistant to chemotherapy . The molecular mechanisms underlying clinical response or resistance to these agents are unknown . METHODS Tumours from 31 patients with metastatic colorectal cancer who had either an objective response ( n=10 ) or stable disease or progressive disease ( n=21 ) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors . Specifically , we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS , BRAF , and PIK3CA . RESULTS Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation ( FISH ) had an increased EGFR copy number . By contrast , one of 21 non-responders assessable by FISH had an increased EGFR copy number ( p<0.0001 for responders vs non-responders , Fisher 's exact test ) . The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA , KRAS , and BRAF did not correlate with disease response . In colorectal-cancer cell lines , the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR . INTERPRETATION We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number Thymidylate synthase [ TS , ( EC 2.1.1.45 ) ] is the target enzyme in 5-fluorouracil treatment . Recently , the DNA polymorphism of this gene has been found to affect TS protein ( pTS ) expression . However , no prospect i ve studies have been performed to evaluate the influence of this polymorphism on the clinical efficacy of 5-FU-based adjuvant chemotherapy for colorectal cancer ( CRC ) . In this study , we investigated the genotype of TS and immunopathological findings of pTS in 161 colon cancer specimens from patients who were registered in a prospect i ve adjuvant immunochemotherapy clinical trial . The clinical course and prognosis of these patients were checked after the study had been completed . This study comprised 11 ( 6.8 % ) cases of 2R/2R , 40 ( 24.8 % ) of 2R/3R , and 110 ( 68.3 % ) of 3R/3R genotypes . All of the 2R/2R cases were still alive at the time of analysis although this finding was not statistically significant . In this prospect i ve examination on a r and omized controlled trial , the patients with colon cancer of the 2R/2R TS genotype may be good responders to 5-FU-based adjuvant chemotherapy . Furthermore , differences in the proportions of the TS genotypes can account for the interracial differences in the adverse effects of 5-FU-based chemotherapy Purpose : We investigated whether the determination of orotate phosphoribosyltransferase ( OPRT ) and thymidylate synthase ( TYMS ) polymorphisms could predict the toxicity of 5-fluorouracil ( 5-FU ) in colorectal cancer patients . Experimental Design : The determination of OPRT and TYMS genotypes were done in genomic DNA extracted from blood by PCR amplification in 69 patients treated with bolus 5-FU as adjuvant chemotherapy . Associations between these polymorphisms and toxicity were evaluated retrospectively . Results : The Ala allele in OPRT Gly213Ala polymorphism and the two t and em repeats ( 2R ) in TYMS promoter polymorphism were associated with grade 3 to 4 neutropenia and diarrhea . The multivariate logistic regression models revealed that only TYMS promoter polymorphism had an independent value to predict grade 3 to 4 neutropenia [ odds ratio , 19.2 for patients with the 2R allele compared with patients with homozygous with the three repeat ( 3R ) alleles ] , whereas both OPRT and TYMS promoter polymorphisms were independent predictive factors for grade 3 to 4 diarrhea ( odds ratio , 13.3 for patients with the Ala allele compared with patients in the Gly/Gly genotype and 11.1 for patients with the 2R allele compared with patients in the 3R/3R genotype ) . A significant difference was observed in the time to onset of severe toxicity , defined as grade 4 neutropenia and /or grade 3 to 4 gastrointestinal toxicities according to OPRT and TYMS promoter polymorphisms . Conclusion : OPRT Gly213Ala polymorphism seems to be a useful marker for predicting toxicity to bolus 5-FU chemotherapy . Prospect i ve translational treatment trials including larger number of patients are needed to confirm our results Purpose : Irinotecan ( CPT-11 ) is approved in metastatic colorectal cancer treatment and can cause severe toxicity . The main purpose of our study was to assess the role of different polymorphisms on the occurrence of hematologic toxicities and disease-free survival in high-risk stage III colon cancer patients receiving 5-fluorouracil ( 5FU ) and CPT-11 adjuvant chemotherapy regimen in a prospect i ve r and omized trial . Experimental Design : Four hundred patients were r and omized in a phase III trial comparing LV5FU2 to LV5FU2 + CPT-11 . DNA from 184 patients was extracted and genotyped to detect nucleotide polymorphism : 3435C > T for ABCB1 , 6986A > G for CYP3A5 , UGT1A1 * 28 and −3156G > A for UGT1A1 . Results : Genotype frequencies were similar in both treatment arms . In the test arm , no significant difference was observed in toxicity or disease-free survival for ABCB1 and CYP3A5 polymorphisms . UGT1A1 * 28 homozygous patients showed more frequent severe hematologic toxicity ( 50 % ) than UGT1A1 * 1 homozygous patients ( 16.2 % ) , P = 0.06 . Moreover , patients homozygous for the mutant allele of −3156G > A UGT1A1 polymorphism showed more frequent severe hematologic toxicity ( 50 % ) than patients homozygous for wild-type allele ( 12.5 % ) , P = 0.01 . This toxicity occurred significantly earlier in homozygous mutant than wild-type homozygous patients ( P = 0.043 ) . In a Cox model , the hazard ratio for severe hematologic toxicity is significantly higher for patients with the A/A compared with the G/G genotype [ hazard ratio , 8.4 ; 95 % confidence interval , 1.9–37.2 ; P = 0.005 ] . Conclusions : This study supports the clinical utility of identification of UGT1A1 promoter polymorphisms before LV5FU2 + CPT-11 treatment to predict early hematologic toxicity . The −3156G > A polymorphism seems to be a better predictor than the UGT1A1 (TA)6TAA>(TA)7TAA polymorphism Seventy-nine patients with advanced , measurable , metastatic colorectal cancer previously unexposed to chemotherapy were r and omly assigned to treatment with either fluorouracil ( FUra ) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium ( 500 mg/m2/d ) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy . Patients whose disease progressed on treatment with FUra alone were , if eligible , crossed over to receive leucovorin and FUra . Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements . The treatment arms were well balanced for prognostic criteria including performance status , age , prior radiotherapy , distribution of metastatic sites , and on- study carcinoembryonic antigen ( CEA ) , lactic dehydrogenase , and serum albumin . FUra plus leucovorin was superior to FUra alone for response ( P = .0019 ) and for time to progression or death ( log-rank , P = .045 ) . Response rates were 16 of 36 ( 44 % ) versus five of 40 ( 13 % ) , and median time to progression or death was 164 versus 120 days in the two arms of the trial , respectively . Overall survival , however , while longer in the FUra and leucovorin arm was not significantly so . An analysis of the toxicities experienced by the patients in the two treatment groups showed that , except for significantly more stomatitis in the leucovorin arm of the study , the side effects experienced by patients treated with either regimen were comparable . These results suggest that the efficacy of FUra in patients with advanced , measurable , metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium Objective The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase ( MTHFR ) C677 T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter , namely the variable number t and em repeat polymorphism ( TS VNTR ) and the intrarepeat G to C single nucleotide polymorphism ( TS SNP ) , are predictive markers of tumor regression in rectal cancer patients following preoperative chemoradiotherapy . Basic methods Blood sample s from 125 patients with primary adenocarcinoma of the mid – low rectum who received 5-fluorouracil-based chemotherapy and external beam radiotherapy ( median dose 48.4 Gy ) , 125 patients ( women n=45 , men n=80 ; median age 60 years , range 31–79 years ) were genotyped . Response to preoperative treatment was evaluated employing the Tumor Regression Grade criteria . On the basis of the pathologic response , patients were classified as responders ( TRG 1–2 , n=48 ) and non-responders ( TRG 3–5 , n=74 ) . Three patients were excluded because of insufficient data . Main results Among the polymorphic variants examined , the MTHFR 677T-1298A haplotype was , upon univariate analysis , the only variable found associated with tumor regression ( P=0.004 ) . Moreover , at multivariate analysis , the MTHFR 677T-1298A haplotype was an independent predictor of tumor regression . Patients not carrying the MTHFR 677T-1298A haplotype ( odds ratio 0.29 , 95 % confidence interval 0.13–0.64 , P=0.002 ) displayed a higher response rate than patients with the MTHFR 677T-1298A haplotype . Conclusions Unlike TS VNTR and SNP polymorphisms , MTHFR 677T-1298A haplotype in genomic DNA has the potential to be a predictive marker of tumor response in rectal cancer patients su bmi tted to preoperative Fluorouracil ( 5-FU ) is widely used in the treatment of colorectal cancer . Methylenetetrahydrofolate reductase ( MTHFR ) may play a central role in the action of 5-FU , an inhibitor of thymidylate synthase , by converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate . The aim of this study was to ascertain whether two polymorphisms in the MTHFR gene ( 677C > T and 1298 A > C ) could be used as genomic predictors of clinical response to fluoropyrimidine-based chemotherapy ( in combination with irinotecan or oxaliplatin ) . Ninety-four patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-containing chemotherapy as a first line treatment were studied . The results suggest that the MTHFR genotype can not be considered as an independent factor of outcome in colorectal cancer patients under 5-FU-based chemotherapy PURPOSE To test the hypotheses of whether the relative mRNA expression of the thymidylate synthase ( TS ) gene and the excision cross-complementing ( ERCC1 ) gene are associated with response to and survival of fluorouracil (5-FU)/oxaliplatin chemotherapy in metastatic colorectal cancer . PATIENTS AND METHODS Patients had progressive stage IV disease after unsuccessful 5-FU and irinotecan chemotherapy . All patients were evaluated for eligibility for a compassionate 5-FU/oxaliplatin protocol . cDNA was derived from paraffin-embedded tumor specimens to determine TS and ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based , real-time reverse transcriptase polymerase chain reaction . RESULTS The median TS gene expression level from 50 metastasized tumors was 3.4 x 10(-3 ) ( minimum expression , 0.18 x 10(-3);maximum expression , 11.5 x 10(-3 ) ) , and the median ERCC1 gene expression level was 2.53 x 10(-3 ) ( minimum , 0.0 ; maximum , 14.61 x 10(-3 ) ) . The gene expression cutoff values for chemotherapy nonresponse were 7.5 x 10(-3 ) for TS and 4.9 x 10(-3 ) for ERCC1 . The median survival time for patients with TS < or= 7.5 x 10(-3 ) ( 43 of 50 patients ) was 10.2 months , compared with 1.5 months for patients with TS greater than 7.5 x 10(-3 ) ( P < .001 ) . Patients with ERCC1 expression < or= 4.9 x 10(-3 ) ( 40 of 50 patients ) had a median survival time of 10.2 months , compared with 1.9 months for patients with ERCC1 expression greater than 4.9 x 10(-3 ) ( P < .001 ) . A TS of 7.5 x 10(-3 ) segregated significantly into response , stable disease , and progression ( P = .02 ) , whereas the association between ERCC1 and response did not reach statistical significance ( P = .29 ) . CONCLUSION These data suggest that intratumoral ERCC1 mRNA and TS mRNA expression levels are independent predictive markers of survival for 5-FU and oxaliplatin combination chemotherapy in 5-FU-resistant metastatic colorectal cancer . Precise definition of the best TS cut point will require further analysis in a large , prospect i ve study PURPOSE We studied the prognostic value of thymidylate synthase ( TS ) expression in primary colorectal cancer ( CRC ) and the role of TS expression as a predictor of chemotherapeutic benefit in patients treated with adjuvant chemotherapy . PATIENTS AND METHODS TS expression was immunohistochemically assessed on tumor sections from 862 patients with CRC Dukes ' stages B and C enrolled onto r and omized trials evaluating fluorouracil (5-FU)-based adjuvant chemotherapy . RESULTS TS expression was an independent prognostic factor for disease-free ( P = .05 ) and overall survival ( P = .05 ) . In the subgroup treated with surgery alone , TS was an independent prognostic factor for disease-free ( P < .001 ) and overall survival ( P = .001 ) , whereas this was not the case in the subgroup of adjuvantly treated patients . Patients whose tumors expressed high TS levels had a tendency to improved outcome after adjuvant therapy ( not significant ) . The group whose tumors expressed the highest TS grade , grade 3 ( 34 % of the patients ) , had a significantly longer disease-free survival if they were treated with adjuvant therapy compared with surgery alone ( multivariate analyses , P = .02 ) , whereas patients whose tumors expressed low TS levels ( 28 % of the patients ) had an impaired outcome after adjuvant therapy ( multivariate analyses : disease-free survival , P = .01 ; overall survival , P = .01 ) . CONCLUSION TS expression predicts for survival independent of Dukes ' stage in patients with CRC treated with surgery alone . The study indicates that patients with high TS levels may benefit from adjuvant 5-FU-based chemotherapy . However , patients with low TS levels seem to have a worse outcome when treated with adjuvant chemotherapy The present study aim ed to prospect ively investigate the influence of thymidylate synthase ( TS ) polymorphisms ( 5′-TSER , 3′-TSUTR ) on the disease-free survival ( DFS ) and overall survival ( OS ) of patients with colorectal cancer ( CRC ) who were treated with adjuvant 5-fluorouracil ( 5-FU ) therapy . Patients were followed up for 19±14 months ( median±SD ) . TS genotypes were determined from the peripheral blood mononuclear cells of 166 patients by polymerase chain reaction – polyacrylamide gel electrophoresis and restriction fragment length polymorphism methods . 5′-TSER 3R homozygotes showed significantly longer DFS ( P=0.048 ) and OS ( P=0.009 ) . The 5′-TSER and 3′-TSUTR genotype combination groups showed a significant difference for DFS ( P=0.039 ) and OS ( P=0.029 ) . Significantly better DFS ( P=0.049 ) and OS ( P=0.043 ) were observed for 6 bp/6 bp genotypes in 5′-TSER heterozygotes ( n=80 ) . Based on this , and on hazard ratios obtained by Cox regression analysis of the DFS of genotype – combinations , the patients were classified as belonging to prognostic groups A and B. The DFS and OS of these two groups showed a highly significant difference ( P=0.002 and 0.001 ) . In the multivariate Cox regression model , beside tumour location , the prognostic classification ( groups A and B ) proved to be an independent prognostic factor . Our data suggest that those TS genotypes and their combinations ( group A : 3R/3R with any 3′-TSUTR genotype and 2R/3R with 6 bp/6 bp ) , which have been reported earlier as having high TS expression , predict significantly longer DFS and OS . We found that a combination of germline TS polymorphisms is an independent prognostic marker in selecting CRC patients with worse prognosis , and it may be worthwhile to examine whether these patients would benefit from an alternative therapy The study aim ed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer ( CRC ) patients treated with single-agent Cetuximab . Polymorphisms of interest in the EGFR pathway include : cyclin D1 ( CCND1 ) A870 G , cyclooxygenase 2 ( Cox-2 ) G-765C , epidermal growth factor ( EGF ) A61 G , epidermal growth factor receptor ( EGFR ) codon R497 K , EGFR CA dinucleotide repeat in intron 1 , interleukin (IL)-8 T-251A and vascular endothelial growth factor ( VEGF ) C936 T gene polymorphisms . Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab . Using the polymerase chain reaction-restriction fragment length polymorphism method , gene polymorphisms of CCND1 , COX-2 , EGF , EGFR , IL-8 and VEGF were assessed from genomic DNA extracted from blood sample s. A significant association was found between the CCND1 A870 G polymorphism and overall survival in our 39 CRC subjects . Patients with the AA homozygous genotype survived for a median of 2.3 months [ 95 % confidence interval (CI)=2.1–5.7 ] , whereas those with any G allele ( AG , GG genotype ) survived for a median of 8.7 months ( 95 % CI=4.4–13.5 ) ( P=0.019 , log-rank test ) . When we analysed the cyclin D1 and EGF polymorphisms together , patients with favourable genotypes ( EGF any A allele and CCND1 any G allele ) showed a median survival time of 12 months ( 95 % CI=4.8–15.2 ) , whereas patients with any two unfavourable genotypes ( EGF GG or CCND1 AA ) showed a median survived time of 4.4 months ( 95 % CI=2.1–5.7 ) ( P=0.004 , log-rank test ) . The findings of this pilot study suggest that the cyclin D1 A870 G and the EGF A61 G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab Thymidylate synthase ( TS ) is an important target for chemotherapy drugs such as 5-fluorouracil and raltitrexed . Over-expression of TS has been linked to chemotherapy resistance . A polymorphic t and em repeat sequence in the 5 ' untranslated region ( 5'UTR ) of the human TS gene ( TSER ) has been shown to influence TS expression . The presence of a triple t and em repeat ( TSER*3 ) increases in vitro TS expression compared to a double t and em repeat ( TSER*2 ) and is associated with higher in vivo tumor TS activity . The polymorphism of this promoter enhancer region has not been extensively studied in patients with cancer and may represent a possible mechanism of intrinsic resistance to TS inhibitors . In this study , PCR analysis of genomic DNA from 121 patients with colorectal cancer demonstrated 29 % of patients were homozygous for TSER*3 , 16 % were homozygous for TSER*2 and 55 % were heterozygous . In 44/45 microdissected tumors the TS enhancer genotype was identical between paired sample s of colorectal tumor and normal tissue . In 24 patients receiving a bolus/infusion 5-fluorouracil ( 5FU ) regimen for metastatic colorectal cancer , 22 % of non-responders to chemotherapy were homozygous for TSER*2 compared with 40 % of responders . Median survival dropped from 16 months for homozygous TSER*2 to 12 months for homozygous TSER*3 . This is consistent with previous studies where higher TS expression was associated with poor response to TS inhibitors . Prospect i ve analysis of the influence of the TS polymorphism on patient outcome is warranted PURPOSE To analyze thymidylate synthase ( TS ) and methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphism with respect to fluorouracil ( FU ) sensitivity . PATIENTS AND METHODS The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospect i ve trial with 51 patients also with measurable metastases . All patients were treated with FU and leucovorin . The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes . RESULTS The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups . The difference of response rate translated to a difference in time to progression . Similar results were observed in the retrospective analysis and the prospect i ve confirmatory trial . CONCLUSION The analysis of gene polymorphism allows delineation of a group of patients ( 30 % ) with a response rate to a single drug of approximately 50 % . This information should be used in the design of tailored treatment In the current Phase II study , the authors evaluated the association between genomic polymorphic variants in uridine diphosphate glucuronosyl transferase ( UGT1A1 ) , methylenetetrahydrofolate reductase ( MTHFR ) , and thymidylate synthase ( TS ) genes , and the incidence of the adverse effects of irinotecan and raltitrexed in previously heavily treated patients with metastatic colorectal carcinoma The causes of interpatient variation in severe toxicity result ing from treatment with weekly 5-fluorouracil (5-FU)/ leucovorin ( LV ) are poorly understood . This study was undertaken to examine the contribution of commonly occurring polymorphisms in the dihydropyrimidine dehydrogenase ( DPYD ) gene to interpatient variability in 5-FU pharmacokinetics and toxicity . Patients with stage III/IV colorectal cancer were treated by bolus intravenous ( I.V. ) injection with 500 mg/m2 doses of 5-FU and LV once every week . The pharmacokinetics of 5-FU was determined on weeks 1 and 4 . Genotyping assays were developed for 8 polymorphisms in the DPYD gene . A well-characterized functional polymorphism in the 5 ' untranslated region of the thymidylate synthase ( TS ) gene was also analyzed . A cohort of 22 patients ( 15 male , 7 female ) with a median age of 61 years was evaluated . Although there was no relationship between the area under the plasma concentration time curve ( AUC ) for the first dose of 5-FU and worst- grade toxicity during the first cycle of therapy , 3 of the 4 patients in whom the AUC on week 4 was more than equal to 5 microgram/h/mL greater than the value for the first dose experienced grade 3/4 toxicity during subsequent treatment . Among the 8 polymorphisms in the DPYD gene , 7 were found to vary in the study population but none were significantly associated with the AUC of 5-FU . There was no relationship between the DPYD and TS genotypes examined and 5-FU toxicity . Extensive polymorphism in the DPYD gene was observed ; however , no conclusive correlations existed between the DPYD and TS genotype and 5-FU pharmacokinetics or toxicity . Decreases in 5-FU clearance in certain patients may provide insight into the increased toxicity following repetitive cycles of treatment with weekly I.V. bolus 5-FU . The present study offers useful themes for undertaking larger prospect i ve pharmacogenetic studies in the future 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 |
11,165 | 23,756,457 | Based on the best current available evidence ( grade A ) , we recommend dry needling , compared to sham or placebo , for decreasing pain immediately after treatment and at 4 weeks in patients with upper-quarter MPS . | BACKGROUND Myofascial pain syndrome ( MPS ) is associated with hyperalgesic zones in muscle called myofascial trigger points .
When palpated , active myofascial trigger points cause local or referred symptoms , including pain .
Dry needling involves inserting an acupuncture-like needle into a myofascial trigger point , with the goal of reducing pain and restoring range of motion .
OBJECTIVE To explore the evidence regarding the effectiveness of dry needling to reduce pain in patients with MPS of the upper quarter . | OBJECTIVES To compare the efficacies of dry needling of trigger points ( TrPs ) with and without paraspinal needling in myofascial pain syndrome of elderly patients . DESIGN Single-blinded , r and omized controlled trial . SUBJECTS Forty ( 40 ) subjects , between the ages of 63 and 90 with myofascial pain syndrome of the upper trapezius muscle . INTERVENTIONS Eighteen ( 18 ) subjects were treated with dry needling of all the TrPs only and another 22 with additional paraspinal needling on days 0 , 7 , and 14 . RESULTS At 4-week follow-up the results were as follows : ( 1 ) TrP and paraspinal dry needling result ed in more continuous subjective pain reduction than TrP dry needling only ; ( 2 ) TrP and paraspinal dry needling result ed in significant improvements on the geriatric depression scale but TrP dry needling only did not ; ( 3 ) TrP and paraspinal dry needling result ed in improvements of all the cervical range of motions but TrP dry needling only did not in extensional cervical range of motion ; and ( 4 ) no cases of gross hemorrhage were noted . CONCLUSIONS TrP and paraspinal dry needling is suggested to be a better method than TrP dry needling only for treating myofascial pain syndrome in elderly patients OBJECTIVE We aim ed to evaluate the effectiveness of laser therapy in myofascial pain syndrome treatment . BACKGROUND DATA Myofascial pain syndrome is a disease that is characterized by hypersensitive points called trigger points found in one or more muscles and /or connective tissues . It can cause pain , muscle spasm , sensitivity , stiffness , weakness , limitation of range of motion and rarely autonomic dysfunction . Physical therapy modalities and exercise are used in the treatment of this frequently encountered disease . METHODS The placebo controlled , prospect i ve , long-term follow up study was planned with 60 patients who had trigger points in their upper trapezius muscles . The patients were divided into three groups r and omly . Stretching exercises were taught to each group and they were asked to exercise at home . Treatment duration was 4 weeks . Placebo laser was applied to group 1 , dry needling to group 2 and laser to group 3 . He-Ne laser was applied to three trigger points in the upper trapezius muscles on both sides with 632.8 nm . The patients were assessed at before , post-treatment , and 6 months after-treatment for pain , cervical range of motion and functional status . RESULTS We observed a significant decrease in pain at rest , at activity , and increase in pain threshold in the laser group compared to other groups . Improvement according to Nottingham Health Profile gave the superiority of the laser treatment . However , those differences among the groups were not observed at 6-month follow up . CONCLUSIONS Laser therapy could be useful as a treatment modality in myofascial pain syndrome because of its noninvasiveness , ease , and short-term application OBJECTIVE EMG examination at tender points affects myofascial pain symptoms related to cervical nerve root irritation . METHODS Consecutive patients with neck and arm pain had physical examinations immediately before and after having EMGs of bilateral C3-C8 myotomes . Patients were r and omly chosen for EMG either at the most tender point along the palpated myofascial b and or at a nonselected site . The myotomal presence of > or = 30 % incidence of normal duration and amplitude , and polyphasic motor unit potentials confirm the diagnosis of cervical nerve root irritation . RESULTS 52 % returned patient question naires 2 weeks post EMG examination . Group I ( 82/122 patients [ 67.2 % ] ) , averaged pain relief of 51.8 + /- 21.9 % , a mean of 10.2 + /- 8 days ; 14 % had > or = 75 % relief . The number of days of pain relief correlated positively with the percentage of pain relief ( p < 0.005 ) , but negatively with the number of nerve roots involved on EMG ( p < 0.05 ) . Group 2 ( 23/42 patients [ 54.8 % ] ) , averaged relief of 39.0 + /- 18.7 % , lasting 8.8 + /- 11.2 days . None had > or = 75 % pain relief . Both groups ' duration of pain symptoms affected onset of relief . Evidence of bilateral multiple-level cervical nerve root irritation , especially noted at bilateral C6 and C7 levels . CONCLUSION EMG at tender points on myofascial b and s tends to improve symptoms . Needling these points elicits motor endplate activity and twitches , and induces more relief than when needling r and om points & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Background Rotator cuff tendinopathy and subacromial impingement syndrome present complex patomechanical situations , frequent difficulties in clinical diagnosis and lack of effectiveness in treatment . Based on clinical experience , we have therefore considered the existence of another pathological entity as the possible origin of pain and dysfunction . The hypothesis of this study is to relate subacromial impingement syndrome ( SIS ) with myofascial pain syndrome ( MPS ) , since myofascial trigger points ( MTrPs ) cause pain , functional limitation , lack of coordination and alterations in quality of movement , even prior to a tendinopathy . MTrPs can coexist with any degenerative subacromial condition . If they are not taken into consideration , they could perpetuate and aggravate the problem , hindering diagnosis and making the applied treatments ineffective . The aims and methods of this study are related with providing evidence of the relationship that may exist between this condition and MPS in the diagnosis and treatment of rotator cuff tendonitis and /or SIS . Method / design A descriptive transversal study will be made to find the correlation between the diagnosis of SIS and rotator cuff tendonitis , positive provocation test responses , the existence of active MTrPs and the results obtained with ultrasonography ( US ) and Magnetic Renonance Imaging ( MRI ) . A r and omized double blinded clinical trial will be carried out in experimental conditions : A Protocol ized treatment based on active and passive joint repositioning , stabilization exercises , stretching of the periarticular shoulder muscles and postural reeducation . B. The previously described protocol ized treatment , with the addition of dry needling applied to active MTrPs with the purpose of isolating the efficacy of dry needling in treatment . Discussion This study aims to provide a new vision of shoulder pain , from the perspective of MPS . This syndrome can , by itself , account for shoulder pain and dysfunction , although it can coexist with real conditions involving the tendons . Trail Registration IS RCT N Number : In this study ; we aim ed to compare the efficacy of local anesthetic injection and dry needling methods on pain , cervical range of motion ( ROM ) , and depression in myofascial pain syndrome patients ( MPS ) . This study was design ed as a prospect i ve r and omized controlled study . Eighty patients ( female 52/male 28 ) admitted to a physical medicine and rehabilitation outpatient clinic diagnosed as MPS were included in the study . Patients were r and omly assigned into two groups . Group 1 ( n = 40 ) received local anesthetic injection ( 2 ml lidocaine of 1 % ) and group 2 ( n = 40 ) received dry injecting on trigger points . Both patient groups were given stretching exercises aim ed at the trapezius muscle to be applied at home . Patients were evaluated according to pain , cervical ROM , and depression . Pain was assessed using Visual Analog Scale ( VAS ) and active cervical ROM was measured using goniometry . Beck Depression Inventory ( BDI ) was used to assess the level of depression . There were no statistically significant differences in the pre-treatment evaluation parameters of the patients . There were statistically significant improvements in VAS , cervical ROM , and BDI scores after 4 and 12 weeks in both groups compared to pre-treatment results ( p < 0.05 ) . No significant differences were observed between the groups ( p > 0.05 ) . Our study indicated that exercise associated with local anesthetic and dry needling injections were effective in decrease of pain level in MPS as well as increase of cervical ROM and decrease of depressive mood levels of individuals & NA ; To evaluate immediate effects of two different modes of acupuncture on motion‐related pain and cervical spine mobility in chronic neck pain patients compared to a sham procedure . Thirty‐six patients with chronic neck pain and limited cervical spine mobility participated in a prospect i ve , r and omized , double‐blind , sham‐controlled crossover trial . Every patient was treated once with needle acupuncture at distant points , dry needling ( DN ) of local myofascial trigger points and sham laser acupuncture ( Sham ) . Outcome measures were motion‐related pain intensity ( visual analogue scale , 0–100 mm ) and range of motion ( ROM ) . In addition , patients scored changes of general complaints using an 11‐point verbal rating scale . Patients were assessed immediately before and after each treatment by an independent ( blinded ) investigator . Multivariate analysis was used to assess the effects of true acupuncture and needle site independently . For motion‐related pain , use of acupuncture at non‐local points reduced pain scores by about a third ( 11.2 mm ; 95 % CI 5.7 , 16.7 ; P=0.00006 ) compared to DN and sham . DN led to an estimated reduction in pain of 1.0 mm ( 95 % CI −4.5 , 6.5 ; P=0.7 ) . Use of DN slightly improved ROM by 1.7 ° ( 95 % CI 0.2 , 3.2 ; P=0.032 ) with use of non‐local points improving ROM by an additional 1.9 ° ( 95 % CI 0.3 , 3.4 ; P=0.016 ) . For patient assessment of change , non‐local acupuncture was significantly superior both to Sham ( 1.7 points ; 95 % CI 1.0 , 2.5 ; P=0.0001 ) and DN ( 1.5 points ; 95 % CI 0.4 , 2.6 ; P=0.008 ) but there was no difference between DN and Sham ( 0.1 point ; 95 % CI −1.0 , 1.2 ; P=0.8 ) . Acupuncture is superior to Sham in improving motion‐related pain and ROM following a single session of treatment in chronic neck pain patients . Acupuncture at distant points improves ROM more than DN ; DN was ineffective for motion‐related pain The objective of this study was to test the hypothesis that dry needling is more effective than sham dry needling in the treatment of myofascial pain syndrome ( MPS ) . This was a prospect i ve , double-blinded , r and omized-controlled study conducted in an outpatient clinic . Thirty-nine subjects with established myofascial trigger points were r and omized into two groups : study group ( N = 22 ) and placebo group ( N = 17 ) . Dry needling was applied using acupuncture needles , and sham dry needling was applied in the placebo group . The treatment was composed of six sessions which were performed in 4 weeks ; the first four sessions were performed twice a week ( for 2 weeks ) and the last two , once a week ( for 2 weeks ) . The visual analog scale ( VAS ) and Short Form-36 ( SF-36 ) were used . When compared with the initial values , VAS scores of the dry needling group following the first and sixth sessions were significantly lower ( p = 0.000 and p < 0.000 , respectively ) . When VAS scores were compared between the groups , the first assessment scores were found to be similar , but the second and third assessment scores were found to be significantly lower in the dry needling group ( p = 0.034 and p < 0.001 , respectively ) . When SF-36 scores of the groups were compared , both the physical and mental component scores were found to be significantly increased in the dry needling group , whereas only those of vitality scores were found to be increased significantly in the placebo ( sham needling ) group . The present study shows that the dry needling treatment is effective in relieving the pain and in improving the quality of life of patients with MPS Background : Myofascial pain syndrome ( MPS ) is one of the most common causes of chronic musculoskeletal pain . Several methods have been recommended for the inactivation of trigger points ( TrP ) . Objectives : This prospect i ve , single-blind study was proposed to compare TrP injection with botulinum toxin type A ( BTX-A ) to dry needling and lidocaine injection in MPS . Methods : Eighty-seven trigger points ( cervical and /or periscapular regions ) in 23 female and six male patients with MPS were treated and r and omly assigned to three groups : lidocaine injection ( n=10 , 32 TrP ) , dry needling ( n=10 , 33 TrP ) , and BTX-A injection ( n=9 , 22 TrP ) . Outcome measures : Clinical assessment including cervical range of motion , TrP pain pressure threshold ( PPT ) , pain scores ( PS ) , and visual analog scales for pain , fatigue , and work disability were evaluated at entry and the end of the 4th week . Additionally , depression and anxiety were evaluated with the Hamilton depression and anxiety rating scales , and quality of life was assessed using the Nottingham health profile ( NHP ) . The subjects were also asked to describe side effects . Injection procedure : One milliliter of 0.5 % lidocaine was administered to each TrP in the lidocaine injection group , 10–20 IU of BTX-A to each TrP in the BTX-A group , and dry needling to each TrP in the last group , followed by stretching of the muscle groups involved . The patients were instructed to continue their home exercise programs . Results : Pain pressure thresholds and PS significantly improved in all three groups . In the lidocaine group , PPT values were significantly higher than in the dry needle group , and PS were significantly lower than in both the BTX-A and dry needle groups . In all , visual analog scores significantly decreased in the lidocaine injection and BTX-A groups and did not significantly change in the dry needle group . Disturbance during the injection procedure was lowest in the lidocaine injection group . Quality of life scores assessed by NHP significantly improved in the lidocaine and BTX-A groups but not in the dry needle group . Depression and anxiety scores significantly improved only in the BTX-A-injected group . Conclusions : Injection is more practical and rapid , since it causes less disturbance than dry needling and is more cost effective than BTX-A injection , and seems the treatment of choice in MPS . On the other h and , BTX-A could be selectively used in MPS patients resistant to conventional treatments STUDY DESIGN Prospect i ve observation study . OBJECTIVES To compare the test-retest reliability and longitudinal validity ( sensitivity to change ) of 2 single-item numeric pain rating scales ( NPRSs ) with a 4-item pain intensity measure ( P4 ) . BACKGROUND Pain is a frequent outcome measure for patients seen in physical therapy ; however , the error associated with efficient pain measures , such as the single-item NPRS , is greater than for self-report measures of functional status . Initial evaluation of the P4 suggests that it is more reliable and sensitive to change than the NPRS . METHODS AND MEASURES Two single-item NPRSs and the P4 were administered on 3 occasions -- initial visit ( n = 220 ) , within 72 hours of baseline ( n = 213 ) , and 12 days following baseline assessment ( n = 183)--to patients with musculoskeletal problems receiving physical therapy . Reliability was assessed using a type 2,1 intraclass correlation coefficient . Longitudinal validity was assessed by correlating the measures ' change scores with a retrospective rating of change that included patients ' and clinicians ' perspectives . RESULTS The test-retest reliability and longitudinal validity of the P4 were significantly greater ( P1<.05 ) than both single-item NPRSs . Minimal detectable change of the P4 at the 90 % confidence level was estimated to be a change of 22 % of the scale range ( 9 points ) compared to 27.3 % ( 3 points ) and 31.8 % ( 3.5 points ) for the 2-day NPRS and 24-hour NPRS , respectively . CONCLUSIONS The findings of this study suggest the P4 is more adept at assessing change in pain intensity than popular versions of single-item NPRSs Tsai C-T , Hsieh L-F , Kuan T-S , Kao MJ , Chou L-W , Hong C-Z : Remote effects of dry needling on the irritability of the myofascial trigger point in the upper trapezius muscle . Objective : To investigate the remote effect of dry needling on the irritability of a myofascial trigger point in the upper trapezius muscle . Design : Thirty-five patients with active myofascial trigger points in upper trapezius muscles were r and omly divided into two groups : 18 patients in the control group received sham needling , and 17 patients in the dry-needling group received dry needling into the myofascial trigger point in the extensor carpi radialis longus muscle . The subjective pain intensity , pressure pain threshold , and range of motion of the neck were assessed before and immediately after the treatment . Results : Immediately after dry needling in the experimental group , the mean pain intensity was significantly reduced , but the mean pressure threshold and the mean range of motion of cervical spine were significantly increased . There were significantly larger changes in all three parameters of measurement in the dry-needling group than that in the control group . Conclusions : This study demonstrated the remote effectiveness of dry needling . Dry needling of a distal myofascial trigger point can provide a remote effect to reduce the irritability of a proximal myofascial trigger point 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 . This study was design ed to investigate the effects of injection with a local anesthetic agent or dry needling into a myofascial trigger point ( TrP ) of the upper trapezius muscle in 58 patients . Trigger point injections with 0.5 % lidocaine were given to 26 patients ( Group I ) , and dry needling was performed on TrPs in 15 patients ( Group II ) . Local twitch responses ( LTRs ) were elicited during multiple needle insertions in both Groups I and II . In another 17 patients , no LTR was elicited during TrP injection with lidocaine ( 9 patients , group Ia ) or dry needling ( 8 patients , group IIa ) . Improvement was assessed by measuring the subjective pain intensity , the pain threshold of the TrP and the range of motion of the cervical spine . Significant improvement occurred immediately after injection into the patients in both group I and group II . In Groups la and Ib , there was little change in pain , tenderness or tightness after injection . Within 2 - 8 h after injection or dry needling , soreness ( different from patients ' original myofascial pain ) developed in 42 % of the patients in group I and in 100 % of the patients in group II . Patients treated with dry needling had postinjection soreness of significantly greater intensity and longer duration than those treated with lidocaine injection . The author concludes that it is essential to elicit LTRs during injection to obtain an immediately desirable effect . TrP injection with 0.5 % lidocaine is recommended , because it reduces the intensity and duration of postinjection soreness compared with that produced by dry Abstract Trigger point injections with different solutions have been studied mainly with regard to the management of myofascial pain ( MFP ) patient management . However , few studies have analyzed their effect in a chronic headache population with associated MFP . The purpose of this study was to assess if trigger point injections using lidocaine associated with corticoid would be better than lidocaine alone , as in comparison with dry-needling in for the management of local pain and associated headache management . Forty-five ( 45 ) myofascial pain patients with headaches that could be reproduced by activating at least one trigger point , were r and omly assigned into one of the three groups : G1 , dry-needling , G2 , 0.25 % lidocaine , at 0.25 % and G3 , 0.25 % lidocaine at 0.25 % associated with corticoid , and were assessed during a 12 week period . Levels of pain intensity , frequency and duration , local post-injection sensitivity , obtainment time and duration of relief , and the use of rescue medication were evaluated . Statistically , all three groups showed favorable results for the evaluated requisites ( p≤0.05 ) , but only for post-injection sensitivity did the association of lidocaine with corticoid present the best results and ingestion of rescue medication INTRODUCTION There is some evidence for the efficacy of acupuncture in chronic neck pain ( CNP ) treatment , but it remains unclear which acupuncture modes are most effective . Objective was to evaluate the effects of trigger point acupuncture on pain and quality of life ( QOL ) in CNP patients compared to three other acupuncture treatments ( acupoints , non-trigger point and sham treatment ) . METHODS Forty out- patients ( 29 women , 11 men ; age range : 47 - 80 years ) from the Department of Orthopaedic Surgery , Meiji University of Oriental Medicine , with non-radiating CNP for at least 6 months and normal neurological examination were r and omised to one of four groups over 13 weeks . Each group received two phases of acupuncture treatment with an interval between them . The acupoint group ( st and ard acupuncture ; SA , n=10 ) received treatment at traditional acupoints for neck pain , the trigger point ( TrP , n=10 ) and non-trigger point ( non-TrP , n=10 ) groups received treatment at tenderness points for the same muscle , while the other acupuncture group received sham treatments on the trigger point ( SH , n=10 ) . Outcome measures were pain intensity ( visual analogue scale ; VAS 0 - 100 mm ) and disease specific question naire ( neck disability index ; NDI , 60-point scale ) . RESULTS After treatment , the TrP group reported less pain intensity and improved QOL compared to the SA or non-TrP group . There was significant reduction in pain intensity between the treatment and the interval for the TrP group ( p<0.01 , Dunnett 's multiple test ) , but not for the SA or non-TrP group . CONCLUSION These results suggest that trigger point acupuncture therapy may be more effective on chronic neck pain in aged patients than the st and ard acupuncture therapy Hsieh Y-L , Kao M-J , Kuan T-S , Chen S-M , Chen J-T , Hong C-Z : Dry needling to a key myofascial trigger point may reduce the irritability of satellite myofascial trigger points . Am J Phys Med Rehabil 2007;86:397–403 . Objective : To investigate the changes in pressure pain threshold of the secondary ( satellite ) myofascial trigger points ( MTrPs ) after dry needling of a primary ( key ) active MTrP. Design : Single blinded within-subject design , with the same subjects serving as their own controls ( r and omized ) . Fourteen patients with bilateral shoulder pain and active MTrPs in bilateral infraspinatus muscles were involved . An MTrP in the infraspinatus muscle on a r and omly selected side was dry needled , and the MTrP on the contralateral side was not ( control ) . Shoulder pain intensity , range of motion ( ROM ) of shoulder internal rotation , and pressure pain threshold of the MTrPs in the infraspinatus , anterior deltoid , and extensor carpi radialis longus muscles were measured in both sides before and immediately after dry needling . Results : Both active and passive ROM of shoulder internal rotation , and the pressure pain threshold of MTrPs on the treated side , were significantly increased ( P < 0.01 ) , and the pain intensity of the treated shoulder was significantly reduced ( P < 0.001 ) after dry needling . However , there were no significant changes in all parameters in the control ( untreated ) side . Percent changes in the data after needling were also analyzed . For every parameter , the percent change was significantly higher in the treated side than in the control side . Conclusions : This study provides evidence that dry needle – evoked inactivation of a primary ( key ) MTrP inhibits the activity in satellite MTrPs situated in its zone of pain referral . This supports the concept that activity in a primary MTrP leads to the development of activity in satellite MTrPs and the suggested spinal cord mechanism responsible for this phenomenon |
11,166 | 31,824,935 | Compared to the latter , hydrogel dressings associated with a significantly shortened healing time of degree II burn ( superficial and deep ) wounds , diabetic foot ulcers , traumatic skin injuries , radioactive skin injuries , dog bites , and body surface ulcers .
In addition , hydrogel dressing obviously increased the cure rate of diabetic foot ulcers , surgical wounds , dog bites , and body surface ulcers .
Moreover , hydrogel dressing significantly relieved pain in degree II burn ( superficial and deep ) wounds , traumatic skin injuries , and laser treatment-induced wounds .
However , no significant differences obtained between hydrogel and non-hydrogel dressings in the healing time of surgical wounds , the cure rate of in patients ' pressure ulcers , and phlebitis ulcers .
This comprehensive systematic review and meta- analysis of the available evidence reveals that the application of hydrogel dressings advances the healing of various wound types and effectively alleviates the pain with no severe adverse reactions .
These results strongly indicate that hydrogel products are effective and safe in wound management | The purpose of this systematic review and meta- analysis is to assess the clinical effectiveness and safety of the medical hydrogel dressings used in skin wounds and therefore to weight the evidence for their clinical application . | : In recent years , skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements . This review details the pioneering work of numerous investigators that led to the following precursors of tissue-engineered skin replacement : cultured autologous keratinocyte grafts , cultured allogeneic keratinocyte grafts , autologous/allogeneic composites , acellular collagen matrices , and cellular matrices . It also discusses the rationale for the development of the newer products and describes the technical advances leading to the development of Apligraf , a tissue-engineered human skin product BACKGROUND Burn-induced hypertrophic scars are disfiguring and can be associated with severe and intractable pruritus . No effective treatment modalities are currently available for symptomatic control of pruritus for most patients . We assessed the effect of the Antipruritic Hydrogel ( CQ-01 ) in the symptomatic treatment of severe and intractable pruritus associated with burn-induced hypertrophic scars in a prospect i ve , multicenter , controlled trial . METHODS A pilot study was conducted in healthy adult volunteers to identify the most appropriate hydrogel formulation . A selected preparation called Chongqing No. 1 ( CQ-01 ; a guar gum-based hydrogel impregnated with peppermint oil , menthol , and methyl salicylate by a nanoemulsion ) , showed an excellent symptomatic relief in an exploratory study in 2 patients with intractable pruritus . A statistically powered , prospect i ve , multicenter , controlled study was then conducted in 74 patients to evaluate the efficacy and safety of a 24-h application of CQ-01 compared to a gel control and a negative control on three separate areas in each patient . Symptom assessment was based on our visual analog JW scale ( ranging from 0 to 100 ) at baseline and various time points up to 7 days after application . Follow-up studies were conducted to determine the reproducibility of CQ-01 in repeated applications . RESULTS Of the 74 enrolled subjects , the only observed adverse event was skin irritation reported in 6 patients ( 8 % ) and resolved shortly after gel removal . Compared to the baseline , the gauze negative control had a mean JW score reduction of 7 ; while the gel control and CQ-01 had a drop of 18 ( p<0.001 ) and 36 ( p<0.001 ) , respectively . The CQ-01 clinical effect was significant for up to 3 days and waned slowly from 3 to 7 days . There was no statistical correlation between the treatment response and any of the demographic , patient or burn-related factors . Further studies showed a trend that repeated applications might be more effective , suggesting the absence of tachyphylaxis . CONCLUSIONS This prospect i ve , multicenter , controlled study showed that this novel hydrogel CQ-01 is safe and provides significant symptomatic relief for severe and intractable pruritus associated with hypertrophic scars , an unmet medical need for these patients . This effect is independent of the etiology of the burn trauma , extent of the scarring , and duration of the scar formation In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies |
11,167 | 31,939,202 | Emerging evidence shows that BCM significantly improves the ability to get up unassisted from the floor , as well as mobility with reduced fall incidence in older people .
Furthermore , it can potentially reduce fear of falling .
BCM provides a promising intervention in fall-related recovery strategies for older adults and is most effective when offered to older adults at risk of falling . | Being unable to “ get up from the floor ” is a risk factor and predictor of serious fall-related injuries in older age ; however , floor-rise training ( FRT ) is not widely used .
The backward chaining method ( BCM ) is a success-oriented , step-by-step form of FRT .
This systematic review aim ed to evaluate the impact of BCM on physical and psychological outcome measures , and its clinical application . | Background Motor imagery ( MI ) when combined with physiotherapy can offer functional benefits after stroke . Two MI integration strategies exist : added and embedded MI . Both approaches were compared when learning a complex motor task ( MT ) : ' Going down , laying on the floor , and getting up again ' . Methods Out patients after first stroke participated in a single-blinded , r and omised controlled trial with MI embedded into physiotherapy ( EG1 ) , MI added to physiotherapy ( EG2 ) , and a control group ( CG ) . All groups participated in six physiotherapy sessions . Primary study outcome was time ( sec ) to perform the motor task at pre and post-intervention . Secondary outcomes : level of help needed , stages of MT-completion , independence , balance , fear of falling ( FOF ) , MI ability . Data were collected four times : twice during one week baseline phase ( BL , T0 ) , following the two week intervention ( T1 ) , after a two week follow-up ( FU ) . Analysis of variance was performed . Results Thirty nine out patients were included ( 12 females , age : 63.4 ± 10 years ; time since stroke : 3.5 ± 2 years ; 29 with an ischemic event ) . All were able to complete the motor task using the st and ardised 7-step procedure and reduced FOF at T0 , T1 , and FU . Times to perform the MT at baseline were 44.2 ± 22s , 64.6 ± 50s , and 118.3 ± 93s for EG1 ( N = 13 ) , EG2 ( N = 12 ) , and CG ( N = 14 ) . All groups showed significant improvement in time to complete the MT ( p < 0.001 ) and degree of help needed to perform the task : minimal assistance to supervision ( CG ) and independent performance ( EG1 + 2 ) . No between group differences were found . Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU . The kinaesthetic indicator increased from T1 to FU . Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks . Conclusions Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently . Based on their baseline level CG had the highest potential to improve outcomes . A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy .Trial Registration Clinical Trials.gov : Objectives To describe the incidence and extent of lying on the floor for a long time after being unable to get up from a fall among people aged over 90 ; to explore their use of call alarm systems in these circumstances . Design 1 year follow-up of participants in a prospect i ve cohort study of ageing , using fall calendars , phone calls , and visits . Setting Participants ’ usual place of residence ( own homes or care homes ) , mostly in Cambridge . Participants 90 women and 20 men aged over 90 ( n=110 ) , surviving participants of the Cambridge City over-75s Cohort , a population based sample . Main outcome measures Inability to get up without help , lying on floor for a long time after falling , associated factors ; availability and use of call alarm systems ; participants ’ views on using call alarms to summon help if needed after falling . Results In one year ’s intensive follow-up , 54 % ( 144/265 ) of fall reports described the participant as being found on the floor and 82 % ( 217/265 ) of falls occurred when the person was alone . Of the 60 % who fell , 80 % ( 53/66 ) were unable to get up after at least one fall and 30 % ( 20/66 ) had lain on the floor for an hour or more . Difficulty in getting up was consistently associated with age , reported mobility , and severe cognitive impairment . Cognition was the only characteristic that predicted lying on the floor for a long time . Lying on the floor for a long time was strongly associated with serious injuries , admission to hospital , and subsequent moves into long term care . Call alarms were widely available but were not used in most cases of falls that led to lying on the floor for a long time . Comments from older people and carers showed the complexity of issues around the use of call alarms , including perceptions of ir relevance , concerns about independence , and practical difficulties . Conclusions Lying on the floor for a long time after falling is more common among the “ oldest old ” than previously thought and is associated with serious consequences . Factors indicating higher risk and comments from participants suggest practical implication s. People need training in strategies to get up from the floor . Work is needed on access and activation issues for design of call alarms and information for their effective use . Care providers need better underst and ing of the perceptions of older people to provide acceptable support services Frequent or recurrent fallers are more likely to have chronic medical conditions and physiological impairments , exhibit functional decline and have poor outcomes , than single fallers [ 1 ] . Fractures are also more common in recurrent fallers than single fallers [ 2 ] . Modern surgery for hip fracture can no longer improve on its outcomes [ 3 ] and therefore , effective prevention of falls [ 4 , 5 ] is the key to preventing disability and death . There is still no published evidence that a single intervention ( tailored group exercise ) can prevent falls or injuries in a high risk group of frequent fallers . This r and omised controlled trial ( RCT ) aim ed to investigate the impact of a 36 week individualised and tailored group and home exercise intervention , compared with a control intervention , in reducing falls and injuries in communitydwelling , independent-living , frequent falling women aged 65 years and over . Preliminary results have been published in abstract form [ 6 ] . The primary outcome was falls and fallrelated injuries . The secondary outcome was the number of frequent fallers who had died , had moved into residential care or were in hospital compared with the group they were in OBJECTIVES To determine the effect of a 2-week ( six-session ) training intervention to improve the ability of disabled older adults to rise from the floor . DESIGN Prospect i ve intervention trial . SETTING Congregate housing in Michigan . PARTICIPANTS Subjects aged 65 and older who admitted to requiring assistance ( such as from a person , equipment , or device ) in performing at least one of the following mobility-related activities of daily living : transferring , walking , bathing , and toileting . INTERVENTION Participants were r and omly allocated to individual training ( n = 17 , mean age 81 ) in strategies to rise from the floor ( using for example , certain key intermediate body positions ) or a control chair-based flexibility intervention ( n = 18 , mean age 80 ) . MEASUREMENTS At baseline and postintervention , residents were queried regarding their rise difficulty ( difficulty scale ) and symptoms ( symptoms scale ) associated with the rise and were tested in their ability to perform timed floor-rise tasks . These tasks varied in starting position ( supine vs all fours ) and in use of a support to assist in rising ( no support , use of an end table , use of a chair ) . RESULTS Using baseline performance as the covariate , by analysis of covariance ( ANCOVA ) , the training group showed a significant ( P < .05 ) improvement in mean number of rise tasks completed ( baseline mean 6.6 , postintervention mean 7.3 ) versus essentially no improvement in the controls . Similarly , by ANCOVA , the training group ( compared with controls ) showed a significant ( P < .05 ) improvement on the difficulty and symptoms scales . There was no intervention effect for rise time . CONCLUSIONS A short-term , strategy -based intervention improved floor-rise ability and perceived difficulty and symptoms associated with the rise . This approach , focusing on key intermediate body positions , may be useful in training floor-rise skills , particularly in older adults at risk for falls OBJECTIVES To evaluate the safety and acceptability of a novel 8-week intervention integrating exercise , exposure therapy , cognitive restructuring , and a home safety evaluation , conducted by a physical therapist , in reducing fear of falling and activity avoidance . To collect preliminary evidence of efficacy . DESIGN R and omized pilot study comparing the intervention to time- and attention-equivalent fall prevention education . SETTING Participants ' homes . PARTICIPANTS 42 older adults with disproportionate fear of falling ( high fear , low to moderate objective fall risk ) . MEASUREMENTS Falls Efficacy Scale-International , modified Activity Card Sort , satisfaction , falls . RESULTS Relative to education , the intervention reduced fear of falling ( d = 1.23 ) and activity avoidance ( d = 1.02 ) at 8 weeks , but effects eroded over a 6-month follow-up period . The intervention did not increase falls , and participants rated the exercise , exposure therapy , and non-specific elements as most helpful . CONCLUSIONS An integration of exercise and exposure therapy may help older adults with disproportionate fear of falling , but modifications to the intervention or its duration may be needed to maintain participants ' gains BACKGROUND Depression and cognitive functioning have a negative impact on functional recovery after hip fracture surgery in older people , and the same has been suggested for pain and fear of falling . These variables , however , have never been studied together , nor has the timing of psychiatric assessment been taken into account . METHOD Two parallel , r and omized controlled trials were undertaken aim ing to prevent and treat depression after hip fracture surgery in older people . Multiple logistic regression analyses corrected for age and pre-morbid level of functioning were performed to evaluate the effect of depressive symptoms ( 15-item Geriatric Depression Scale , GDS ) , pain ( Wong-Baker pain scale ) , cognitive functioning ( Mini-mental State Examination , MMSE ) and fear of falling ( Modified Falls Efficacy Scale , MFES ) within 2 weeks after surgery and 6 weeks later on functional recovery at 6 months . Main outcome measures were performance-based measures ( up- and -go test , gait test , functional reach ) and the self-report Sickness Impact Profile ( SIP ) question naire to assess the impact of the hip fracture on activities of daily living ( ADL ) . RESULTS Two hundred and ninety-one patients participated and outcome measures for 187 ( 64 % ) patients were available at 6 months . All mental health variables interfered with functional recovery . However , in the final multivariate model , cognitive functioning and fear of falling assessed 6 weeks after surgery consistently predicted functional recovery , whereas pain and depressive symptoms were no longer significant . CONCLUSION Fear of falling and cognitive functioning may be more important than pain and depression to predict functional recovery after hip fracture surgery . Rehabilitation strategies should take this into account BACKGROUND To determine the respective efficacy of two different instruction programmes design ed to aid the elderly in rising unassisted after an incidental fall . METHODS The 12-week study covered 120 recent fallers ( age range : 80 - 90 years ) r and omly split into two study groups : Group I ( 61 subjects ; 41F , 20 M ) , Group II ( 59 subjects 37F , 22 M ) . Group I followed a programme combining safe postural shifts and the backward-chaining method , whereas Group II ( controls ) took part in conventional training to rise unassisted after a fall . The duration of the instructional programmes was 12 weeks . The Timed " Up & Go " and Tinetti tests were applied at baseline and on completion of the programmes to assess individual ability to rise unassisted after an incidental fall . The results in both groups were assessed with the t-Student test and the Wilcoxon test . RESULTS Statistically significant improvements were only noted in Group I ( p<0.05 ) in the Timed " Up & Go " test score ( 27 vs. 20 sec. ) , Tinetti score ( 40 % of subjects ) , as well as in individual ability to rise unassisted after a fall ( 20%-40 % ) . No statistically quantifiable improvements were observed in the control group . CONCLUSIONS The instructional programme involving the backward-chaining method enhances individual functional capabilities , as well as tangibly aids the elderly in rising unassisted after an incidental fall 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 and aims : Older age , higher morbidity and lower functional capacity are associated with fall injuries . Inability to get up from the floor is associated with older age , higher morbidity and lower functional capacity . The purpose of this study was to assess the concurrent and predictive validity of the ability of elderly women to get up from lying on the floor . Methods : In a r and om sample of 307 women aged 75 years and over ( mean 80.8 years , response rate 74.5 % ) living in the community , baseline registration s of ability to get up from lying on the floor , health and function were recorded . Serious fall injuries during the subsequent year served as the outcome . Results : 240 ( 78.2 % ) managed to get up independently . The highest independent association was with items primarily related to mobility , e.g. , ability to climb steps and performance on the Timed Up & Go test ( TUG ) . However , arthrosis of the hip and difficulty with walking indoors were among the variables independently associated with the ability to get up from lying on the floor . During the follow-up year , 50.5 % experienced falls , of which one in four result ed in serious injury and one in eight in a fracture . The ability to get up from lying on the floor was a significant predictor of serious fall-related injury ( OR 2.1 ) . Among those who experienced a fall , the risk of injury was markedly higher for those unable to rise ( OR 3.7 ) . The positive predictive value of being unable to rise for serious injury was 0.30 , indicating that nearly one out of three of the elderly women with such problems are predicted to experience a serious fall-related injury during the following 12 months . Conclusions : The test “ get up from lying on the floor ” is a marker of failing health and function in the elderly and a significant predictor of serious fall injuries Abstract Purpose : To review available evidence on older people ’s ability to get up off the floor independently and determine the effectiveness of interventions to improve older adults ’ ability to rise from the floor . Material s and methods : Seven data bases were search ed between January 1975 and June 2018 . Eligibility criteria included : people aged ≥60 ; interventions to improve strength/function including ability to get up off the floor ( for intervention studies ) ; comparison groups ( for r and omized and nonr and omized controlled trials ) ; outcome : quantitative or qualitative evaluation of ability to get up off the floor . Selection of the studies was undertaken in three stages : ( 1 ) titles and abstract s were scanned by one review er , ( 2 ) full abstract screening by one review er , and ( 3 ) articles read in full by two review ers . Results of all articles are summarized and r and omized controlled trials ( RCT ) ( where possible ) were analyzed by meta- analysis to determine intervention effectiveness . Results : Forty-one studies met inclusion criteria . For each of the RCTs that utilized resistance training and /or teaching the skill , a reduction in time to get up off the floor were reported . However , meta-analyses of all RCT interventions indicated no significant change in time for older people to get up off the floor independently with intervention ( MD : –0.43[–1.38 , 0.51 ] ) . Sub-analyses of interventions utilizing resistance training showed an improvement trending towards significance ( MD : –0.81[–1.72 , 0.09 ] ) . Heterogeneity between studies was high , therefore results should be viewed with some caution . Conclusions : Resistance training interventions may improve older people ’s ability to rise from the floor unassisted . However , knowledge of specific techniques to get up and the effect of simply practicing the task of getting off the floor need to be further explored . Implication for rehabilitation One in three older people living in the community fall each year One aspect of falling that is often overlooked is whether the older person can get themselves up off the floor independently or do they have to wait for assistance . Interventions that include resistance training may help the older person to be able to get up by themselves |
11,168 | 32,194,194 | Docosahexaenoic ( DHA ) and vaccenic acids were significantly lower and higher respectively in MCI relative to controls .
Total fatty acids were 27.2 % lower in AD relative to controls , and this was reflected almost uniformly in all specific fatty acids in AD .
Changes to plasma/serum fatty acids were identified in both MCI and AD relative to age and gender matched controls .
Differences were greatest in AD , in both total number of fatty acids significantly altered , and the degree of change .
Docosahexaenoic acid was lower in both MCI and AD , suggesting that it may be a driver of pathology | Plasma fatty acids have been reported to be dysregulated in mild cognitive impairment ( MCI ) and Alzheimer 's disease ( AD ) , though outcomes are not always consistent , and subject numbers often small .
Our aim was to use a meta- analysis and systematic review approach to identify if plasma fatty acid dysregulation would be observed in case control studies of AD and MCI . | BACKGROUND Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies , but there is limited study of whether this type of fat protects against Alzheimer disease . OBJECTIVE To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease . DESIGN Prospect i ve study conducted from 1993 through 2000 , of a stratified r and om sample from a geographically defined community . Participants were followed up for an average of 3.9 years for the development of Alzheimer disease . PATIENTS A total of 815 residents , aged 65 to 94 years , who were initially unaffected by Alzheimer disease and completed a dietary question naire on average 2.3 years before clinical evaluation of incident disease . MAIN OUTCOME MEASURES Incident Alzheimer disease diagnosed in a structured neurologic examination by means of st and ardized criteria . RESULTS A total of 131 sample participants developed Alzheimer disease . Participants who consumed fish once per week or more had 60 % less risk of Alzheimer disease compared with those who rarely or never ate fish ( relative risk , 0.4 ; 95 % confidence interval , 0.2 - 0.9 ) in a model adjusted for age and other risk factors . Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease , as was intake of docosahexaenoic acid ( 22:6n-3 ) . Eicosapentaenoic acid ( 20:5n-3 ) was not associated with Alzheimer disease . The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions . CONCLUSION Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease BACKGROUND Emerging evidence suggests that docosahexaenoic acid ( DHA , 22:6n-3 ) , the principal omega-3 ( n-3 ) fatty acid in brain gray matter , positively regulates cortical metabolic function and cognitive development . However , the effects of DHA supplementation on functional cortical activity in human subjects are unknown . OBJECTIVE The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects . DESIGN Healthy boys aged 8 - 10 y ( n = 33 ) were r and omly assigned to receive placebo or 1 of 2 doses of DHA ( 400 or 1200 mg/d ) for 8 wk . Relative changes in cortical activation patterns during sustained attention at baseline and endpoint were determined by functional magnetic resonance imaging . RESULTS At 8 wk , erythrocyte membrane DHA composition increased significantly from baseline in subjects who received low-dose ( by 47 % ) or high-dose ( by 70 % ) DHA but not in those who received placebo ( -11 % ) . During sustained attention , both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group , and the low-dose and high-dose DHA groups had greater decreases in the occipital cortex and cerebellar cortex , respectively . Relative to low-dose DHA , high-dose DHA result ed in greater decreases in activation of bilateral cerebellum . The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation and was inversely correlated with reaction time , at baseline and endpoint . CONCLUSION Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys . This trial was registered at clinical trials.gov as NCT00662142 Background : Dietary fish oils , rich in long-chain n-3 ( ω-3 ) fatty acids ( FAs ) [ e.g. , docosahexaenoic acid ( DHA , 22:6n-3 ) and eicosapentaenoic acid ( EPA , 20:5n-3 ) ] , modulate inflammatory reactions through various mechanisms , including gene expression , which is measured as messenger RNA concentration . However , the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation , which controls messenger RNA generation-are poorly described . Objective : We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes ( PBLs ) and the relation to plasma EPA and DHA concentrations in Alzheimer disease ( AD ) patients . Design : In the present study , DNA methylation in four 5'-cytosine-phosphate-guanine-3 ' ( CpG ) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients ( 30 given the n-3 FA preparation and 33 given placebo ) as an estimation of the global DNA methylation in blood cells . Patients originated from the r and omized , double-blind , placebo-controlled OmegAD study , in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA ( the n-3 FA group ) or placebo daily for 6 mo . Results : At 6 mo , the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations ( 2.6- and 3.5-fold ) , as well as decreased methylation in 2 out of 4 CpG sites ( P < 0.05 for all ) , respectively . This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration ( r = -0.25 , P = 0.045 ; and r = -0.26 , P = 0.041 , respectively ) , but not to changes in plasma DHA concentration , and were not related to apolipoprotein E-4 allele frequency . Conclusion : Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs . Our data may be of importance in measuring various effects of marine oils , including gene expression , in patients with AD and in other patients taking n-3 FA supplements . This trial was registered at clinical trials.gov as NCT00211159 Given evidence that eicosapentaenoic acid ( EPA ) , docosahexaenoic acid ( DHA ) , and anthocyanin-rich blueberries provide neurocognitive benefit , we investigated long-term supplementation in older adults with cognitive complaints . In a 24-week r and omized , double-blind , placebo-controlled trial , elderly men and women received daily fish oil ( FO ) or blueberry ( BB ) or both . Diet records confirmed that participants reduced background consumption of EPA , DHA , and anthocyanins as prescribed . Erythrocyte EPA + DHA composition increased in the FO groups ( p = 0.0001 ) . Total urinary anthocyanins did not differ between the groups after supplementation but glycoside and native ( food ) forms increased only in the BB-supplemented groups . The FO ( p = 0.03 ) and BB ( p = 0.05 ) groups reported fewer cognitive symptoms , and the BB group showed improved memory discrimination ( p = 0.04 ) , indicating that supplementation improved cognition . Cognitive benefit in the BB group was associated with the presence of urinary anthocyanins reflecting recent BB intake but not with anthocyanin metabolites . However , combined FO + BB treatment was not associated with cognitive enhancement as expected BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Background / objectives to investigate the effects of a 3-year multidomain lifestyle intervention , omega-3 supplementation or both on physical activity ( PA ) in older adults with subjective memory complaints . Design / setting s/subjects the Multidomain Alzheimer Preventive Trial was a 3-year r and omised controlled trial that enroled 1,680 community-dwelling adults aged 70 years or over , with subjective memory complaints . Participants were r and omised to omega-3 supplementation ( total daily dose of 800 mg docosahexanoic acid and up to 225 mg eicosapentanoic acid ) , multidomain intervention ( nutritional and exercise counselling and cognitive training ) , omega-3 plus multidomain intervention or placebo with usual care . Methods PA was assessed using a self-reported question naire . From this , global moderate-to-vigorous PA , leisure-time PA , non-leisure-time PA and light PA were measured in metabolic equivalent tasks-minutes per week ( MET-min/week ) . Results in the multidomain groups , participants significantly increased their moderate-to-vigorous and leisure-time PA at 6 months ( ≥300 MET-min/week for both in the multidomain groups ; P ≤ 0.002 ) before returning to baseline by the end of the trial . Activity in the placebo/usual care and omega-3/usual care groups declined overtime . Between-group differences remained significant for both multidomain groups for leisure-time physical activity at 2- and 3-year follow-ups . Compared to placebo/usual care , interventions had no significant effects on non-leisure-time PA and light PA . Omega-3 supplementation alone had no effects on PA . Conclusions a multidomain intervention focused on cognitive training , and nutritional and PA counselling increased PA in the short-term and limited its decline in the long-term among older adults with memory complaints . Clinical Trials.gov- Registration number : NCT0067268 Background Cognitive decline has been reported following cardiac surgery , leading to great interest in interventions to minimize its occurrence . Long-chain n-3 ( ω-3 ) polyunsaturated fatty acids ( PUFAs ) have been associated with less cognitive decline in observational studies , yet no trials have tested the effects of n-3 PUFAs on cognitive decline after surgery . Objective We sought to determine whether perioperative n-3 PUFA supplementation reduces postoperative cognitive decline in patients postcardiac surgery . Methods The study comprised a r and omized , double-blind , placebo-controlled , multicenter , clinical trial conducted on cardiac surgery recipients at 9 tertiary care medical centers across the United States . Patients were r and omly assigned to receive fish oil ( 1-g capsules containing ≥840 mg n-3 PUFAs as ethyl esters ) or placebo , with preoperative loading of 8 - 10 g over 2 - 5 d followed postoperatively by 2 g/d until hospital discharge or postoperative day 10 , whichever came first . Global cognition was assessed using in-person testing over 30 d with the Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) ( primary outcome ) , Mini-Mental State Exam ( secondary outcome ) , and Trails A and B ( secondary outcome ) tests . All end points were prespecified . Statistical methods were employed , including descriptive statistics , logistic regression , and various sensitivity analyses . Results A total of 320 US patients were enrolled in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation ( OPERA ) Cognitive Trial ( OCT ) , a sub study of OPERA . The median age was 62 y ( IQR 53 , 70 y ) . No differences in global cognition were observed between placebo and fish oil groups at day 30 ( P = 0.32 ) for the primary outcome , a composite neuropsychological RBANS score . The population demonstrated resolution of initial 4-d cognitive decline back to baseline function by 30 d on the RBANS . Conclusion Perioperative supplementation with n-3 PUFAs in cardiac surgical patients did not influence cognition ≤30 d after discharge . Modern anesthetic , surgical , and postoperative care may be mitigating previously observed long-term declines in cognitive function following cardiac surgery . This trial was registered at clinical trials.gov as NCT00970489 Background Higher docosahexaenoic acid ( DHA ) intake is inversely correlated with relative risk of Alzheimer ’s disease . The potential benefits of DHA supplementation in people with mild cognitive impairment ( MCI ) have not been fully examined . Objective Our study aim ed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (Aβ)-mediated autophagy in elderly subjects with MCI . Methods This was a r and omised , double-blind , placebo-controlled trial in Tianjin , China . A total of 240 individuals with MCI were identified and r and omly divided into intervention ( DHA 2 g/day , n=120 ) and control ( corn oil as placebo , n=120 ) groups . Cognitive function and blood Aβ-related biomarkers were measured at baseline , 6 , 12 , 18 and 24 months . Data were analysed using generalised estimating equation . Results A total of 217 participants ( DHA : 109 , placebo : 108 ) completed the trial . During the follow-up , scores of full-scale IQ , verbal IQ and subdomains of information and digit span were significantly higher in the intervention group than the convention group ( p<0.05 ) . In the intervention group , blood Aβ-42 level and expression of Aβ protein precursor mRNA were decreased ( p<0.05 ) , while Beclin-1 and LC3-II levels and expression of LC3-II mRNA were increased ( p<0.05 ) . Conclusion Daily oral DHA supplementation ( 2 g/day ) for 24 months may improve cognitive function and change blood biomarker-related Aβ-mediated autophagy in people with MCI . Larger longer-term confirmatory studies are warranted . Trial registration number ChiCTR-IOR-15006058 BACKGROUND Dietary fish or fish oil rich in n-3 fatty acids ( n-3 FAs ) , eg , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , ameliorate inflammatory reactions by various mechanisms . Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations , few have addressed the effects of n-3 FAs preparations with DHA as the main FA . OBJECTIVE The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells ( P BMC s ) . DESIGN In a r and omized , double-blind , placebo-controlled trial , 174 Alzheimer disease ( AD ) patients received daily either 1.7 g DHA and 0.6 g EPA ( n-3 FAs group ) or placebo for 6 mo . In the present study blood sample s were obtained from the 23 first r and omized patients , and P BMC s were isolated before and after 6 mo of treatment . RESULTS Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group . This group also showed significant decreases of interleukin (IL)-6 , IL-1beta , and granulocyte colony-stimulating factor secretion after stimulation of P BMC s with lipopolysaccharide . Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects . Reductions of IL-1beta and IL-6 were also significantly correlated with each other . In contrast , this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha , IotaL-8 , IL-10 , and granulocyte-macrophage colony-stimulating factor secretion . CONCLUSION AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA ( and EPA ) , which were associated with reduced release of IL-1beta , IL-6 , and granulocyte colony-stimulating factor from P BMC s. This trial was registered at clinical trials.gov as NCT00211159 Objectives Elevated total plasma homocysteine is a risk factor for Alzheimer ’s disease ( AD ) and there is some evidence that omega-3 polyunsaturated fatty acids ( n-3 PUFAs ) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies . Hence we investigated the relationship between total plasma homocysteine and cortical β-amyloid ( Aβ ) in older adults at risk of dementia . The role of erythrocyte membrane n-3 PUFAs ( omega 3 index ) on this relationship was also explored . Design This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial ( MAPT ) ; a r and omised controlled trial . Setting French community dwellers aged 70 or over reporting subjective memory complaints , but free from a diagnosis of clinical dementia . Participants Individuals were from the MAPT trial ( n = 177 ) with data on total plasma homocysteine at baseline and cortical Aβ load . Measurements Cortical-to-cerebellar st and ard uptake value ratios were assessed using [ 18F ] florbetapir positron emission tomography ( PET ) . Total baseline plasma homocysteine was measured using an enzymatic cycling assay . Baseline omega 3 index was measured using gas chromatography . Cross-sectional associations were explored using adjusted multiple linear regression models . Results We found that total baseline plasma homocysteine was not significantly associated with cortical Aβ as demonstrated using multiple linear regression models adjusted for age , sex , education , cognitive status , time interval between baseline and PET-scan , omega-3 index , MAPT group allocation and Apolipoprotein E ε4 status ( B-coefficient -0.001 , 95 % CI : -0.008,0.006 , p = 0.838 ) . Exploratory analysis showed that homocysteine was however significantly associated with cortical Aβ in subjects with low baseline omega-3 index ( < 4.72 % ) after adjustment for Apolipoprotein E ε4 status ( B-coefficient 0.041 , 95 % CI : 0.017,0.066 , p = 0.005 , n = 10 ) , but not in subjects with a high baseline omega-3 index ( B-coefficient -0.010 , 95 % CI : -0.023,0.003 , p = 0.132 , n = 66 ) . Conclusions The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aβ warrants further investigation A few studies have assessed the association between omega-3 polyunsaturated fatty acids ( n-3 PUFA ) and cognitive impairment ( CI ) in very old adults . The aim of this study was to evaluate the effect of a multinutrient supplementation rich in n-3 PUFA on the cognitive function in an institutionalized ≥75-year-old population without CI or with mild cognitive impairment ( MCI ) . A multicenter placebo-controlled double-blind r and omized trial was conducted between 2012 and 2013 . Cognitive function was assessed at baseline and after one year using 4 neuropsychological tests . Nutritional status was assessed using Mini Nutritional Assessment ( MNA ) . Interaction between Mini-Mental State Examination ( MMSE ) score and nutritional status were analyzed using linear regression models . A total of 99 participants were r and omized to receive placebo or pills rich in n-3 PUFA . After 1-year follow-up , both groups decreased their MMSE score ( -1.18 , SD:0 . 53 and -0.82 , SD:0 . 63 , p = 0.67 for the control and the intervention group respectively ) . The memory subscale of the MMSE showed an improvement ( + 0.26 , SD:0.18 ) in the intervention group against a worsening in the control group ( -0.11 , SD : 0.14 ; p = 0.09 for differences between groups ) . Patients at intervention group with normal nutritional status ( MNA ≥24 ) showed an improvement in the MMSE ( + 1.03 , p = 0.025 for differences between 1-y and baseline measurements ) against a worsening in the group with malnutrition ( MNA<24 ) ( -0.4 , p = 0.886 for differences between 1-y and baseline ; p of interaction p = 0.05 ) . Supplementation with n-3 PUFA did not show an improvement in the global cognitive function in institutionalized elderly people without CI or with MCI . They only suggest an apparent improvement in memory loss if previously they were well nourished Summary Background Nutrition is an important modifiable risk factor in Alzheimer 's disease . Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer 's disease dementia . LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer 's disease . Here , we report the 24-month results of the trial . Methods LipiDiDiet was a 24-month r and omised , controlled , double-blind , parallel-group , multicentre trial ( 11 sites in Finl and , Germany , the Netherl and s , and Sweden ) , with optional 12-month double-blind extensions . The trial enrolled individuals with prodromal Alzheimer 's disease , defined according to the International Working Group (IWG)-1 criteria . Participants were r and omly assigned ( 1:1 ) to active product ( 125 mL once-a-day drink containing Fortasyn Connect ) or control product . R and omisation was computer-generated central ly in blocks of four , stratified by site . All study personnel and participants were masked to treatment assignment . The primary endpoint was change in a neuropsychological test battery ( NTB ) score . Analysis was by modified intention to treat . Safety analyses included all participants who consumed at least one study product dose . This trial is registered with the Dutch Trial Register , number NTR1705 . Findings Between April 20 , 2009 , and July 3 , 2013 , 311 of 382 participants screened were r and omly assigned to the active group ( n=153 ) or control group ( n=158 ) . Mean change in NTB primary endpoint was −0·028 ( SD 0·453 ) in the active group and −0·108 ( 0·528 ) in the control group ; estimated mean treatment difference was 0·098 ( 95 % CI −0·041 to 0·237 ; p=0·166 ) . The decline in the control group was less than the pre study estimate of −0·4 during 24 months . 66 ( 21 % ) participants dropped out of the study . Serious adverse events occurred in 34 ( 22 % ) participants in the active group and 30 ( 19 % ) in control group ( p=0·487 ) , none of which were regarded as related to the study intervention . Interpretation The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer 's disease . However , cognitive decline in this population was much lower than expected , rendering the primary endpoint inadequately powered . Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed . Further study of nutritional approaches with larger sample sizes , longer duration , or a primary endpoint more sensitive in this pre-dementia population , is needed . Funding European Commission 7th Framework Programme BACKGROUND No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline . We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention ( physical activity , cognitive training , and nutritional advice ) , alone or in combination , compared with placebo , on cognitive decline . METHODS The Multidomain Alzheimer Preventive Trial was a 3-year , multicentre , r and omised , placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco . Participants were non-demented , aged 70 years or older , and community-dwelling , and had either relayed a spontaneous memory complaint to their physician , limitations in one instrumental activity of daily living , or slow gait speed . They were r and omly assigned ( 1:1:1:1 ) to either the multidomain intervention ( 43 group sessions integrating cognitive training , physical activity , and nutrition , and three preventive consultations ) plus omega 3 polyunsaturated fatty acids ( ie , two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid ) , the multidomain intervention plus placebo , omega 3 polyunsaturated fatty acids alone , or placebo alone . A computer-generated r and omisation procedure was used to stratify patients by centre . All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment , but were unblinded to the multidomain intervention component . Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment . The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests ( free and total recall of the Free and Cued Selective Reminding test , ten Mini-Mental State Examination orientation items , Digit Symbol Substitution Test , and Category Naming Test ) in the modified intention-to-treat population . The trial was registered with Clinical Trials.gov ( NCT00672685 ) . FINDINGS 1680 participants were enrolled and r and omly allocated between May 30 , 2008 , and Feb 24 , 2011 . In the modified intention-to-treat population ( n=1525 ) , there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group . Between-group differences compared with placebo were 0·093 ( 95 % CI 0·001 to 0·184 ; adjusted p=0·142 ) for the combined intervention group , 0·079 ( -0·012 to 0·170 ; 0·179 ) for the multidomain intervention plus placebo group , and 0·011 ( -0·081 to 0·103 ; 0·812 ) for the omega 3 polyunsaturated fatty acids group . 146 ( 36 % ) participants in the multidomain plus polyunsaturated fatty acids group , 142 ( 34 % ) in the multidomain plus placebo group , 134 ( 33 % ) in the polyunsaturated fatty acids group , and 133 ( 32 % ) in the placebo group had at least one serious emerging adverse event . Four treatment-related deaths were recorded ( two in the multidomain plus placebo group and two in the placebo group ) . The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events . INTERPRETATION The multidomain intervention and polyunsaturated fatty acids , either alone or in combination , had no significant effects on cognitive decline over 3 years in elderly people with memory complaints . An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined , particularly in real-world setting s. FUNDING French Ministry of Health , Pierre Fabre Research Institute , Gerontopole , Exhonit Therapeutics , Avid Radiopharmaceuticals Arachidonic acid ( ARA ) is an n-6 PUFA and is thought to have an important role in various physiological and psychological functions . Recently , supplementation with ARA-enriched TAG was shown to improve age-related decreases in cognitive function in healthy elderly men . To investigate the influence of baseline serum ARA status on cognitive function and its improvement , we analyzed cognitive function stratified by serum ARA level . The stratified analysis was also conducted for the effects of ARA-enriched TAG supplementation on cognitive improvement . Cognitive function was evaluated by measuring event-related potentials ( ERPs ) , including P300 latency and amplitude . When participants were stratified by baseline serum ARA level , P300 latency was significantly longer and P300 amplitude was generally lower in the low-ARA group than in the high-ARA group . No significant difference in P300 components was observed when participants were stratified by serum levels of any other fatty acid . ARA-enriched TAG supplementation significantly shortened P300 latency and increased P300 amplitude in the low-ARA group , although no significant differences were observed in the high-ARA group . These findings suggest that lower serum ARA levels were associated with cognitive function in elderly men and that ARA-enriched TAG supplementation is more effective in improving cognitive function in healthy elderly men with low serum ARA levels than in those with high serum ARA levels BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment , particularly in those who eventually convert to Alzheimer disease . Plasma concentrations of omega-3 ( ω-3 ) fatty acids and homocysteine are associated with the development of brain atrophy and dementia . OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations ( eicosapentaenoic acid and docosahexaenoic acid ) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial ( VITACOG ) . DESIGN This retrospective analysis included 168 elderly people ( ≥70 y ) with mild cognitive impairment , r and omly assigned either to placebo ( n = 83 ) or to daily high-dose B vitamin supplementation ( folic acid , 0.8 mg ; vitamin B-6 , 20 mg ; vitamin B-12 , 0.5 mg ) ( n = 85 ) . The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later . The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations . RESULTS There was a significant interaction ( P = 0.024 ) between B vitamin treatment and plasma combined ω-3 fatty acids ( eicosapentaenoic acid and docosahexaenoic acid ) on brain atrophy rates . In subjects with high baseline ω-3 fatty acids ( > 590 μmol/L ) , B vitamin treatment slowed the mean atrophy rate by 40.0 % compared with placebo ( P = 0.023 ) . B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids ( < 390 μmol/L ) . High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group . CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids . It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status . The results highlight the importance of identifying subgroups likely to benefit in clinical trials . This trial was registered at www.controlled-trials.com as IS RCT N94410159 BACKGROUND N-3 fatty acids ( FA ) have an important role in brain development and function . However , there is conflicting evidence concerning the relationship between n-3 FA and dementia in older persons . METHODS In the Invecchiare in Chianti ( InCHIANTI ) study , we measured plasma FA by gas chromatography in 935 community-dwelling older persons r and omly extracted from the population of two towns near Florence , Italy . Cognitive impairment was measured using the Mini-Mental Status Examination . Participants who scored < /=26 underwent a detailed clinical and neuropsychological evaluation . The diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders , Third Revision ( DSM-III-R ) criteria . The population was divided in three groups : persons with normal cognitive function , persons with cognitive impairment not demented , and persons with dementia . RESULTS After adjustment for age , gender , education , body mass index , weight loss , smoking status , cholesterol and triglycerides levels , daily intake of alcohol , FA and total energy , cardiovascular disease , depression and other FA levels , participants with dementia had significantly lower n-3 FA levels ( 2.9 % vs 3.2 % ; p < .05 ) , particularly alpha-linolenic acid levels ( 0.34 % vs 0.39 % ; p < .05 ) , than did participants with normal cognitive function . CONCLUSIONS Dementia is associated with low plasma n-3 FA relative concentrations . The possibility that higher n-3 FA intake is associated with a lower risk of cognitive impairment should be further investigated in prospect i ve studies BACKGROUND Studies on the systemic availability of nutrients and nutritional status in Alzheimer 's disease ( AD ) are widely available , but the majority included patients in a moderate stage of AD . OBJECTIVE This study compares the nutritional status between mild AD out patients and healthy controls . METHODS A subgroup of Dutch drug-naïve patients with mild AD ( Mini-Mental State Examination ( MMSE ) ≥20 ) from the Souvenir II r and omized controlled study ( NTR1975 ) and a group of Dutch healthy controls were included . Nutritional status was assessed by measuring levels of several nutrients , conducting the Mini Nutritional Assessment ( MNA ® ) question naire and through anthropometric measures . RESULTS In total , data of 93 healthy cognitively intact controls ( MMSE 29.0 [ 23.0 - 30.0 ] ) and 79 very mild AD patients ( MMSE = 25.0 [ 20.0 - 30.0 ] ) were included . Plasma selenium ( p < 0.001 ) and uridine ( p = 0.046 ) levels were significantly lower in AD patients , with a similar trend for plasma vitamin D ( p = 0.094 ) levels . In addition , the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids . Mean MNA screening score was significantly lower in AD patients ( p = 0.008 ) , but not indicative of malnutrition risk . No significant differences were observed for other micronutrient or anthropometric parameters . CONCLUSION In non-malnourished patients with very mild AD , lower levels of some micronutrients , a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed . This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition A high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease . Cardiovascular disease has been associated with dementia . We investigated the association between fat intake and incident dementia among participants , age 55 years or older , from the population ‐based prospect i ve Rotterdam Study . Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food‐frequency question naire . At baseline and after an average of 2.1 years of follow‐up , we screened for dementia with a three‐step protocol that included a clinical examination . The risk of dementia at follow‐up ( RR [ 95 % CI ] ) was assessed with logistic regression . After adjustment for age , sex , education , and energy intake , high intakes of the following nutrients were associated with an increased risk of dementia : total fat ( RR = 2.4 [ 1.1–5.2 ] ) , saturated fat ( RR = 1.9 [ 0.9–4.0 ] ) , and cholesterol ( RR = 1.7 [ 0.9–3.2 ] ) . Dementia with a vascular component was most strongly related to total fat and saturated fat . Fish consumption , an important source of n‐3 polyunsaturated fatty acids , was inversely related to incident dementia ( RR = 0.4 [ 0.2–0.9 ] ) , and in particular to Alzheimer 's disease ( RR = 0.3 [ 0.1–0.9 ] ) . This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia , whereas fish consumption may decrease this risk Alteration of cerebral perfusion can be considered as a possible therapeutic target in mild cognitive impairment . This r and omized , placebo-controlled , double-blind proof-of-concept study assessed effects of omega-3 fatty acids on cerebral perfusion in patients with mild cognitive impairment . In thirteen patients ( omega : n=5 ; placebo : n=8 ) cerebral perfusion was measured before and after 26-weeks intervention within posterior cortical regions using magnetic resonance imaging . There was a medium effect of intervention on cerebral blood flow ( η2=0.122 ) and blood volume ( η2=0.098 ) . The omega group showed an increase in blood flow ( mean difference : 0.02 [ corresponds to 26.1 % ] , 95 % confidence interval:0.00 - 0.05 ) and blood volume ( mean difference : 0.08 [ corresponds to 18.5 % ] , 95 % confidence interval:0.01 - 0.15 ) , which was not observed in the placebo group . These preliminary findings suggest that omega-3 fatty acids supplementation may improve perfusion in cerebral regions typically affected in mild cognitive impairment . Regulation of perfusion may help to maintain brain structure and function and potentially delay conversion to dementia A r and omized trial ( VITACOG ) in people with mild cognitive impairment ( MCI ) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline . We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment . 266 participants with MCI aged ≥70 years were r and omized to B vitamins ( folic acid , vitamins B6 and B12 ) or placebo for 2 years . Baseline cognitive test performance , clinical dementia rating ( CDR ) scale , and plasma concentrations of total homocysteine , total docosahexaenoic and eicosapentaenoic acids ( omega-3 fatty acids ) were measured . Final scores for verbal delayed recall , global cognition , and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids , whereas scores in the placebo group were similar across these concentrations . Among those with good omega-3 status , 33 % of those on B vitamin treatment had global CDR scores > 0 compared with 59 % among those on placebo . For all three outcome measures , higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins , while eicosapentaenoic acid appeared less effective . When omega-3 fatty acid concentrations are low , B vitamin treatment has no effect on cognitive decline in MCI , but when omega-3 levels are in the upper normal range , B vitamins interact to slow cognitive decline . A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline . This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia . Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves ( 1991 - 1992 and 1996 - 1997 ) of the Canadian Study of Health and Aging . Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline . Results were adjusted for age , sex , education , smoking , alcohol intake , body mass index , history of cardiovascular disease , and apolipoprotein E e4 genotype . In the cross-sectional analysis , no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia . In the prospect i ve analysis , a higher eicosapentaenoic acid ( p < 0.01 ) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid ( p < 0.07 ) , omega-3 ( p < 0.04 ) and total polyunsaturated fatty acid ( p < 0.03 ) concentrations were found in dementia cases . These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia BACKGROUND Mammalian gut microbiota have been implicated in a variety of functions including the breakdown of ingested nutrients , the regulation of energy intake and storage , the control of immune system development and activity , and the synthesis of novel chemicals . Previous studies have shown that feeding mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce the ratio of Bacteroidetes-to-Firmicutes , while feeding hosts a fat-restricted diet increases this ratio . However , few studies have investigated the differential effects of fatty acid type on gut bacterial profile . METHODS Over a 14-week period , Mus musculus were fed a diet rich in omega-3 polyunsaturated fatty acids ( n-3 PUFAs ) , omega-6 polyunsaturated fatty acids ( n-6 PUFAs ) , or saturated fatty acids ( SFAs ) . Fecal pellets were collected before and after the treatment period from 12 r and omly selected mice ( 4 per treatment group ) . Bacterial DNA was extracted from the pellets and characterized by analysis of the hypervariable V3 region of the 16S rRNA . Nominal logistic regression models were used to assess shifts in microbial profile at the phylum and family levels in response to diet . RESULTS A significant decrease in the proportion of phylum Bacteroidetes species was observed for mice fed any of the three diets over time . However , the SFA-rich diet group showed a significantly greater decrease in Bacteroidetes proportion ( -28 % ) than did either the n-3 PUFA group ( -10 % ) or the n-6 PUFA group ( -12 % ) . At the family level , a significant decrease in proportion of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet , and a significant decrease in proportion of Lachnospiraceae was observed for mice fed the SFA-rich diet . There was no significant effect of diet type on body mass change . CONCLUSION Our results indicate that SFAs have stronger effects than PUFAs in shifting gut microbiota profiles toward those typical of obese individuals , and that dietary fatty acid saturation influences shifts in gut microbiota independently of changes in body mass |
11,169 | 32,353,082 | Conclusions Consistent identification of cost-effective and cost-saving interventions may help to reduce the DFU healthcare burden . | Background Diabetic foot ulcer ( DFU ) is a severe complication of diabetes and particularly susceptible to infection .
DFU infection intervention efficacy is declining due to antimicrobial resistance and a systematic review of economic evaluations considering their economic feasibility is timely and required .
Aim To obtain and critically appraise all available full economic evaluations jointly considering costs and outcomes of infected DFUs . | OBJECTIVE Determine the cost-effectiveness of extracellular matrix ( ECM ) relative to human fibroblast-derived dermal substitute ( HFDS ) on diabetic foot ulcer ( DFU ) wound closure . METHOD Outcomes data were obtained from a 12-week , r and omised , clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU . Patients were treated with either ECM or HFDS treatment . A two-state Markov model ( healed and unhealed ) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient . Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation ( primary outcome ) . The perspective of the analysis was that of the payer , specifically the Centers for Medicare and Medicaid Services . No cost discounting was performed because of the short duration of the study . RESULTS The study consisted of 26 patients , with 13 in each group . In the ECM group , 10 wounds closed ( 77 % ) , with an average closure time of 36 days ; 11 wounds closed in the HFDS group ( 85 % ) , with an average closure time of 41 days . There was no significant difference between these results ( p=0.73 ) . Over 12 weeks , the expected cost per DFU was $ 2522 ( £ 1634 ) for ECM and $ 3889 ( £ 2524 ) for HFDS . Patients treated with HFDS incurred total treatment costs that were approximately 54 % higher than those treated with ECM . Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $ 500 ( £ 325 ) . CONCLUSION In patients with DFU , ECM yielded similar clinical outcomes to HFDS but at a lower cost . Health-care providers should consider ECM as a cost-saving alternative to HFDS . DECLARATION OF INTEREST A.M. Gilligan , and C.R. Waycaster , are employees of Smith & Nephew Inc .. This study was funded by Smith & Nephew Inc .. A.L. L and sman , reports no conflicts of interest BACKGROUND Ulcers of the foot in people with diabetes mellitus are slow to heal and result in considerable cost and patient suffering . The prognosis is worst for ulcers of the heel . OBJECTIVE To assess both the clinical effectiveness and the cost-effectiveness of lightweight fibreglass casts in the management of heel ulcers . DESIGN A pragmatic , multicentre , parallel , observer-blinded r and omised controlled trial . A central r and omisation centre used a computer-generated r and om number sequence to allocate participants to groups . SETTING Thirty-five specialist diabetic foot secondary care centres in the UK . Those recruited were aged ≥ 18 years and had diabetes mellitus complicated by ulcers of the heel of grade s 2 - 4 on the National Pressure Ulcer Advisory Panel and European Pressure Ulcer Advisory Panel scale . PARTICIPANTS In total , 509 participants [ 68 % male , 15 % with type 1 diabetes mellitus , mean age 67.5 years ( st and ard deviation 12.4 years ) ] were r and omised 1 : 1 to the intervention ( n = 256 ) or the control ( n = 253 ) arm . The primary outcome data were available for 425 participants ( 212 from the intervention arm and 213 from the control arm ) and exceeded the total required ; attrition was 16.5 % . The median ulcer area at baseline was 275 mm2 [ interquartile range ( IQR ) 104 - 683 mm2 ] in the intervention group and 206 mm2 ( IQR 77 - 649 mm2 ) in the control group . There were no differences between the two groups at baseline in any parameter , neither in relation to the participant nor in relation to their ulcer . INTERVENTIONS The intervention group received usual care supplemented by the addition of an individually moulded , lightweight , fibreglass heel cast . The control group received usual care alone . The intervention phase continued either until the participant 's ulcer had healed ( maintained for 28 days ) or for 24 weeks , whichever occurred first . During this intervention phase , the participants were review ed every 2 weeks , and the fibreglass casts were replaced when they were no longer usable . MAIN OUTCOME MEASURES The primary outcome measure was ulcer healing ( confirmed by a blinded observer and maintained for 4 weeks ) within 24 weeks . Other outcome measures included the time taken for the ulcer to heal , the percentage reduction in the cross-sectional area , the reduction in local pain , amputation , survival and health economic analysis . The study was powered to define a difference in healing of 15 % ( 55 % intervention vs. 40 % control ) . RESULTS Forty-four per cent ( n = 94 ) of the intervention group healed within 24 weeks , compared with 37 % ( n = 80 ) of the control participants ( odds ratio 1.42 , 95 % confidence interval 0.95 to 2.14 ; p = 0.088 ) , using an intention-to-treat analysis . No differences were observed between the two groups for any secondary outcome . LIMITATIONS Although the component items of care were st and ardised , because this was a pragmatic trial , usual care was not uniform . There was some evidence of a small excess of adverse events in the intervention group ; however , non-blinded observers documented these events . There was no excess of adverse device effects . CONCLUSIONS There may be a small increase in healing with the use of a heel cast , but the estimate was not sufficiently precise to provide strong evidence of an effect . There was no evidence of any subgroup in which the intervention appeared to be particularly effective . A health economic analysis suggested that it is unlikely that the intervention represents good value for money . The provision of a lightweight heel cast may be of benefit to some individuals , but we have found no evidence to justify the routine adoption of this in clinical practice . FUTURE WORK It is unlikely that further study of this intervention will have an impact on usual clinical care , and so future efforts should be directed towards other interventions design ed to improve the healing of ulcers in this population . TRIAL REGISTRATION Current Controlled Trials IS RCT N62524796 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 21 , No. 34 . See the NIHR Journals Library website for further project information OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products , N-A , Inadine and Aquacel , for patients with diabetic foot ulcers , as well as the feasibility and consequences of less frequent dressing changes by health-care professionals . DESIGN A multicentre , prospect i ve , observer-blinded , parallel group , r and omised controlled trial , with three arms . SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK . PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic ( present for at least 6 weeks ) full-thickness foot ulcer ( on or below the malleoli ) not penetrating to tendon , periosteum or bone , and with a cross-sectional area between 25 and 2500 mm(2 ) . INTERVENTIONS Participants were r and omised 1:1:1 to treatment with one of N-A ( a non-adherent , knitted , viscose filament gauze ) , Inadine ( an iodine-impregnated dressing ) , both traditional dressings , or Aquacel , a newer product . MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24 . Secondary measures included time to healing , new ulcerations , major and minor amputations , and episodes of secondary infection . RESULTS A total of 317 patients were r and omised . After 88 withdrawals , 229 remained evaluable . A greater proportion of smaller ( 25 - 100 mm(2 ) ulcers healed within the specified time ( 48.3 % versus 37.3 % ; p = 0.048 ) . There was , however , no difference between the three dressings in terms of percentage healed by 24 weeks , or in the mean time to healing , whether analysed on the basis of intention to treat ( Inadine 44.4 % , N-A 38.7 % , Aquacel 44.7 % ; not significant ) or per protocol ( Inadine 55.2 % , N-A 59.4 % , Aquacel 63.0 % ; not significant ) . There was no difference in the quality of healing , as reflected in the incidence of recurrence within 12 weeks . Likewise , there was no difference in the incidence of adverse events , although a greater proportion of those r and omised to the non-adherent dressings were withdrawn from the study ( 34.9 % versus 29.1 % Aquacel and 19.4 % Inadine ; p = 0.038 ) . The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings ( mean cost per patient : N-A 14.85 pounds , Inadine 17.48 pounds , Aquacel 43.60 pounds ) . The higher cost of Aquacel was not offset by the fewer dressings required . There was no difference in measures of either generic or condition-specific measures of quality of life . However , there was a significant difference in the change in pain associated with dressing changes between the first and second visits , with least pain reported by those receiving non-adherent dressings ( p = 0.012 ) . There was no difference in the costs of professional time , and this may relate to the number of dressing changes undertaken by non-professionals . Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer , although this ranged from 22 % to 82 % between the different centres . CONCLUSIONS As there was no difference in effectiveness , there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service , thus generating potentially substantial savings . The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs . TRIAL REGISTRATION Current Controlled Trials IS RCT N78366977 PURPOSE To evaluate potential cost savings , trial data were used to determine the clinical outcomes for i.v . ertapenem given once daily and i.v . piperacillin-tazobactam given every six hours daily in treating diabetic foot infections . METHODS A cost-minimization analysis ( CMA ) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind r and omized trial who were treated solely as in patients and were clinical ly evaluable at fi nal assessment ( n = 99 ) . Cost per dose was calculated from ( a ) average hospital acquisition price per dose for ertapenem ( $ 40.52 ) or piperacillin-tazobactam ( $ 13.58 ) , ( b ) average U.S. wages and benefits for labor , based on nine published time- and -motion studies of i.v . antibiotic preparation and administration ( $ 3.10 ) , and ( c ) consumable supplies , using a 40 % discount off the manufacturer list price ( $ 2.90 ) . For each patient , the actual number of antibiotic doses given was multiplied by total cost per dose . RESULTS There were no significant differences between antibiotic groups with respect to patient demographics , percentage with a severe wound , and mean days of i.v . therapy . Compared with piperacillin-tazobactam , patients treated with ertapenem received significantly fewer mean doses ( 25.5 versus 7.5 ; p < 0.0001 ) and lower antibiotic-related costs ( $ 502.76 versus $ 355.55 , respectively ; p < 0.001 ) . The $ 147.21 difference between groups accounts for approximately 3 % of total hospital Medicare reimbursements for these infections . CONCLUSION A CMA of treatment of diabetic foot infections showed that , compared with piperacillin-tazobactam given four times daily i.v . , ertapenem given once daily i.v . was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v . therapy A cost-effectiveness analysis was performed following a double-blind , r and omized study of ampicillin/sulbactam ( A/S ) versus imipenem/cilastatin ( I/C ) for the treatment of limb-threatening foot infections in 90 diabetic patients . There were no significant differences between the treatments in terms of clinical success rate , adverse-event frequency , duration of study antibiotic treatment , or length of hospitalization . Costs of the study antibiotics , treatment of failures and adverse events , and hospitalization were calculated . Mean per-patient treatment cost in the A/S group was $ 14,084 , compared with $ 17,008 in the I/C group ( P = .05 ) , primarily because of lower drug and hospitalization costs and less-severe adverse events in the A/S group . Sensitivity analyses varying drug prices or hospital costs demonstrated that A/S was consistently more cost-effective than I/C. Varying the clinical success rate for each drug revealed that I/C would have to be 30 % more effective than A/S to change the economic decisions Abstract Objective : To calculate costs for the management of deep foot infections and to identify the most important factors related to treatment costs . Design : Costs for in-hospital care , surgery , investigations , antibacterials , visits to the foot-care team , orthopaedic appliances and topical treatment were calculated retrospectively from diagnosis until healing or death . Multiple regression analysis was used to identify factors that independently affect costs . Setting : A multidisciplinary foot-care team . Patients : 220 prospect ively followed patients with diabetes mellitus and deep foot infections who were referred to the team from 1986 to 1995 . Main Outcome Measures and Results : Total cost for healing without amputation was Swedish kronor (SEK)136 600 per patient , while the corresponding cost for healing with minor amputation was SEK260 000 and with major amputation was SEK234 500 . All costs were quoted in SEK at 1997 price levels ( £ 1 sterling and $ US1 equalled approximately SEK12.50 and SEK7.64 , respectively ) . The cost of antibacterials was 4%of total costs . The cost of topical treatment was 51 % of total costs and related to wound healing time . Number of weeks between diagnosis of deep foot infection and healing , and number of surgical procedures were variables that explained 95 % of costs in the multiple regression analysis . It was not possible to find any parameters present at diagnosis that could contribute to an explanation of total treatment costs . Conclusions : Topical treatment accounted for the largest proportion of total costs and the most important cost driving factors were wound healing duration and repeated surgery . Costs of antibacterials should not be used as an argument in the choice between early amputation and conservative treatment Infection plays a critical role in health care and impacts the cost of the treatment of diabetic foot ulcers ( DFU ) . To examine the cost reduction associated with the multidisciplinary treatment of infected DFU ( IDFU ) by obtaining early ( ie , within 48 hours of admission ) microbiological culture results , a descriptive , longitudinal study was conducted . Data were collected prospect ively from patient medical charts of a cohort of 67 patients ( mean age , 56.14 ± 12.3 years ; mean duration of diabetes , 14.95 ± 8 years ) with IDFU treated at a Mexican public health facility from January 1 to April 30 , 2010 . Information included demographic data ( age , gender , marital status , time elapsed since first diagnosis of diabetes mellitus type 2 [ DM2 ] ) , and the following clinical records : Wagner classification , bacterium type , antimicrobial resistance , length of hospital stay , and the antibiotic schedule utilized , as well as number and type of laboratory tests , medications , intravenous therapy , surgical and supportive treatment , type and number of specialists , and clinical outcome . Microcosting was used to calculate the unit cost of each medical treatment element . Using the Monte Carlo and Markov predictive simulation economical models , cost reduction associated with early identification of the specific microorganism through bacterial culture in IDFU was estimated . Based on the statistical results , differences between real and estimated costs when including early microbiological culture were identified and the number and type of most common species of infectious bacteria were detected . The total cost observed in the patient cohort was $ 502 438.04 USD , mean cost per patient was $ 7177.69 ± $ 5043.51 USD , and 72.75 % of the total cost was associated with the hospital stay length . The cost of the entire treatment including antibiotics was $ 359 196.16 USD ; based on the simulation of early microbiological culture , the model results showed cost could be reduced by 10 % to 25 % ( in this study , the cost could be as low as $ 304 624.63 USD ) . The use of early microbiological cultures on IDFU to determine the appropriate antibiotic can reduce treatment costs by > 30 % if hospital stay is part of the consideration Objective There is a paucity of research on patients presenting with uninfected diabetic foot ulcers ( DFU ) that go on to develop infection . We aim ed to investigate the incidence and risk factors for developing infection in a large regional cohort of patients presenting with uninfected DFUs . Methods We performed a secondary analysis of data collected from a vali date d prospect i ve state-wide clinical diabetic foot data base in Queensl and ( Australia ) . Patients presenting for their first visit with an uninfected DFU to a Diabetic Foot Service in one of thirteen Queensl and regions between January 2012 and December 2013 were included . Socio-demographic , medical history , foot disease history , DFU characteristics and treatment variables were captured at the first visit . Patients were followed until their DFU healed , or if their DFU did not heal for 12-months , to determine if they developed a foot infection in that period . Results Overall , 853 patients were included ; mean(st and ard deviation ) age 62.9(12.8 ) years , 68.0 % male , 90.9 % type 2 diabetes , 13.6 % indigenous Australians . Foot infection developed in 342 patients for an overall incidence of 40.1 % ; 32.4 % incidence in DFUs healed <3 months , 55.9 % in DFUs healed between 3–12 months ( p<0.05 ) . Independent risk factors ( Odds Ratio ( 95 % confidence interval ) ) for developing infection were : DFUs healed between 3–12 months ( 2.3 ( 1.6–3.3 ) ) , deep DFUs ( 2.2 ( 1.2–3.9 ) ) , peripheral neuropathy ( 1.8 ( 1.1–2.9 ) ) , previous DFU history ( 1.7 ( 1.2–2.4 ) ) , foot deformity ( 1.4 ( 1.0–2.0 ) ) , female gender ( 1.5 ( 1.1–2.1 ) ) and years of age ( 0.98 ( 0.97–0.99 ) ) ( all p<0.05 ) . Conclusions A considerable proportion of patients presenting with an uninfected DFU will develop an infection prior to healing . To prevent infection clinicians treating patients with uninfected DFUs should be particularly vigilant with those presenting with deep DFUs , previous DFU history , peripheral neuropathy , foot deformity , younger age , female gender and DFUs that have not healed by 3 months after presentation Diabetic foot ulcers with exposure of tendon , muscle , or bone imply a high probability for deep infections and amputations . Delayed healing times are often described . The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with st and ard treatment in diabetic feet with cavity ulcers . Patients with deep , exudative foot ulcers were included in a 12-week open , r and omised , comparative study . When ulcers stopped exudating , vaseline gauze was used in both groups until the end of the study . Costs were estimated for dressing material , staff and transportation . Clinical ly relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with st and ard treatment . The average weekly cost was SEK 903 and SEK 1,421 , respectively , of which the major part was costs for staff and transportation related to frequency of dressing changes . Treatment with cadexomer iodine ointment ( Iodosorb ) showed no clinical difference compared to topical treatment consisting of gentamicin solution , streptodornase/streptokinase , or dry saline gauze but was associated with considerably lower weekly treatment costs OBJECTIVES The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel ( Regranex ) plus good wound care ( GWC ) relative to treating them with GWC alone . METHODS A Markov simulation model was developed that includes six health states : Uninfected Ulcer , Infected Ulcer , Gangrene , Healed Ulcer , Healed Ulcer-History of Amputation , and Deceased . To predict clinical outcomes , information was taken from a specially design ed prospect i ve 9-month follow-up study of 183 neuropathic patients in the US treated with GWC . Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden . The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four r and omized clinical trials . A model application provides expected clinical outcomes for a cohort of patients . Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden . RESULTS Due to a higher rate of healing and a shorter average healing time , treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24 % relative to GWC alone . In addition , the corresponding number of amputations was 9 % lower for the becaplermin-treated cohort . The average expected cost of $ 12,078 US for an individual treated with GWC alone declines to $ 11,708 US for one treated with becaplermin , in spite of $ 1262 becaplermin costs . Expenses related to topical treatment and inpatient care account for 83 % of the re sources conserved . CONCLUSIONS Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer re sources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers . In light of the high and increasing incidence of such ulcers , the potential savings in costs and suffering may be important . Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practice s and price levels BACKGROUND Diabetic neuropathic foot ulcers are a risk factor for lower leg amputation . Many experts recommend offloading with fibreglass total contact casting , removable cast walkers , and irremovable cast walkers as a way to treat these ulcers . METHODS We completed a health technology assessment , which included an evaluation of clinical benefits and harms , value for money , and patient preferences for offloading devices . We performed a systematic literature search on August 17 , 2016 , to identify r and omized controlled trials that compared fibreglass total contact casting , removable cast walkers , and irremovable cast walkers with other treatments ( offloading or non-offloading ) in patients with diabetic neuropathic foot ulcers . We developed a decision-analytic model to assess the cost-effectiveness of fibreglass total contact casting , removable cast walkers , and irremovable cast walkers , and we conducted a 5-year budget impact analysis . Finally , we interviewed people with diabetes who had lived experience with foot ulcers , asking them about the different offloading devices and the factors that influenced their treatment choices . RESULTS We identified 13 r and omized controlled trials . The evidence suggests that total contact casting , removable cast walkers , and irremovable cast walkers are beneficial in the treatment of neuropathic , noninfected foot ulcers in patients with diabetes but without severe peripheral arterial disease . Compared to removable cast walkers , ulcer healing was improved with total contact casting ( moderate quality evidence ; risk difference 0.17 [ 95 % confidence interval 0.00 - 0.33 ] ) and irremovable cast walkers ( low quality evidence ; risk difference 0.21 [ 95 % confidence interval 0.01 - 0.40 ] ) . We found no difference in ulcer healing between total contact casting and irremovable cast walkers ( low quality evidence ; risk difference 0.02 [ 95 % confidence interval -0.11 - 0.14 ] ) . The economic analysis showed that total contact casting and irremovable cast walkers were less expensive and led to more health outcome gains ( e.g. , ulcers healed and quality -adjusted life-years ) than removable cast walkers . Irremovable cast walkers were as effective as total contact casting and were associated with lower costs . The 5-year budget impact of funding total contact casting , removable cast walkers , and irremovable cast walkers ( device costs only at 100 % access ) would be $ 17 to $ 20 million per year . The patients we interviewed felt that wound healing was improved with total contact casting than with removable cast walkers , but that removable cast walkers were more convenient and came with a lower cost burden . They reported no experience or familiarity with irremovable cast walkers . CONCLUSIONS Ulcer healing improved with total contact casting , irremovable cast walkers , and removable cast walkers , but total contact casting and irremovable cast walkers had higher rates of ulcer healing than removable cast walkers . Increased access to offloading devices could result in cost savings for the health system because of fewer amputations . Patients with diabetic foot ulcers reported a preference for total contact casting over removable cast walkers , largely because they perceived wound healing to be improved with total contact casting . However , cost , comfort , and convenience are concerns for patients OBJECTIVE Diabetes is one of the most widespread diseases in Germany . Common complications are diabetic foot ulcers ( DFU ) , which are associated with a cost-intensive treatment and serious adverse events , such as infections , amputations . This cost-effectiveness analysis compares two treatment options for patients with DFU : a TLC-NOSF dressing versus a neutral dressing , assessed through a European double-blind r and omised controlled trial ( RCT ) , Explorer . METHODS The evaluation of the clinical outcomes was associated to direct costs ( costs for dressings , nursing time , hospitalisation etc . ) of both dressings , from the perspective of the statutory health insurance in Germany . Due to the long mean healing time of a DFU , the observation period was extended from 20 to 100 weeks in a Markov model . RESULTS After 20 weeks , and with complete closure as a primary endpoint , the model revealed direct treatment costs for DFU of € 2,864.21 when treated with a TLC-NOSF dressing compared with € 2,958.69 with the neutral control dressing ( cost-effectiveness : € 6,017.25 versus € 9,928.49 ) . In the Markov model ( 100 weeks ) the costs for the TLC-NOSF dressing were € 5,882.87 compared with € 8,449.39 with the neutral dressing ( cost-effectiveness : € 6,277.58 versus € 10,375.56 ) . The robustness of results was underlined by several sensitivity analyses for varying assumptions . The frequency of weekly dressing changes had the most significant influence in terms of parameter uncertainty . CONCLUSION Overall , the treatment of DFU with a TLC-NOSF dressing is supported from a health economic perspective , because both the treatment costs and the cost-effectiveness were superior compared with the neutral wound dressing |
11,170 | 21,824,384 | In meta- analysis , CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range .
Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing , specifically insulin and vitamin K antagonist dosing .
However , studies were small and generally of modest quality , and effects on patient outcomes were uncertain , with no convincing benefit in the largest studies . | Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety .
Computerized clinical decision support systems ( CCDSSs ) may improve the net benefit of these drugs .
The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing . | Background — Oral anticoagulation ( OAC ) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range . This report examines how differences in time in therapeutic range ( TTR ) between centers and between countries affect the outcomes of OAC therapy . Methods and Results — In a posthoc analysis , the TTRs of patients on OAC in a r and omized trial of OAC versus clopidogrel plus aspirin ( Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ ACTIVE W ] ) were used to calculate the mean TTR for each of 526 centers and 15 countries . Proportional-hazards analysis , with and without adjustment for baseline variables , was performed , with patients stratified by TTR quartile and country . A wide variation in TTRs was found between centers , with mean TTRs for centers in the 4 quartiles of 44 % , 60 % , 69 % , and 78 % . For patients at centers below the median TTR ( 65 % ) , no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC ( relative risk , 0.93 ; 95 % confidence interval , 0.70 to 1.24 ; P=0.61 ) . However , for patients at centers with a TTR above the study median , OAC had a marked benefit , reducing vascular events by > 2-fold ( relative risk , 2.14 ; 95 % confidence interval , 1.61 to 2.85 ; P<0.0001 ) . Mean TTR also varied between countries from 46 % to 78 % ; relative risk ( clopidogrel plus aspirin versus OAC ) varied from 0.6 to 3.6 ( a 5-fold difference ) . A population -average model predicted that a TTR of 58 % would be needed to be confident that patients would benefit from being on OAC . Conclusions — A wide variation exists in international normalized ratio control , as measured by TTR , between clinical centers and between countries , which has a major impact on the treatment benefit of OAC therapy . For centers and countries , a target threshold TTR exists ( estimated between 58 % and 65 % ) below which there appears to be little benefit of OAC over antiplatelet therapy Three dosage-prediction methods for initial in-hospital stabilization of warfarin therapy were evaluated . Adult in patients who had received warfarin sodium 10 mg daily for less than three days were eligible for the study . After receiving their third warfarin dose , patients were r and omly assigned to have their warfarin dosages adjusted using one of three dosage-prediction methods : by analog computer ( n = 31 ) , linear regression ( n = 22 ) , or empiric dosing by the physician ( n = 34 ) . A prothrombin time ( PT ) ratio ( patient PT divided by control PT ) between 1.3 and 2.5 was considered to be in the therapeutic range . For patients who achieved a stable PT ratio ( defined as a PT ratio between 1.3 and 2.5 that varied by less than 0.05 on two consecutive days or by less than 0.1 on three consecutive days without a dosage change ) before discharge , the number of days ( time to stabilization ) from administration of the first warfarin dose to achievement of the warfarin dosage that produced a stable PT ratio ( stabilization dosage ) was compared . A total of 54 patients met the study criteria for a stable PT ratio before hospital discharge ( analog computer , n = 20 ; linear regression , n = 15 ; empiric dosing , n = 19 ) . The mean times to stabilization were 6.8 days in the analog-computer group , 7.3 days in the linear-regression group , and 8.4 days in the empiric-dosing group ; these times were not significantly different . All 20 stabilized patients in the analog-computer group achieved a stable PT ratio by the fourth dosage prediction . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND There is increased pressure on primary care physicians to monitor oral anticoagulation . OBJECTIVE To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic , involving near-patient testing and computerized decision support software , compared with routine hospital management based on a variety of clinical outcome measures . METHODS A r and omized , controlled trial in 12 primary care practice s in Birmingham , Engl and ( 9 intervention and 3 control ) . Two control population s were used : patients individually r and omly allocated as controls in the intervention practice s ( intra practice controls ) and all patients in control practice s ( inter practice controls ) . Intervention practice s ' patients were r and omized to the intervention ( practice -based anticoagulation clinic ) or control ( hospital clinic ) group . The main outcome measure was therapeutic control of the international normalized ratio . RESULTS Three hundred sixty-seven patients were recruited ( 122 intervention patients , 102 intra practice control patients , and 143 inter practice control patients ) . St and ard measures of control of the international normalized ratio ( point prevalence ) showed no significant difference between the intervention and control groups . Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group ( paired t test , P = .008 ) . CONCLUSIONS Nurse-led anticoagulation clinics can be implemented in novice primary care setting s by means of computerized decision support software and near-patient testing . Care given by this model is at least as good as routine hospital follow-up . The model is generalizable to primary health care centers operating in developed health care systems AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme This study was undertaken to determine if a computerized pharmacokinetic program for adjusting theophylline infusion rates could attain a goal serum theophylline level more accurately than physician‐derived adjustments and what clinical impact this would have . Thirty‐five patients with diagnoses of asthma or chronic obstructive pulmonary disease were r and omized to a control group ( empiric ) or experimental group ( kinetic ) after initial theophylline levels were drawn from each group . After second levels were drawn , patients in the kinetic group had their infusion rates adjusted by the computerized pharmacokinetic program to achieve a level of 15 mg/L , whereas patients in the empiric group had their infusions adjusted empirically by the primary care physicians to achieve a serum theophylline level of 15 mg/L. A final theophylline level was obtained just before the infusion was discontinued . The kinetic group was closer to the goal level of 15 mg/L than the empiric group , but this was not statistically significant ( 14.8 ± 4.4 versus 12.6 ± 4.1 ; p > 0.05 ) . The total number of days that patients were receiving intravenous theophylline was slightly longer for the kinetic group ( 4.1 ± 3.3 versus 3.2 ± 1.5 ; p > 0.05 ) as was the total number of hospital days , but neither of these were statistically significant ( 11.4 ± 21.6 versus 8.8 ± 15.4 days ; p > 0.05 ) . There were no differences between the two groups in the number of subtherapeutic or toxic levels , and there were no significant differences in arterial blood gas measurements . We were unable to show in this study any clinical advantage to adjusting the dosage of a theophylline infusion by a computerized pharmacokinetic program compared with adjustments made empirically by a physician AIMS --To compare the effectiveness of three computerised systems that are currently used for assisting warfarin control in out patients with the customary dosing method used by experienced medical staff . METHODS --A pilot r and omised study of three systems with a follow up independently r and omised study of two of these was made on 186 patients receiving long term treatment or who had recently started warfarin treatment and had been discharged from hospital . RESULTS --All three computerised systems seemed to give satisfactory control compared with the traditional dosing method . For patients receiving more intensive treatment with an assigned target range of 3.0 - 4.5 computerised dosage programs achieved significantly better control ; the medical staff undertreated such patients almost 50 % of the time . CONCLUSION --Computer based programs can assist outpatient anticoagulant control with warfarin during both early and long term treatment . For most patients the control achieved is as good as that obtained by the customary method of dosing , by experienced clinic doctors , although the latter tend to be too conservative when dosing patients within the intense target range of 3.0 to 4.5 International Normalised Ratio ( INR ) . The computers were significantly more successful in this higher range Abstract In 42 patients requiring digitalis , and r and omly divided into two groups , the performance of a computer program using patient size and renal function to compute digoxin dosage was compared to that of unaided physician judgment . Serum digoxin concentrations were measured repeatedly . Efficacy was measured by changes in the manifestations of heart failure , and toxicity by electrocardiographic criteria . For each patient , physicians specified a desired serum digoxin concentration and predicted this concentration at each visit . For one group , the computer program suggested the dosage needed to achieve the desired digoxin concentration . Efficacy was the same in both groups , and there was no toxicity . Although the computer slightly outperformed the physicians , prediction and achievement errors were unacceptably large . Hence , much between-patient variability in serum digoxin concentrations remains unexplained after adjustments for dose , body size and renal function . This argues for measurement of digoxin With increasing work-loads in anticoagulant clinics different methods of service delivery need evaluation . The quality of anticoagulant control achieved by a nurse-practitioner using a computer decision-support system ( CDSS ) was compared with that achieved by trainee doctors without CDSS . Eighty-one out- patients ( group A , therapeutic range 2 - 3 ) and 96 out- patients ( group B , therapeutic range 3 - 4.5 ) were r and omized to management by a nurse-practitioner or by trainee doctors ( clinicians ) . Thirty-seven patients in group A and 50 patients in group B were r and omized to be managed by the nurse-practitioner . In group A , patients in the nurse-practitioner group spent a longer time in the therapeutic range than those in the clinician group ( 60.7 % compared with 51.6 % ) . Dose suggestion acceptance in the nurse-practitioner group ( 88 % ) was higher compared with agreement between the CDSS and the clinicians ( 60 % ) . In group B , patients in the clinician group spent a slightly longer time in the therapeutic range ( 70 % compared with 67.6 % ) . Acceptance of dose suggestion was lower in the nurse-practitioner group ( 67 % ) compared with agreement between the CDSS and the clinicians ( 73 % ) . In conclusion , the CDSS can improve the quality of control of warfarin therapy by a nurse-practitioner over that by trainee doctors for the therapeutic range 2 - 3 . Similar quality of control is achieved for the therapeutic range 3 - 4.5 . The CDSS may be used by nurse-practitioners to achieve safe and effective anticoagulation in hospital-based or out-reach anticoagulant clinics OBJECTIVES A clinical trial , " Belgian Improvement Study on Oral Anticoagulation Therapy ( BISOAT ) , " significantly improved the quality after implementing four different quality -improving interventions in four r and omly divided groups of general practitioners ( GPs ) . The quality -improving interventions consisted of multifaceted education with or without feedback reports on their performance , international normalized ratio ( INR ) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy . The quality improvement in INR control versus baseline was similar in the four groups . The aim of the current study was to calculate the cost-effectiveness and influencing factors of the four quality -improving interventions compared with usual care . METHODS Activity-based costing techniques with question naires were used to determine the global costs per patient per month in the different intervention groups . Effectiveness data were obtained from the BISOAT study . Cost-effectiveness was expressed as cost per additional day within a 0.5 range from INR target . RESULTS The one-time cost of multifaceted education was 49,997 euro for the whole study . Monthly continuous costs per intervention ranged between 37 euro and 54 euro per patient . Using the CoaguChek in combination with the multifaceted education was associated with net savings and quality improvement , hence dominated usual care . Sensitivity analyses showed improved cost-effectiveness with extended duration and with increased program size . CONCLUSION Implementation of the combination multifaceted education with the use of the CoaguChek is a cost-effective new organizational model of oral anticoagulation management in general practice BACKGROUND Increased dem and for oral anticoagulants is overwhelming facilities worldwide , result ing in increasing use of computer assistance . A multicenter clinical endpoint study has been performed to compare the safety and effectiveness of computer-assisted dosage with dosage by experienced medical staff at the same centers . METHODS A r and omized study of dosage of two commercial computer-assisted dosage programs ( PARMA 5 and DAWN AC ) vs. manual dosage at 32 centers with an established interest in oral anticoagulation in 13 countries . The aim was to recruit a minimum of 16,000 patient-years r and omized to medical staff or computer-assisted dosage . In total , 13,219 patients participated , 6503 patients being r and omized to medical staff and 6716 to computer-assisted dosage . The safety and effectiveness of computer-assisted dosage were compared with those of medical staff dosage . RESULTS In total , 13,052 patients were recruited ( 18,617 patient-years ) . International Normalized Ratio ( INR ) tests numbered 193 890 with manual dosage and 193,424 with computer-assisted dosage . The number of clinical events with computer-assisted dosage was lower ( P = 0.1 ) , but in the 3209 patients with deep vein thrombosis/pulmonary embolism , they were reduced by 37 ( 24 % , P = 0.001 ) . Time in target INR range was significantly improved by computer assistance as compared with medical staff dosage at the majority of centers ( P < 0.001 ) . CONCLUSIONS The safety and effectiveness of computer-assisted dosage has been demonstrated using two different marketed programs in comparison with experienced medical staff dosage at the centers with established interest in anticoagulation . Significant prevention of clinical events in patients with deep vein thrombosis/pulmonary embolism and the achievement of target INR in all clinical groups has been observed . The reliability and safety of other marketed computer-assisted dosage programs need to be established OBJECTIVE To measure the impact of a computerized guideline for glucose regulation in an ICU . DESIGN A r and omized , controlled trial with an off-on-off design . METHODS We implemented a glucose regulation guideline in an intensive care unit in paper form during the first study period . During the second period , the guideline was r and omly applied in either paper or computerized form . In the third period , the guideline was available only in paper form . MEASUREMENTS AND RESULTS We analyzed data for 484 patients . During the intervention period , the control group included 54 patients and the computerized intervention group included 66 patients . The two guideline -related outcome measures consisted of compliance with : ( a ) glucose measurement timing recommendations and ( b ) insulin dose advice . We measured clinical impact as the proportion of time that glucose levels fell within target range . In the first ( paper-based ) study period , 29.0 % of sample s occurred with optimal timing ; during the second period , this increased to 35.5 % for paper-based and to 40.2 % for computerized protocol s. The third study period timeliness scores reverted to the first period rates . Late ( suboptimal ) sampling occurred for 66 % of glucose measurements in the first study period , for 42 % of paper-based and 28 % of computer-based protocol sample s in the second period , and for 50.0 % of sample s in the third study period . In the first study period , insulin-dosing guideline compliance was 56.3 % ; in the second period , it was 64.2 % for paper-based and 77.3 % for computer-based protocol s , and it fell to 42.4 % in the third period . For the second study period , the time that a patient 's glucose values fell within target range improved for both the control ( 52.9 % ) and the computerized groups ( 54.2 % ) compared with the first study period ( 44.3 % ) and the third period ( 42.3 % ) . CONCLUSION Implementing a computerized version of a guideline significantly improved timeliness of measurements and glucose level regulation for critically ill patients compared with implementing a paper-based version of the guideline OBJECTIVE Errors of omission are a common cause of systems failures . Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments . The authors hypothesized that automated , guideline -based reminders to physicians , provided as they wrote orders , could reduce these omissions . DESIGN The study was performed on the inpatient general medicine ward of a public teaching hospital . Faculty and housestaff from the Indiana University School of Medicine , who used computer workstations to write orders , were r and omized to intervention and control groups . As intervention physicians wrote orders for 1 of 87 selected tests or treatments , the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders . The physicians could accept or reject these suggestions . RESULTS During the 6-month trial , reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians . Intervention physicians ordered the suggested corollary orders in 46.3 % of instances when they received a reminder , compared with 21.9 % compliance by control physicians ( p < 0.0001 ) . Physicians discriminated in their acceptance of suggested orders , readily accepting some while rejecting others . There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups . CONCLUSION This study demonstrates that physician workstations , linked to a comprehensive electronic medical record , can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake OBJECTIVE Recommendations for routine laboratory monitoring to reduce the risk of adverse medication events are not consistently followed . We evaluated the impact of electronic reminders delivered to primary care physicians on rates of appropriate routine medication laboratory monitoring . DESIGN We enrolled 303 primary care physicians caring for 1,922 patients across 20 ambulatory clinics that had at least one overdue routine laboratory test for a given medication between January and June 2004 . Clinics were r and omized so that physicians received either usual care or electronic reminders at the time of office visits focused on potassium , creatinine , liver function , thyroid function , and therapeutic drug levels . MEASUREMENTS Primary outcomes were the receipt of recommended laboratory monitoring within 14 days following an outpatient clinic visit . The effect of the intervention was assessed for each reminder after adjusting for clustering within clinics , as well as patient and provider characteristics . RESULTS Medication-laboratory monitoring non-compliance ranged from 1.6 % ( potassium monitoring with potassium-supplement use ) to 6.3 % ( liver function monitoring with HMG CoA Reductase Inhibitor use ) . Rates of appropriate laboratory monitoring following an outpatient visit ranged from 14 % ( therapeutic drug levels ) to 64 % ( potassium monitoring with potassium-sparing diuretic use ) . Reminders for appropriate laboratory monitoring had no impact on rates of receiving appropriate testing for creatinine , potassium , liver function , renal function , or therapeutic drug level monitoring . CONCLUSION We identified high rates of appropriate laboratory monitoring , and electronic reminders did not significantly improve these monitoring rates . Future studies should focus on setting s with lower baseline adherence rates and alternate drug-laboratory combinations BACKGROUND Increasing indications for oral anticoagulation has led to pressure on general practice s to undertake therapeutic monitoring . Computerized decision support ( DSS ) has been shown to be effective in hospitals for improving clinical management . Its usefulness in primary care has previously not been investigated . AIM To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled , defined as within the appropriate therapeutic range of International Normalised Ratio ( INR ) . METHOD All patients receiving warfarin from two Birmingham inner city general practice s were invited to attend a practice -based anticoagulation clinic . In practice A all patients were managed using DSS . In practice B patients were r and omized to receive dosing advice either through DSS or through the local hospital laboratory . Clinical outcomes , adverse events and patient acceptability were recorded . RESULTS Forty-nine patients were seen in total . There were significant improvements in INR control from 23 % to 86 % ( P > 0.001 ) in the practice where all patients received dosing through DSS . In the practice where patients were r and omized to either DSS or hospital dosing , logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients ( P < 0.001 ) . Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months ( 24 days to 36 days ) ( P = 0.033 ) . Adverse events were comparable between hospital and practice -dosed patients , although a number of esoteric events occurred . Patient satisfaction with the practice clinics was high . CONCLUSION Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control , frequency of review and general acceptability A computer was used to prospect ively detect and suggest responses to simple , medication-related events as reflected in a computerized record in a prospect i ve , r and omized study of a diabetes clinic with primary -care responsibility . There were two categories of event/suggestions : when the last observation of a test required for medication control was too old , the computer suggested a repeat ; and when an abnormality with therapeutic implication s was detected , the computer suggested a specific change in therapeutics . Clinicians responded to 36 % of events in the first category with computer reminders and 11 % without ( P less than 0.0001 ) ; they responded to 28 % of events in the second category with computer assistance and 13 % without ( P less than 0.026 ) . For the most clinical ly significant of these second category events , the difference was even greater : 47 % with and 4 % without computer assistance ( P less than 0.0004 ) . I believe that computer detection and response ( in the form of reminders ) to simple clinical events will change clinician behavior OBJECTIVE The aim of this study was to compare a st and ard insulin protocol with a computer-guided glucose management system to determine which method achieves tighter glucose control . DESIGN A prospect i ve , r and omized trial . SETTING A cardiothoracic intensive care unit ( ICU ) in a large academic medical center . PARTICIPANTS Forty patients with diabetes mellitus who were scheduled for cardiac surgery . INTERVENTIONS After induction of anesthesia and for the first 9 hours in the ICU , each subject received a st and ardized infusion of a 10 % glucose solution at a rate of 1.0 mL/kg/h ( ideal body weight ) . The subjects were then r and omized to have their glucose controlled by either a paper-based insulin protocol or by a computer-guided glucose management system ( CG ) . The desired range for blood glucose was set between 90 and 150 mg/dL. MEASUREMENTS AND MAIN RESULTS There were no differences between groups in baseline characteristics . Patients in the CG group spent more time in the desired range during both the intraoperative phase ( 49 % v 27 % , p = 0.001 ) and the ICU phase ( 84 % v 60 % , p < 0.0001 ) . There were no statistical differences between groups in the number of hypoglycemia episodes . CONCLUSIONS The computer-guided glucose management system achieved tighter blood glucose control than a st and ard paper-based protocol in diabetic patients undergoing cardiac surgery . However , the low proportion of blood glucose recordings within the desired range in both groups during the intraoperative period reflects the challenges associated with achieving normoglycemia during cardiac surgery A computerized medical decision-making system was used to monitor signs and predisposing factors of digoxin intoxication in patients receiving digoxin . This process automatically review ed the patient 's data base nightly for drug interactions , laboratory data and electrocardiographic findings with known association with digoxin intoxication . These decisions were formated into a " digoxin alert report " and sent to line printers in the nursing division to be placed on the individual patients ' charts . To assess the effect of these reports on patient management , a r and omized double-blind study was undertaken . Patients were assigned to an alert or nonalert group . Alert reports were withheld from charts of patients in the nonalert group . A medical record review was subsequently carried out , wherein the physician 's orders were search ed to identify actions taken with possible relation to the digoxin alerts . The computer monitored 396 patients over a 3 month period . Of these , 211 ( 53 % ) were r and omized to the alert group and 185 ( 47 % ) to the nonalert group . Seventy-two percent of patients received at least one alert . The most frequently occurring alerts included : hypoxemia , hypokalemia , concurrent use of a beta-adrenergic blocking agent , renal insufficiency and ventricular arrhythmia . Results from the record review demonstrated a 22 % increase in physician actions for the alert group . Specifically , patients in the alert group were 2.7 times more likely to have a serum digoxin determination ordered and 2.8 times more likely to have digoxin withheld on the day of a digoxin alert than were patients in the nonalert group Mitra R , Marciello MA , Brain C , Ahangar B , Burke DT : Efficacy of computer-aided dosing of warfarin among patients in a rehabilitation hospital . Am J Phys Med Rehabil 2005;84:423–427 . Objective : To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal . Design : R and omized , double-blinded , clinical trial in an inpatient rehabilitation hospital . A total of 30 consecutive patients admitted receiving warfarin were r and omized to either clinician dosing or computer-aided warfarin dosing for the duration of their hospitalization . The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws . Exclusion criteria included short length of stay ( n = 110 , 39 % ) and a physician declared international normalized ratio target range of < 2.0 ( n = 67 , 23 % ) . A total of 73 patients were excluded because of heme-positive stools at admission , recent gastrointestinal bleed , early discharge or consent refusal . Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0–3.0 for the computer-dosed group ( n = 14 ) . Several physicians recommended warfarin dosages for the second group ( n = 16 ) . Two were dropped from the computer model secondary to lost data files for these two patients . Results : Computer-aided dosing of warfarin result ed in 61.7 % of days within the therapeutic range ( international normalized ratio , 2–3 ) , whereas clinician dosing result ed in only 44.1 % . There were no significant differences in the number of blood draws or demographic variables between the two groups . Conclusion : Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians . There were no significant differences in the number of recommended blood draws A prospect i ve r and omised trial was conducted in critically ill patients to evaluate a computer aided pharmacokinetic method of aminoglycoside dose prediction based on 3 measured plasma concentrations following the loading dose . The ability of this method to achieve therapeutic plasma aminoglycoside concentrations early in the course of treatment was compared with that of a nomogram approach based on creatinine clearance estimated using the formula of Cock-roft and Gault . Ninety-two percent of patients in the computer group achieved peak plasma concentrations within the optimum range of 6–10 mg/l at 48–72 h compared with 21 % of control group patients ( p=0.0009 ) . The mean peak plasma concentration of 7.45 mg/l at 48–72 h in the computer group was closer to the target concentration of 8 mg/l than was the 5.14 mg/l in the control group ( p=0.0004 ) . There was no significant difference between the groups in measured indices of renal function , both groups showing an improvement in mean estimated creatinine clearance from the beginning to the end of the course of treatment . Dosing based on individualised pharmacokinetic data is therefore a more reliable method of achieving therapeutic blood concentrations early in the course of treatment than is nomogram based dosing . Other studies suggest that this should be associated with a reduction in mortality in severe infections BACKGROUND AND OBJECTIVES We carried out a prospect i ve , r and omized trial to test whether a computer-based decision support system to initiate and maintain oral anticoagulant ( OA ) treatment can improve the laboratory quality of therapy . DESIGN AND METHODS Two separate sets of patients on oral anticoagulants , in five Italian anticoagulant clinics , were studied : 335 patients in the first three months of treatment ( stabilization phase ) , 916 patients ( 775 patient-years ) beyond the third month of treatment ( maintenance phase ) . Patients were r and omized to a computerized system , which included algorithms able to suggest OA dosing and to schedule appointments ( computer-aided dosing ) or to an arm in which OA were prescribed by the same teams of expert physicians without such algorithms ( control group ) . Primary outcomes were : A ) the percentage of patients reaching a stable state of anticoagulation during each of the first three months of treatment ; B ) the percentage of time individuals spent within the aim ed therapeutic range ( maintenance phase ) . RESULTS Patients in the computer-aided dosing group achieved a stable state significantly faster ( p<0.01 ) and they spent more time within the therapeutic range during maintenance ( p<0.001 ) than controls . The favorable effect of computer-aided dosing was mainly due to a reduction of the time spent below the therapeutic range and was associated with an increase of mean INR value , of anticoagulant drug dosage , and with a reduction of the number of appointments per patient ( all changes significant : p<0.001 ) . INTERPRETATION AND CONCLUSIONS The computer decision-aided support improves the laboratory quality of anticoagulant treatment , both during long-term maintenance and in the early , highly unstable phase of treatment , and it also significantly reduces the number of scheduled laboratory controls In a prospect i ve , r and omized study at two university hospitals , the authors examined how effectively housestaff physicians ( n = 36 ) managed the initiation of warfarin therapy compared with a computer-assisted dosing regimen ( n = 39 ) using the software program Warfcalc , which was managed by one of the authors . Target prothrombin time ratios were selected by the physicians . Study endpoints included : the time to reach a therapeutic prothrombin ratio , the time to reach a stable therapeutic dose , the number of patients transiently overanticoagulated , the number of bleeding complications , and the accuracy of the predicted maintenance dose , which was assessed at steady-state 10 - 14 days later . Computer-assisted dosing consistently out-performed the physicians : a stable therapeutic dose was achieved 3.7 days earlier ( p = 0.002 ) , fewer patients were overanticoagulated ( 10 % versus 41 % ) , and the predicted maintenance dose was in the therapeutic range in 85 % of the computer-dosed patients versus 42 % of the physician group ( p less than 0.002 ) . For physicians who did not routinely manage warfarin therapy , computer-assisted dosing improved the accuracy of dosing and shortened the time required to achieve a stable therapeutic dose Objective : To evaluate a computerized scheduling model that employs nonlinear optimization to recommend optimal follow-up intervals for patients taking warfarin . Design : R and omized trial . Setting : 5 anticoagulation clinics . Patients / participants : 620 patients expected to receive warfarin for ≥6 weeks . Interventions : Computer-generated recommendations for scheduling the next visit were presented to or withheld from practitioners . Measurements and main results : The main outcome measures were the follow-up interval scheduled by the provider , the interval at which the patient actually returned to clinic , and the quality of anticoagulation control ( computed as the absolute difference between the measured and target prothrombin times [ PTRs ] or international normalized ratios [ INRs ] ) . Follow-up intervals scheduled for the patients whose practitioners received computer-generated recommendations were significantly longer than those for control patients ( mean , 4.4 vs 3.5 weeks , p<0.001 ) , despite the fact that the practitioners modified the suggested return interval by > 1 week on 40 % of the visits . The interval at which the intervention group actually returned to clinic was also longer ( mean , 4.4 vs 4.1 weeks , p<0.05 ) , even though the control patients tended to return at longer intervals than were scheduled by their practitioners . Control of anticoagulation was nearly the same among experimental and control patients . Life-threatening complications occurred in the care of three experimental patients and one control patient , while other serious complications occurred in the care of 16 experimental patients and 17 control patients . Conclusions : Recommendations based on nonlinear optimization prompted clinicians to schedule less frequent follow-up for patients taking warfarin , with no deterioration in anticoagulation control . This approach to scheduling can potentially reduce utilization while maintaining quality of care for patients who require long-term monitoring We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections . Patients were r and omized to a control ( dosing based on physician choice ; n = 75 ) or experimental group ( dosing based on the bayesian program ; n = 72 ) . Both groups used serum aminoglycoside concentration data when making dosing decisions . Improved response rates were seen in the experimental ( 60 % ; 42/68 ) compared with the control group ( 48 % ; 36/68 ) . A higher , but not statistically significant , incidence of toxicity was found in the control ( 7/75 ; 9.7 % ) versus the experimental group ( 4/72 ; 5.1 % ) . Mean length of total hospital stay was significantly longer for patients in the control group ( 20.3 days ) compared with the experimental group ( 16.0 days ) ( p = 0.028 ) . The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy . On the basis of a reduced length of stay , a potential cost savings of $ 1311 per patient can be achieved Failure to adequately anticoagulate the blood of patients receiving recombinant tissue plasminogen activator ( TPA ) leads to greater rates of rethrombosis . In a multicentered , r and omized trial in 51 patients we compared the ability to achieve and maintain therapeutic anticoagulation by use of computer‐assisted heparin therapy or the GUSTO ( Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries ) heparin nomogram guidelines in patients with myocardial infa rct ion treated with recombinant TPA . Heparin therapy was initiated with either computer‐generated starting doses or GUSTO guideline starting doses . Activated partial thromboplastin times were measured every 6 to 8 hours for the first 24 hours . The therapeutic range used in this trial was 1.5 to 2.5 times the patient 's baseline activated partial thromboplastin time ( APTT ) . Ninety‐four percent of the APTT ratios in the computer group were equal to or greater than 1.5 in the first 24 hours compared with 78 % in the GUSTO group ( p < 0.009 ) . No significant difference in bleeding was found ( 7.7 % for GUSTO ; 4.2 % for computer ) . Incremental time‐dependent changes in heparin dose were found ( day 1 , 1110 ± 243 units/hr , APTT ratio = 2.5 ± 1.4 ; day 3 , 1380 ± 374 units/hr , APTT ratio , 1.9 ± 0.4 ) . Computer‐assisted heparin therapy TPA results in superior anticoagulation accuracy compared with the GUSTO guidelines . In addition , the pharmacodynamic response to heparin changes in the 2 to 3 days after administration of TPA , leading to greater heparin requirements A r and omized prospect i ve study compared achievement and maintenance of therapeutic plasma concentrations in patients receiving computer-assisted ( CA ) initial lidocaine hydrochloride therapy , design ed pharmacokinetically to achieve and maintain a chosen plasma concentration , v conventional lidocaine therapy ( CT ) . A separate audit of outcome was also conducted . The CA regimens provided more effective concentrations in the first hour than did CT , 2.65 v 1.5 micrograms/mL average . In the audit , ventricular fibrillation occurred in two of 78 CA v eight of 78 CT patients . Dosage adjustments were required in two CA patients v 33 CT patients . The CA therapy improved therapeutic precision , reduced dosage adjustments , and may have improved safety during initial lidocaine therapy before fitting to plasma concentration data for subsequent feedback . An improved clinical computer program now also fits to plasma concentration data . It is accessed and used routinely by hospitals over an international time-sharing network Summary The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed , comparing the results achieved by computer-assisted dosing , design ed to achieve and maintain a serum theophylline level of 16 μg · ml−1 ( 10 patients ) with those of unaided physicians ( 15 control patients ) . The outcome measures compared were clinical improvement , peak expiratory flow rate and serum theophylline concentration . Loading doses of theophylline in the control and computer groups were : 167 and 437 mg , respectively . Initial serum theophylline concentrations , measured 20 min after the loading dose , were 13.6 and 17.0 μg · ml−1 in the control and computer groups , respectively . In patients who had not received theophylline prior to admission , loading doses and initial concentrations were : 200 mg and 9.4 μg · ml−1 in the control group ( n = 5 ) versus 613 mg and 15.7 μg · ml−1 in the computer group ( n = 4 ) , respectively . During maintenance therapy , serum theophylline concentrations were kept in the therapeutic range ( 10–20 μg · ml−1 ) throughout 51 % and 77 % of the hospitalisation period , in the control and computer groups , respectively . There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate . The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm . There was no correlation between clinical outcome and serum theophylline concentration , but this may have been due to the small sample size and modest difference in serum theophylline between the two groups . The findings serve as an additional argument in favour of the trend away from reliance on theophylline as first line therapy in acute bronchospasm Abstract Objectives : To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors . Design : R and omised controlled trial . Setting : District general hospital in North London . Subjects : 148 in patients requiring start of warfarin treatment . Interventions : Management by trainee doctors ( to achieve therapeutic range of international normalised ratio of 2 to 3 ) with indirect assistance from computerised decision support system ( intervention group ) or without such assistance ( control group ) . Main outcome measures : Median time to therapeutic range , stable dose , and first pseudoevent ( excessive international normalised ratio after therapeutic range has been reached ) and person time spent in the therapeutic range . Results : 72 patients were r and omised to the intervention group and 76 to control group . Median time to reach international normalised ratio of ≥2 was not significantly different in the two groups ( 3 days ) . Median time to achieve a stable dose was significantly lower in intervention group than in controls ( 7 days v 9 days , P=0.01 ) without excessive overtreatment or undertreatment with anticoagulant . Patients in intervention group spent greater proportion of time in therapeutic range , both as in patients ( 59 % v 52 % ) and out patients ( 64 % v 51 % ) . Conclusion : The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors . Key messages The quality of control of warfarin doses during initiation and maintenance of oral anticoagulation is generally poor We investigated whether a computerised decision support system for initiation and control of oral anticoagulation improved quality of anticoagulant control achieved by trainee doctors The median time to achieve a stable dose was significantly lower in the group assisted by the decision support system than in controls , without excessive overtreatment or undertreatment with anticoagulant Patients in the group with the decision aid spent more time within the therapeutic range both as in patients and out patients The computerised decision support system was safe and effective and improved quality of initiation and control of warfarin treatment by trainee PURPOSE The objective of this study is to evaluate blood glucose ( BG ) control efficacy and safety of 3 insulin protocol s in medical intensive care unit ( MICU ) patients . METHODS This was a multicenter r and omized controlled trial involving 167 MICU patients with at least one BG measurement > or=150 mg/dL and one or more of the following : mechanical ventilation , systemic inflammatory response syndrome , trauma , or burns . The interventions were computer-assisted insulin protocol ( CAIP ) , with insulin infusion maintaining BG between 100 and 130 mg/dL ; Leuven protocol , with insulin maintaining BG between 80 and 110 mg/dL ; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients ' median BG , and the safety outcome was the incidence of hypoglycemia ( < or=40 mg/dL ) . RESULTS The mean of patients ' median BG was 125.0 , 127.1 , and 158.5 mg/dL for CAIP , Leuven , and conventional treatment , respectively ( P = .34 , CAIP vs Leuven ; P < .001 , CAIP vs conventional ) . In CAIP , 12 patients ( 21.4 % ) had at least one episode of hypoglycemia vs 24 ( 41.4 % ) in Leuven and 2 ( 3.8 % ) in conventional treatment ( P = .02 , CAIP vs Leuven ; P = .006 , CAIP vs conventional ) . CONCLUSIONS The CAIP is safer than and as effective as the st and ard strict protocol for controlling glucose in MICU patients . Hypoglycemia was rare under conventional treatment . However , BG levels were higher than with IV insulin protocol BACKGROUND The dem and for anticoagulant treatment is increasing . We compared the benefits of computer-generated anticoagulant dosing with traditional dosing decided by experienced medical staff in achieving target international normalised ratios ( INRs ) . METHODS In five European centres we r and omly assigned 285 patients in the stabilisation period and stabilised patients to the computer-generated-dose group ( n=137 ) or traditional-dose group ( n=148 ) . Centres had a specialist interest in oral anticoagulation but no previous experience with computer-generated dosing . The computer program calculated doses and times to next visit . Our main endpoint was time spent in target INR range ( Rosendaal method ) . FINDINGS For all patients combined , computer-generated dosing was significantly beneficial overall in achieving target INR ( p=0.004 ) . The mean time within target INR range for all patients and all ranges was 63.3 % ( SD 28.0 ) of days in the computer-generated-dose group compared with 53.2 % ( 27.7 ) in the traditional-dose group . For the stabilisation patients alone , computer-generated doses led to a non-significant benefit in all INR ranges ( p=0.06 ) , whereas in the stable patients the benefit was significant ( p=0.02 ) . INTERPRETATION The computer program gave better INR control than the experienced medical staff and at least similar st and ards to the specialised centres should be generally available . Clinical outcome and cost effectiveness remain to be assessed Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing dem and s for oral anticoagulation . The DAWN AC is one of the most widely used computer-dosage programs . Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of " time in target INR range " ( TIR ) not on clinical safety in practice . A five-year international r and omised clinical study of computer assistance with the DAWN AC program compared with manual dosage in 2,631 patients has been performed at 13 centres with established expertise in oral anticoagulation mainly in the EU . Safety assessment have been based on the comparison of bleeding or thrombotic events with DAWN AC compared with manual dosage in a r and omised study . Safety of the DAWN AC program has been demonstrated . Clinical events of bleeding and thrombosis were almost identical with the experienced manual dosage group . Therapeutic control improved with DAWN AC to 66.8 % from 63.4 % TIR . The program failed to provide a dosage recommendation on only 5.7 % of occasions . At a group of experienced centres with a special interest in oral anticoagulation , the DAWN AC computer-dosage program proved as safe clinical ly as manual dosage by experienced medical staff . With DAWN AC , laboratory control was improved , the difference being highly significant . The results should reassure hospitals and community clinics that the DAWN AC program is safe and facilitate greater and longer provision of warfarin treatment where required To meet growing dem and for oral anticoagulation worldwide there has been increased dependence on computer‐assistance in dosage although the safety and effectiveness of any of the individual computer‐assisted dosage programs has not previously been established . This r and omised multicentre clinical end‐point study assessed a new version of the parma 5 program . It compared parma 5 safety and effectiveness with manual dosage by experienced medical staff at 19 centres with a known interest in oral anticoagulation . Target recruitment was 8000 patient‐years , r and omised to medical staff or parma‐5 assisted dosage . Safety and effectiveness of the parma 5 program was compared with manual dosage . A total of 10 421 patients were recruited ( 15 369 patient‐years ) in the 5‐year study . International normalised ratio ( INR ) tests numbered 167 791 with manual and 160 078 with parma 5 dosage . With parma 5 there was overall a non‐significant reduction in clinical events but in the 2542 patients with deep vein thrombosis/pulmonary embolism , clinical events were significantly reduced ( P = 0·005 ) . Success in achieving ‘ time in target INR range ’ was also significantly greater with parma 5 compared with the dosage by experienced medical staff . This study demonstrated the safety and effectiveness of parma 5‐assisted dosage CONTEXT Most articles in clinical journals are not appropriate for direct application by individual clinicians . OBJECTIVE To create a second order of clinical peer review for journal articles to determine which articles are most relevant for specific clinical disciplines . DESIGN AND SETTING A 2-stage prospect i ve observational study in which research staff review ed all issues of over 110 ( number has varied slightly as new journals were added or discarded from review but number has always been over 110 ) clinical journals and selected each article that met critical appraisal criteria from January 2003 through the present . Practicing physicians were recruited from around the world , excluding Northern Ontario , to the McMaster Online Rating of Evidence ( MORE ) system and registered as raters according to their clinical disciplines . An automated system assigned each qualifying article to raters for each pertinent clinical discipline , and recorded their online assessment s of the articles on 7-point scales ( highest score , 7 ) of relevance and newsworthiness ( defined as useful new information for physicians ) . Rated articles fed an online alerting service , the McMaster Premium Literature Service ( PLUS ) . Physicians from Northern Ontario were invited to register with PLUS and then receive e-mail alerts about articles according to MORE system peer ratings for their own discipline . Online access by PLUS users of PLUS alerts , raters ' comments , article abstract s , and full-text journal articles was automatically recorded . MAIN OUTCOME MEASURES Clinical rater recruitment and performance . Relevance and newsworthiness of journal articles to clinical practice in the discipline of the rating physician . RESULTS Through October 2005 , MORE had 2139 clinical raters , and PLUS had 5892 articles with 45 462 relevance ratings and 44 724 newsworthiness ratings collected since 2003 . On average , clinicians rated systematic review articles higher for relevance to practice than articles with original evidence and lower for useful new information . Primary care physicians rated articles lower than did specialists ( P<.05 ) . Of the 98 physicians who registered for PLUS , 88 ( 90 % ) used it on 3136 occasions during an 18-month test period . CONCLUSIONS This demonstration project shows the feasibility and use of a post-publication clinical peer review system that differentiates published journal articles according to the interests of a broad range of clinical disciplines Ninety-one patients admitted to hospital with acute air-flow obstruction and requiring theophylline therapy were r and omly assigned to either a monitored or a control group . Intravenously administered and subsequent orally administered theophylline dosages for patients in the monitored group were adjusted daily on the basis of each patients 's estimated theophylline clearance ; dosages for control patients were determined by attending physicians , using knowledge of theophylline serum concentrations . During intravenous therapy , fewer monitored than control patients had serum theophylline concentrations in the toxic range ( 18.9 versus 37.8 % , p = 0.04 ) , and during subsequent oral therapy more monitored than control patients had serum theophylline concentrations in the therapeutic range ( 71.1 versus 44.4 % , p = 0.018 ) . There was a trend for peak expiratory flow rates to normalize more quickly in monitored patients , and their mean duration of hospital stay was shorter ( 6.3 versus 8.7 days , p = 0.029 ) . Two patients in the control group died ; both had theophylline concentrations above 25 micrograms/ml and clinical toxicity . No serious side effects were observed in the monitored group . With pharmacokinetic individualization of theophylline dosage , more patients achieved serum concentrations in the therapeutic range , and there was a tendency for more rapid clinical improvement In a prospect i ve , r and omized clinical trial , we compared the accuracy of warfarin dosage-adjustments predictions using a computer program to the skill of an experienced anticoagulation nurse-specialist . The computer program predicts the steady state warfarin dose by applying Bayesian forecasting techniques to a mathematical model of the dynamic pharmacologic response to warfarin . Fifty patients who were receiving chronic warfarin therapy and who required a dosage adjustment because their prothrombin time was greater than or equal to 2 s away from their target prothrombin time were enrolled . The baseline characteristics of each group were similar , including the mean of the absolute value of the differences between initial prothrombin times and corresponding target prothrombin times . After a new a new warfarin dose was predicted , the prothrombin time was measured at least 7 days after dosage adjustment . Overall , the results in each group were comparable . There was no significant difference between groups and the mean of the absolute value of the differences between final prothrombin times and target prothrombin times , nor was there a difference in the proportion of patients who had a final prothrombin time within 2 s of the target prothrombin time . We conclude that the accuracy of warfarin dosage adjustments made using computer modeling is comparable to the skill of an anticoagulation nurse-specialist In two consecutive studies the clinical application and suitability of two computer-assisted data management systems ( Camit and Cadmo ) were evaluated in a prospect i ve manner . In each study nineteen long-st and ing , stable insulin-dependent patients were r and omly assigned to one of two groups . In study I assessment of metabolic control and insulin dose adjustments were based either on the Camit S1 data analysis or on the conventional log-book method , whereas in study II the Camit S2 and the Cadmo simulation programs were evaluated . HbA1c values decreased significantly in both studies ( p < 0.05 ) . A clear decline in hypoglycemic events as well as a significant reduction of the percentage of glucose values below 4.0 mmol/l ( p < 0.005 ) and a marked increase ( p < 0.05 ) in the percentage of glucose levels in the target range ( 4.0 - 10.0 mmol/l ) were observed . We found both computerized assessment systems to be reliable and suitable for the assessment of blood glucose control and for insulin dose finding . The graphical and statistical presentation of the numerous glucose and insulin data allowed a better summary of blood glucose control and metabolic trends . More time could be spent for problem solving , which proved to be much less exhausting with the computer for the attending physician . Further studies should address the educational potential of computerized systems for the patient as well as for the physician 1 . A prospect i ve r and omised trial was conducted to compare aminoglycoside dose prediction based on individually measured pharmacokinetic data , with dosage based on physician intuition . 2 . After 2 days of therapy more patients in the pharmacokinetic group had achieved both peak ( 6 - 10 mg 1(-1 ] and trough ( 1 - 2 mg 1(-1 ] target plasma concentrations ( P = 0.007 ) , peaks alone ( P = 0.01 ) and troughs alone ( P = 0.01 ) . Their mean ( s.e . mean ) peak concentration was 6.49 + /- 0.39 mg 1(-1 ) compared with 4.27 + /- 0.52 mg 1(-1 ) in the control group ( P = 0.001 ) , with trough concentrations of 1.44 + /- 0.22 mg 1(-1 ) and 0.94 + /- 0.21 mg 1(-1 ) respectively ( P = 0.054 ) . 3 . After 5 days of therapy , peak and trough concentrations were still significantly higher in the pharmacokinetic group despite empirical dose adjustment ( P = 0.01 and P = 0.013 respectively ) . 4 . The mean ( s.e . mean ) daily dose of aminoglycoside was higher in the computer group ( 312 + /- 17 mg vs 203 + /- 13 mg , P = 0.001 ) . 5 . These findings suggest that dose estimation based on measured pharmacokinetic parameters is superior at achieving target plasma drug concentrations |
11,171 | 21,063,399 | Conclusions : An array of biomarkers have been identified that correlate with survival following chemoradiotherapy in anal cancer .
However , investigators are yet to identify a biomarker that has the ability to consistently predict outcome in this disease . | Background : Recent decades have seen combination chemoradiotherapy become the st and ard treatment for anal squamous cell carcinoma ( SCC ) .
However , the burden of this disease continues to rise , with only 10 % of patients with metastatic disease surviving > 2 years .
Further insight into tumour characteristics and molecular biology may identify novel therapeutic targets .
This systematic review examines current prognostic markers in SCC of the anus . | BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . PURPOSE The phase III Iressa Survival Evaluation in Lung Cancer ( ISEL ) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer . We analyzed ISEL tumor biopsy sample s to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting . METHODS Biomarkers included epidermal growth factor receptor ( EGFR ) gene copy number by fluorescence in situ hybridization ( n = 370 ) ; EGFR ( n = 379 ) and phosphorylated Akt ( p-Akt ) protein expression ( n = 382 ) by immunohistochemistry ; and mutations in EGFR ( n = 215 ) , KRAS ( n = 152 ) , and BRAF ( n = 118 ) . RESULTS High EGFR gene copy number was a predictor of a gefitinib-related effect on survival ( hazard ratio [ HR ] , 0.61 for high copy number and HR , 1.16 for low copy number ; comparison of high v low copy number HR , P = .045 ) . EGFR protein expression was also related to clinical outcome ( HR for positive , 0.77 ; HR for negative , 1.57 ; comparison of high v low protein expression HR , P = .049 ) . Patients with EGFR mutations had higher response rates than patients without EGFR mutations ( 37.5 % v 2.6 % ) ; there were insufficient data for survival analysis . No relationship was observed between p-Akt protein expression and survival outcome , and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations . CONCLUSION EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL . Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment PURPOSE We have previously shown that loss of BAX expression is a negative prognostic factor in metastatic colorectal cancer . In the present study , we addressed the prognostic relevance of BAX and its upstream regulator p53 in squamous cell carcinoma ( SCC ) of the esophagus . Analysis of p16(ink4a/CDKN2 ) was included because p16(ink4a/CDKN2 ) and p53 were shown previously to cooperate during induction of cell cycle arrest and apoptosis . PATIENTS AND METHODS Retrospective analysis of 53 patients with curative intended R0 resection of esophageal SCC was done . Protein expression of BAX , p53 , and p16(ink4a/CDKN2 ) was investigated by immunohistochemistry . In addition , tumor DNA was screened for BAX frameshift mutations by fragment length analysis and for p53 mutations by single-str and conformation polymorphism-polymerase chain reaction . RESULTS Overall median survival was 13.7 months . Patients with high BAX protein expression had a median survival of 19.5 months versus 8.0 months with low BAX expression ( P < .005 ) . High p16(ink4a/CDKN2 ) protein expression was associated with a median survival of 23.8 months versus 9.7 months with low p16(ink4a/CDKN2 ) ( P = .011 ) . The best survival ( median , 45.8 months ) was seen in a subgroup of 12 patients whose tumors bore the combination of both favorite phenotypes ( ie , high BAX and high p16(ink4a/CDKN2 ) protein expression ) . CONCLUSION In this retrospective investigation , the combined analysis of BAX and p16(ink4a/CDKN2 ) shows subgroups in SCC of the esophagus with favorable ( p16(ink4a/CDKN2)/BAX high expressing ) or poor prognosis ( loss of p16(ink4a/CDKN2)/loss of BAX ) . We suggest that such a multimarker analysis of apoptosis pathways could be useful for individualization of therapeutic strategies in the future , and suggest prospect i ve studies to confirm these results Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal , approximately 20 % of patients will develop a local recurrence . This study examined the prognostic significance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the anal canal Objectives : The incidence of anal cancer among men who have sex with men ( MSM ) has continued to increase since the introduction of highly active antiretroviral therapy ( HAART ) . The prevalence of the putative anal cancer precursor , anal intraepithelial neoplasia ( AIN ) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced . We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART . Design and methods : A baseline point-prevalence analyses in a prospect i ve cohort study of AIN was performed at a university-based research clinic . A total of 357 HIV-positive MSM with no history of anal cancer completed a question naire detailing behaviors and medical history , anal cytology and human papillomavirus ( HPV ) testing , and high-resolution anoscopy with biopsy for detection of AIN . Results : Eighty-one percent of participants with available CD4 + cell counts at baseline had AIN of any grade ; 52 % had AIN 2 or 3 ; and 95 % had anal HPV infection . In multivariate analysis , detection of ≥ 6 HPV types [ odds ratio ( OR ) , 36 ; 95 % confidence interval ( CI ) , 7.4–171 ) and use of HAART ( OR , 10 ; 95 % CI , 2.6–38 ) were associated with AIN after adjustment for length of time participants were HIV-positive , CD4 + cell count and HIV viral load . Conclusions : The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART . Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART PURPOSE To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy ( XRT ) , 5-fluorouracil ( 5-FU ) , and mitomycin C ( MMC ) . METHODS AND MATERIAL S From January 1991 to December 1993 , 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospect ively design ed protocol of XRT ( 24 Gy/12 - -3(1/2 ) wk split--28 Gy/14 ) and concurrent 5-FU ( 1000 mg/m2/day 1 - 4 ) and MMC ( 10 mg/m2 day 1 ) of each cycle of XRT . Paraffin-embedded tumor sample s were unavailable in 9 patients , leaving 49 patients in the study . Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining . Actuarial survival and disease-free survival ( DFS ) rates were estimated by the Kaplan-Meier method , and compared using the log-rank test . A Cox proportional hazard model was used for the multivariable analysis . RESULTS There were 6 T1 , 26 T2 , 7 T3 , and 10 T4 lesions . Primary tumor sizes ranged from 1 - 15 cm with a median of 4 cm . There were 6 patients with nodal metastases . Median follow-up was 4.5 years . Positive nuclear immunostaining for p53 was observed in 40 of 49 patients . The median percent positive staining was 5 % , with 13 , 9 , and 18 patients showing staining in < 5 % , 5 to < 10 % , and 10 - 50 % of tumor nuclei respectively . There was no correlation of percent p53 staining with gender , age , tumor stage , size , or histology . Local , regional , and distant failures were observed in 12 , 2 , and 2 patients respectively . The 5-yr survival and DFS were 84 % and 64 % respectively . In univariate analysis , the only prognostic variable for survival was gender . For DFS , advanced T category and large tumor size were predictive of poor DFS . In multivariate analysis , poor DFS was associated with high T category ( p = 0.0008 ) , basaloid histology ( p = 0.001 ) , male gender ( p = 0.002 ) , and increasing percent of p53 protein expression ( p = 0.01 ) . CONCLUSIONS It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal . For patients managed with combined XRT , 5-FU , and MMC , percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category , gender , and histology Ultimately aim ing at a more individualized therapeutic approach in epidermoid anal cancer , this study explored the prognostic and predictive impact of a set of tumour markers . From a population -based cohort of 276 patients with epidermoid anal cancer , treated according to prospect i ve protocol s , 215 pre-treatment biopsies were investigated using immunohistochemistry . The expression of p53 , p21 , Cyclin A and CD31 was measured semi-quantitatively . The expression rate was classified as high when immunostaining was seen in > 5 % of the tumour cells for p53 and p21 , > 20 % in Cyclin A and , above median vessel count for CD31 . Marker expression was correlated to survival and treatment response . A high Cyclin A expression correlated significantly with improved overall ( 77 % vs 59 % , p = 0.005 ) and tumour-specific ( 81 % vs 64 % , p = 0.009 ) survival at 5 years . Also , the locoregional failure rate was significantly lower in patients with a high Cyclin A expression ( 12 % vs 24 % , p < 0.05 ) . In a multivariate Cox analysis Cyclin A was an independent prognostic factor . A low p21 expression correlated with a reduced rate of locoregional failure ( 14 % vs 27 % , p < 0.05 ) but no impact on survival was found . For p53 and CD31 no significant correlations were obtained . Cyclin A may be an indicator of radiosensitivity and a valuable prognostic marker in epidermoid anal cancer PURPOSE Expression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia ( CLL ) . We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL . PATIENTS AND METHODS Patients had received at least one prior fludarabine-containing regimen and were stratified on the basis of prior fludarabine response , number of prior regimens , and duration of response to last prior therapy . Patients were r and omly assigned to 28-day cycles of fludarabine 25 mg/m2/d plus cyclophosphamide 250 mg/m2/d administered intravenously for 3 days with or without oblimersen 3 mg/kg/d as a 7-day continuous intravenous infusion ( beginning 4 days before chemotherapy ) for up to six cycles . The primary end point was the proportion of patients who achieved complete response ( CR ) or nodular partial response ( nPR ) . RESULTS Of 241 patients r and omly assigned , CR/nPR was achieved in 20 ( 17 % ) of 120 patients in the oblimersen group and eight ( 7 % ) of 121 patients in the chemotherapy-only group ( P = .025 ) . Achievement of CR/nPR was correlated with both an extended time to progression and survival ( P < .0001 ) . In patients who remained sensitive to fludarabine , oblimersen was associated with a four-fold increase in the CR/nPR rate and a significant survival benefit ( P = .05 ) . Oblimersen was frequently associated with thrombocytopenia and , rarely , tumor lysis syndrome and cytokine release reactions ; the incidence of opportunistic infections and second malignancies was similar in both groups . CONCLUSION The addition of oblimersen to fludarabine plus cyclophosphamide significantly increases the CR/nPR rate in patients with relapsed or refractory CLL ( particularly fludarabine-sensitive patients ) , as well as response duration among patients who achieve CR/nPR OBJECTIVES There is lack of consensus regarding concurrent vs. staged approaches , and the prioritisation of staged procedures in cases presenting with colorectal carcinoma ( CRC ) and abdominal aortic aneurysm ( AAA ) synchronously . We aim to present our experience , review the literature on this therapeutic dilemma and examine the role of endovascular aortic repair ( EVAR ) . DESIGN , MATERIAL S AND METHODS An observational study of the experience of two centres and a systematic review of the published literature . RESULTS Twenty-four patients were identified from the prospect i ve data bases of two tertiary referral centres between 2001 and 2006 . Intervention for both malignancy and aneurysm was performed in 13 patients . In 10 patients , cancer resection was performed initially and was followed by open aneurysm repair ( n=3 ) or EVAR ( n=7 ) . Two patients ( AAA diameters : 7.0 and 8.0 cm ) underwent EVAR prior to colonic resection . One patient was selected for synchronous surgery . There were no interval AAA ruptures , graft infection or postoperative mortalities . Literature review identified 269 such cases ; of these 101 were treated by combined surgery . In staged surgery , there were nine interval aneurysmal ruptures and one aortic graft infection . CONCLUSIONS In our experience , staged management can be undertaken , without interval aneurysmal rupture . EVAR has an evolving role in preventing delay in CRC management , in high-risk patients , and during combined intervention BACKGROUND Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has , in uncontrolled studies , yielded similar local tumour control and survival rates to surgery . However , whether the addition of chemotherapy improves outcome without adding to morbidity is not known . Our trial was design ed to compare combined modality therapy ( CMT ) with radiotherapy alone in patients with epidermoid anal cancer . METHODS From 856 patients considered for entry to our multicentre trial , 585 patients were r and omised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4 - 5 weeks ( 290 patients ) or the same regimen of radiotherapy combined with 5-fluorouracil ( 1000 mg/m2 for 4 days or 750 mg/m2 for 5 days ) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin ( 12 mg/m2 ) on day 1 of the first course ( 295 patients ) . We assessed clinical response 6 weeks after initial treatment : good responders were recommended for boost radiotherapy and poor responders for salvage surgery . The main endpoint was local-failure rate ( > or = 6 weeks after initial treatment ) ; secondary endpoints were overall and cause-specific survival . Analysis was by intention-to-treat . FINDINGS In the radiotherapy and CMT arms , respectively , five and three were ineligible , and six and nine died 6 weeks after initial treatment . After a median follow-up of 42 months ( interquartile range 28 - 62 ) , 164 of 279 ( 59 % ) radiotherapy patients had a local failure compared with 101 of 283 ( 36 % ) CMT patients . This gave a 46 % reduction in the risk of local failure in the patients receiving CMT ( relative risk 0.54 , 95 % CI 0.42 - 0.69 , p < 0.0001 ) . The risk of death from anal cancer was also reduced in the CMT arm ( 0.71 , 0.53 - 0.95 , p = 0.02 ) . There was no overall survival advantage ( 0.86 , 0.67 - 1.11 , p = 0.25 ) . Early morbidity was significantly more frequent in the CMT arm ( p = 0.03 ) , but late morbidity occurred at similar rates . INTERPRETATION Our trial shows that the st and ard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin , with surgery reserved for those who fall on this regimen BACKGROUND The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma ( HNSCC ) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospect i ve clinical trial . METHODS We prospect ively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group ( ECOG ) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and st and ard fractionation radiation therapy . The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction ( PCR ) and in situ hybridization . Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis . The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age , ECOG performance status , stage , and other covariables was estimated by use of a multivariable Cox proportional hazards model . All statistical tests were two-sided . RESULTS Genomic DNA of oncogenic HPV types 16 , 33 , or 35 was located within tumor cell nuclei of 40 % ( 95 % confidence interval [ CI ] = 30 % to 50 % ) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR . Compared with patients with HPV-negative tumors , patients with HPV-positive tumors had higher response rates after induction chemotherapy ( 82 % vs 55 % , difference = 27 % , 95 % CI = 9.3 % to 44.7 % , P = .01 ) and after chemoradiation treatment ( 84 % vs 57 % , difference = 27 % , 95 % CI = 9.7 % to 44.3 % , P = .007 ) . After a median follow-up of 39.1 months , patients with HPV-positive tumors had improved overall survival ( 2-year overall survival = 95 % [ 95 % CI = 87 % to 100 % ] vs 62 % [ 95 % CI = 49 % to 74 % ] , difference = 33 % , 95 % CI = 18.6 % to 47.4 % , P = .005 , log-rank test ) and , after adjustment for age , tumor stage , and ECOG performance status , lower risks of progression ( hazard ratio [ HR ] = 0.27 , 95 % CI = 0.10 to 0.75 ) , and death from any cause ( HR = 0.36 , 95 % CI = 0.15 to 0.85 ) than those with HPV-negative tumors . CONCLUSION For patients with HNSCC of the oropharynx , tumor HPV status is strongly associated with therapeutic response and survival BACKGROUND Previous results from our phase 3 r and omised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) at 3 years . Here we report the 5-year survival data , and investigate the relation between cetuximab-induced rash and survival . METHODS Patients with LASCCHN of the oropharynx , hypopharynx , or larynx with measurable disease were r and omly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6 - 7 weeks or radiotherapy plus weekly doses of cetuximab : 400 mg/m(2 ) initial dose , followed by seven weekly doses at 250 mg/m(2 ) . R and omisation was done with an adaptive minimisation technique to balance assignments across stratification factors of Karnofsky performance score , T stage , N stage , and radiation fractionation . The trial was un-blinded . The primary endpoint was locoregional control , with a secondary endpoint of survival . Following discussion s with the US Food and Drug Administration , the data set was locked , except for queries to the sites about overall survival , before our previous report in 2006 , so that an independent review could be done . Analyses were done on an intention-to-treat basis . Following completion of treatment , patients underwent physical examination and radiographic imaging every 4 months for 2 years , and then every 6 months thereafter . The trial is registered at www . Clinical Trials.gov , number NCT00004227 . FINDINGS Patients were r and omly assigned to receive radiotherapy with ( n=211 ) or without ( n=213 ) cetuximab , and all patients were followed for survival . Up date d median overall survival for patients treated with cetuximab and radiotherapy was 49.0 months ( 95 % CI 32.8 - 69.5 ) versus 29.3 months ( 20.6 - 41.4 ) in the radiotherapy-alone group ( hazard ratio [ HR ] 0.73 , 95 % CI 0.56 - 0.95 ; p=0.018 ) . 5-year overall survival was 45.6 % in the cetuximab-plus-radiotherapy group and 36.4 % in the radiotherapy-alone group . Additionally , for the patients treated with cetuximab , overall survival was significantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash ( HR 0.49 , 0.34 - 0.72 ; p=0.002 ) . INTERPRETATION For patients with LASCCHN , cetuximab plus radiotherapy significantly improves overall survival at 5 years compared with radiotherapy alone , confirming cetuximab plus radiotherapy as an important treatment option in this group of patients . Cetuximab-treated patients with prominent cetuximab-induced rash ( grade 2 or above ) have better survival than patients with no or grade 1 rash . FUNDING ImClone Systems , Merck KGaA , and Bristol-Myers Squibb Twenty-one patients with documented squamous cell carcinoma ( SCC ) of the anal canal underwent prospect i ve serial collection of 101 serum sample s for radioimmunoassay of SCC antigen to evaluate regression or progression of disease . Eighteen presented with primary SCC of the anal canal , two with metastatic disease , and one with a recurrence in the perineum . Median follow-up was 18 months . Thirteen of 22 serum sample s were true-positives , and nine of 22 were false-negatives . Four of 79 serum sample s were false-positives and 75 of 79 were true-negatives . The sensitivity of this test is 59 % and the specificity is 95 % , with the accuracy of a positive test being 76 % The aim of this prospect i ve study was to evaluate biological markers , their correlation with response and outcome , and the change in these markers under the influence of preoperative chemotherapy ( PCT ) in patients with a large primary breast cancer . One hundred and thirty-five women were treated with PCT , followed by locoregional therapy and adjuvant treatment . Estrogen receptor ( ER ) , progesterone receptor ( PgR ) , HER-2 , p53 , and cathepsin D were determined by immunohistochemistry ( IHC ) before and after PCT . The overall response ( OR ) was 70 % and the pathologic complete response ( pCR ) was 13 % . Forty-four percent of the patients could be offered breast-conserving surgery ( BCS ) . At a median follow-up of 50 mo the overall survival is 82 % and the disease-free survival is 70 % . No local recurrence ( LR ) has developed following BCS.Invasive ductal carcinoma ( IDC ) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC).P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients ( 74 % vs 53 % ) and ER-positive patients ( 75 % vs 65 % ) , but this difference did not reach statistical significance . A trend toward higher complete pathologic remission rate was seen for ER-negative patients ( p=0.0609 ) . PgR , HER-2 , and cathepsin D were not related to response . The pattern of biological markers did not change with PCT , making repeated determination useless |
11,172 | 27,924,137 | However , some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results , indicating that the microbiota acts like an endocrine organ ( e.g. secreting serotonin , dopamine or other neurotransmitters ) and may control the HPA axis in athletes .
What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides , which is associated with reduced microbiota diversity and functionality ( e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters ) . | Fatigue , mood disturbances , under performance and gastrointestinal distress are common among athletes during training and competition .
The psychosocial and physical dem and s during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal ( HPA ) axes , result ing in the release of stress and catabolic hormones , inflammatory cytokines and microbial molecules .
The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology , including metabolism , endocrine , neuronal and immune function .
The gut microbiome and its influence on host behavior , intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis .
Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition .
For instance , induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus , which have well defined roles in intestinal mucus degradation and immune function .
Diet is known to dramatically modulate the composition of the gut microbiota .
Due to the considerable complexity of stress responses in elite athletes ( from leaky gut to increased catabolism and depression ) , defining st and ard diet regimes is difficult . | Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change . Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression . The animal-based diet increased the abundance of bile-tolerant microorganisms ( Alistipes , Bilophila and Bacteroides ) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia , Eubacterium rectale and Ruminococcus bromii ) . Microbial activity mirrored differences between herbivorous and carnivorous mammals , reflecting trade-offs between carbohydrate and protein fermentation . Foodborne microbes from both diets transiently colonized the gut , including bacteria , fungi and even viruses . Finally , increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat , bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease . In concert , these results demonstrate that the gut microbiome can rapidly respond to altered diet , potentially facilitating the diversity of human dietary lifestyles Background Probiotics are an upcoming group of nutraceuticals cl aim ing positive effects on athlete ’s gut health , redox biology and immunity but there is lack of evidence to support these statements . Methods We conducted a r and omized , double-blinded , placebo controlled trial to observe effects of probiotic supplementation on markers of intestinal barrier , oxidation and inflammation , at rest and after intense exercise . 23 trained men received multi-species probiotics ( 1010 CFU/day , Ecologic ® Performance or OMNi-BiOTiC ® POWER , n = 11 ) or placebo ( n = 12 ) for 14 weeks and performed an intense cycle ergometry over 90 minutes at baseline and after 14 weeks . Zonulin and α1-antitrypsin were measured from feces to estimate gut leakage at baseline and at the end of treatment . Venous blood was collected at baseline and after 14 weeks , before and immediately post exercise , to determine carbonyl proteins ( CP ) , malondialdehyde ( MDA ) , total oxidation status of lipids ( TOS ) , tumor necrosis factor-alpha ( TNF-α ) , and interleukin-6 ( IL-6 ) . Statistical analysis used multifactorial analysis of variance ( ANOVA ) . Level of significance was set at p < 0.05 , a trend at p < 0.1 . Results Zonulin decreased with supplementation from values slightly above normal into normal ranges ( < 30 ng/ml ) and was significantly lower after 14 weeks with probiotics compared to placebo ( p = 0.019 ) . We observed no influence on α1-antitrypsin ( p > 0.1 ) . CP increased significantly from pre to post exercise in both groups at baseline and in the placebo group after 14 weeks of treatment ( p = 0.006 ) . After 14 weeks , CP concentrations were tendentially lower with probiotics ( p = 0.061 ) . TOS was slightly increased above normal in both groups , at baseline and after 14 weeks of treatment . There was no effect of supplementation or exercise on TOS . At baseline , both groups showed considerably higher TNF-α concentrations than normal . After 14 weeks TNF-α was tendentially lower in the supplemented group ( p = 0.054 ) . IL-6 increased significantly from pre to post exercise in both groups ( p = 0.001 ) , but supplementation had no effect . MDA was not influenced , neither by supplementation nor by exercise . Conclusions The probiotic treatment decreased Zonulin in feces , a marker indicating enhanced gut permeability . Moreover , probiotic supplementation beneficially affected TNF-α and exercise induced protein oxidation . These results demonstrate promising benefits for probiotic use in trained men . Clinical trial registryhttp://www . clinical trials.gov , identifier : We have previously shown that voluntary wheel running ( VWR ) attenuates , whereas forced treadmill running ( FTR ) exacerbates , intestinal inflammation and clinical outcomes in a mouse model of colitis . As the gut microbiome is implicated in colitis , we hypothesized that VWR and FTR would differentially affect the gut microbiome . Mice ( 9 - 10/treatment ) were r and omly assigned to VWR , FTR , or sedentary home cage control ( SED ) for 6 wk . VWR were given running wheel access , whereas FTR ran on a treadmill for 40 min/day at 8 - 12 m/min , 5 % grade . Forty-eight hours after the last exercise session , DNA was isolated from the fecal pellets and cecal contents , and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform . Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups ( P < 0.01 ) . Interestingly , the community structures of the three treatment groups clustered separately from each other in both gut regions ( P < 0.05 ) . Contrary to our hypothesis , the α-diversity metric , Chao1 , indicated that VWR led to reduced bacterial richness compared with FTR or SED ( P < 0.05 ) . Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa . Of particular interest , Turicibacter spp . , which has been strongly associated with immune function and bowel disease , was significantly lower in VWR vs. SED/FTR . These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice . These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region OBJECTIVE According to the " antioxidants network " theory , the present study was conducted to evaluate the regulation of an antioxidant blend on intestinal redox status and major microbiota of early-weaned piglets . METHODS Piglets from 15 litters were r and omly allocated by litter to the control group ( suckling normally , fed the basal diet , n = 5 ) , the weaning group ( weaned at age 21 d , fed the basal diet , n = 5 ) , and the repair group ( weaned at age 21 d , fed the basal diet supplemented with an antioxidant blend , n = 5 ) . The redox status and major microbiota in jejunum and colon tracts of 24-d-old piglets were detected , respectively . RESULTS Early weaning result ed in significant decreases in jejunum and colon antioxidant capacities , Lactobacillus and Bifidobacterium counts , and significant increases in levels of jejunum malondialdehyde , colon hydroxyl radicals , jejunum and colon H2O2 , and Escherichia coli counts in piglets . The observed imbalance of the intestinal redox status and microbiota was significantly restored by the antioxidant blend . Interestingly , intestinal selected antioxidative items presented a positive correlation with potential beneficial bacteria and a negative correlation with E. coli . Nevertheless , selected oxidative items and the bacteria presented an inverse relationship in piglets . CONCLUSION Supplementation of the antioxidant blend effectively restored intestinal redox status and microbiota balance in the porcine intestine in response to early weaning stress , enhancing intestinal health and function of piglets In a recent clinical study , we demonstrated in the general population that Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) taken in combination for 30 days decreased the global scores of hospital anxiety and depression scale ( HADs ) , and the global severity index of the Hopkins symptoms checklist ( HSCL-90 ) , due to the decrease of the sub-scores of somatization , depression and anger-hostility spheres . Therefore , oral intake of PF showed beneficial effects on anxiety and depression related behaviors in human volunteers . From there , it is interesting to focus on the role of this probiotic formulation in the subjects with the lowest urinary free cortisol levels at baseline . This addendum presents a secondary analyse of the effects of PF in a sub- population of 25 subjects with urinary free cortisol ( UFC ) levels less than 50 ng/ml at baseline , on psychological distress based on the percentage of change of the perceived stress scale ( PSs ) , the HADs and the HSCL-90 scores between baseline and follow-up . The data show that PF improves the same scores as in the general population ( the HADs global score , the global severity index of the HSCL-90 and three of its sub-scores , i.e. somatization , depression and anger-hostility ) , as well as the PSs score and three other sub-scores of the HSCL-90 , i.e. " obsessive compulsive " , " anxiety " , and " paranoid-ideation " . Moreover , in the HSCL-90 , the score of the Factor 1 , related to anxiety and depression , is significantly improved over time in PF-treated subjects compared with controls . Additional pre clinical data showed that PF formulation does not induce side effects such as addiction or learning and memory impairments , and therefore displays a good safety profile . Complementary hypothetical mechanisms of action are proposed to explain the functioning of the brain-gut axis , particularly the relationship between probiotics and stress-related psychopathologies , such as anxiety and depression The aim of this study was to determine whether consumption of a diet containing 8.5 g carbohydrate ( CHO ) x kg(-1 ) x day(-1 ) ( high CHO ; HCHO ) compared with 5.4 g CHO x kg(-1 ) x day(-1 ) ( control ; Con ) during a period of intensified training ( IT ) would result in better maintenance of physical performance and mood state . In a r and omized cross-over design , seven trained runners [ maximal O(2 ) uptake ( Vo(2 max ) ) 64.7 + /- 2.6 ml x kg(-1 ) x min(-1 ) ] performed two 11-day trials consuming either the Con or the HCHO diet . The last week of both trials consisted of IT . Performance was measured with a preloaded 8-km all-out run on the treadmill and 16-km all-out runs outdoors . Substrate utilization was measured using indirect calorimetry and continuous [U-(13)C]glucose infusion during 30 min of running at 58 and 77 % Vo(2 max ) . Time to complete 8 km was negatively affected by the IT : time significantly increased by 61 + /- 23 and 155 + /- 38 s in the HCHO and Con trials , respectively . The 16-km times were significantly increased ( by 8.2 + /- 2.1 % ) during the Con trial only . The Daily Analysis of Life Dem and s of Athletes question naire showed significant deterioration in mood states in both trials , whereas deterioration in global mood scores , as assessed with the Profile of Mood States , was more pronounced in the Con trial . Scores for fatigue were significantly higher in the Con compared with the HCHO trial . CHO oxidation decreased significantly from 1.7 + /- 0.2 to 1.2 + /- 0.2 g/min over the course of the Con trial , which was completely accounted for by a decrease in muscle glycogen oxidation . These findings indicate that an increase in dietary CHO content from 5.4 to 8.5 g CHO x kg(-1)x day(-1 ) ( 41 vs. 65 % total energy intake , respectively ) allowed better maintenance of physical performance and mood state over the course of training , thereby reducing the symptoms of overreaching The extent to which plasma endotoxin concentrations increased was measured in 89 r and omly selected exhausted runners who required admission to the medical tent for treatment in the 1986 Comrades Marathon ( 89,4 km ) . Eighty-one per cent had concentrations above the upper limit of 0,1 ng/ml ( ' endotoxaemic ' ) , including 2 % above 1 ng/ml ( the reported lethal level in humans ) , and only 19 % had normal levels . There was a negative correlation between plasma endotoxin and plasma anti-endotoxin IgG concentration ( P less than 0,025 ) . Those runners completing the race in less than 8 hours had a significantly lower average endotoxin value than those taking longer than 8 hours ( P less than 0,025 ) . Also 80,6 % of runners ( 58/72 ) with high plasma endotoxin values reported nausea , vomiting and /or diarrhoea , compared with 17,7 % ( 3/17 ; P less than 0,001 ) with low endotoxin values . Elevated plasma endotoxin concentrations of 32 r and omly selected endotoxaemic runners had returned to normal 1 - 3 weeks later , and most of them ( 25/32 ) had increased anti-endotoxin IgG concentrations ( P less than 0,02 ) . Fifty-nine runners r and omly selected in a short run ( 21,1 km ) 3 weeks after the 89,4 km run completed the race without problems and none showed any increase in endotoxin levels . Further studies in this field are warranted , especially the measurement of endotoxin and anti-endotoxin values from commencement of training to full fitness . It is possible that these measurements may prove useful as predictors of an athlete 's or combat soldier 's performance To examine the effect of exercise and heat stress on cytokine production , seven males ( 77 + /- 2 kg ; VO(2peak ) = 4.7 + /- 0.4 L min(-1 ) ) completed two ( 15 degrees C ; CON or 35 degrees C ; HEAT ) 90 min cycling trials at 70 % VO(2peak ) . Blood sample s were collected throughout and analysed for spontaneous , and LPS-stimulated intracellular monocyte cytokine production , plasma cytokine levels , and circulating stress hormone concentration . Plasma epinephrine , norepinephrine , and cortisol concentration were elevated ( P < .05 ) as a result of exercise in CON . HEAT increased ( P < .05 ) epinephrine and norepinephrine levels , however , cortisol concentration was not different between the two trials . Exercise had no effect on the concentration of circulating monocytes spontaneously producing IL-6 , TNF-alpha or IL-1alpha , however , there was a decrease in the amount of TNF-alpha per cell post-compared with pre-exercise . HEAT had no effect on spontaneous intracellular cytokine production . Circulating levels of both IL-6 and TNF-alpha were elevated in HEAT , but not in CON . Upon stimulation with LPS , the concentration of monocytes positive for IL-6 , TNF-alpha , and IL-1alpha production was elevated ( P < .01 ) post- and 2 h post-compared with pre-exercise . Stimulated cells , however , produced less ( P < .05 ) TNF-alpha post-exercise and less ( P < .05 ) TNF-alpha and IL-6 2 h post-exercise . HEAT result ed in an increase ( P < .05 ) in the concentration of stimulated cells positive for TNF-alpha and IL-1alpha , however , did not affect the amount of cytokine produced by stimulated monocytes . These results demonstrate that exercise decreases the amount of cytokine produced by LPS-stimulated monocytes , possibly due to elevated levels of circulating stress hormones . Heat stress did not , however , augment the suppression in the amount of cytokine produced by circulating monocytes upon stimulation , despite elevated catecholamines Increased brain dopamine availability improves prolonged exercise tolerance in the heat . It is unclear whether supplementing the amino-acid precursor of dopamine increases exercise capacity in the heat . Eight healthy male volunteers [ mean age 32 ± 11 ( SD ) years ; body mass 75.3 ± 8.1 kg ; peak oxygen uptake ( $ $ \dot{V}O_{{2peak } } $ $ ) 3.5 ± 0.3 L min−1 ] performed two exercise trials separated by at least 7 days in a r and omised , crossover design . Subjects consumed 500 mL of a flavoured sugar-free drink ( PLA ) , or the same drink with 150 mg kg body mass−1 tyrosine ( TYR ) in a double-blind manner 1 h before cycling to exhaustion at a constant exercise intensity equivalent to 68 ± 5 % $ $ \dot{V}O_{{2peak } } $ $ in 30 ° C and 60 % relative humidity . Pre-exercise plasma tyrosine : large neutral amino acids increased 2.9-fold in TYR ( P < 0.01 ) , while there was no change in PLA ( P > 0.05 ) . Subjects cycled longer in TYR compared to PLA ( 80.3 ± 19.7 min vs. 69.2 ± 14.0 min ; P < 0.01 ) . Core temperature , mean weighted skin temperature , heart rate , ratings of perceived exertion and thermal sensation were similar in TYR and PLA during exercise and at exhaustion ( P > 0.05 ) despite longer exercise time in TYR . The results show that acute tyrosine supplementation is associated with increased endurance capacity in the heat in moderately trained subjects . The results also suggest for the first time that the availability of tyrosine , a nutritional dopamine precursor , can influence the ability to subjectively tolerate prolonged submaximal constant-load exercise in the heat The effectiveness of high performance training should be examined at short intervals in order to recognize overtraining promptly . Field or laboratory tests can usually not be performed with such frequency . Easy-to-measure biological , training-relevant parameters are being sought to use in their place . Since the importance of the sympathetic nervous system for adaptation of stress and the relationship between physical training and the activity of the sympathetic nervous system are well accepted , and since an impairment of the sympathetic nervous system is assumed in an overtraining syndrome , we examined the relevance of nocturnal " basal " urinary excretion of free catecholamines with respect to its practical application : 1 . during a pilot study ( training of road and track cyclists before the 1988 Olympic Games in Seoul ) , 2 . through a 4-week prospect i ve , experimental study in 1989 and 1990 ( middle- and long-distance runners ) , 3 . during the competitive season and winter break of a soccer team between August 1990 and April 1991 . The following hypothesis was made : An overtraining or exhaustion syndrome in athletes may usually be accompanied by at least a 50 % decrease in basal dopamine , noradrenaline and adrenaline excretion . When training is effective or the athletes are not exhausted , the decrease of the excretion rate -- with the exception of dopamine -- is more likely to be lower ( noradrenaline , adrenaline ) . Generalization of these results requires further expansion of the experimental basis The purpose of this study was to examine whether exercise training reduced inflammation and symptomology in a mouse model of colitis . We hypothesized that moderate forced treadmill running ( FTR ) or voluntary wheel running ( VWR ) would reduce colitis symptoms and colon inflammation in response to dextran sodium sulfate ( DSS ) . Male C57Bl/6J mice were r and omized to sedentary , moderate intensity FTR ( 8 - 12 m/min , 40 min , 6 weeks , 5x/week ) , or VWR ( 30 days access to wheels ) . DSS was given at 2 % ( w/v ) in drinking water over 5 days . Mice discontinued exercise 24 h prior to and during DSS treatment . Colons were harvested on Days 6 , 8 and 12 in FTR and Day 8 post-DSS in VWR experiments . Contrary to our hypothesis , we found that moderate FTR exacerbated colitis symptomology and inflammation as measured by significant ( p<0.05 ) increases in diarrhea and IL-6 , IL-1β , IL-17 colon gene expression . We also observed higher mortality ( 3/10 died vs. 0/10 , p=0.07 ) in the FTR/DSS group . In contrast , VWR alleviated colitis symptoms and reduced inflammatory gene expression in the colons of DSS-treated mice ( p<0.05 ) . While DSS treatment reduced food/fluid intake and body weight , there was a tendency for FTR to exacerbate , and for VWR to attenuate , this effect . FTR ( in the absence of DSS ) increased gene expression of the chemokine and antibacterial protein CCL6 suggesting that FTR altered gut homeostasis that may be related to the exaggerated response to DSS . In conclusion , we found that FTR exacerbated , whereas VWR attenuated , symptoms and inflammation in response to DSS BACKGROUND The effects of essential amino acid ( EAA ) supplementation during moderate steady state ( ie , endurance ) exercise on postexercise skeletal muscle metabolism are not well described , and the potential role of supplemental leucine on muscle protein synthesis ( MPS ) and associated molecular responses remains to be eluci date d. OBJECTIVE This r and omized crossover study examined whether EAA supplementation with 2 different concentrations of leucine affected post-steady state exercise MPS , whole-body protein turnover , and mammalian target of rapamycin 1 ( mTORC1 ) intracellular signaling . DESIGN Eight adults completed 2 separate bouts of cycle ergometry [ 60 min , 60 % VO(2)peak ( peak oxygen uptake ) ] . Isonitrogenous ( 10 g EAA ) drinks with different leucine contents [ leucine-enriched (l)-EAA , 3.5 g leucine ; EAA , 1.87 g leucine ] were consumed during exercise . MPS and whole-body protein turnover were determined by using primed continuous infusions of [(2)H(5)]phenylalanine and [1-(13)C]leucine . Multiplex and immunoblot analyses were used to quantify mTORC1 signaling . RESULTS MPS was 33 % greater ( P < 0.05 ) after consumption of L-EAA ( 0.08 ± 0.01%/h ) than after consumption of EAA ( 0.06 ± 0.01%/h ) . Whole-body protein breakdown and synthesis were lower ( P < 0.05 ) and oxidation was greater ( P < 0.05 ) after consumption of L-EAA than after consumption of EAA . Regardless of dietary treatment , multiplex analysis indicated that Akt and mammalian target of rapamycin phosphorylation were increased ( P < 0.05 ) 30 min after exercise . Immunoblot analysis indicated that phosphorylation of ribosomal protein S6 and extracellular-signal regulated protein kinase increased ( P < 0.05 ) and phosphorylation of eukaryotic elongation factor 2 decreased ( P < 0.05 ) after exercise but was not affected by dietary treatment . CONCLUSION These findings suggest that increasing the concentration of leucine in an EAA supplement consumed during steady state exercise elicits a greater MPS response during recovery . This trial is registered at clinical trials.gov as NCT01366924 Regular exercise reduces the risk of cancer and disease recurrence . Yet the mechanisms behind this protection remain to be eluci date d. In this study , tumor-bearing mice r and omized to voluntary wheel running showed over 60 % reduction in tumor incidence and growth across five different tumor models . Microarray analysis revealed training-induced upregulation of pathways associated with immune function . NK cell infiltration was significantly increased in tumors from running mice , whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise . Mechanistic analyses showed that NK cells were mobilized by epinephrine , and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition . Moreover , epinephrine induced a selective mobilization of IL-6-sensitive NK cells , and IL-6-blocking antibodies blunted training-induced tumor suppression , intratumoral NK cell infiltration , and NK cell activation . Together , these results link exercise , epinephrine , and IL-6 to NK cell mobilization and redistribution , and ultimately to control of tumor growth |
11,173 | 18,559,754 | Meta- analysis of outcomes comparing ultrasonic with conventional nonultrasonic surgical instrumentation demonstrates significant improvement of several perioperative outcomes in procedure-specific setting s when ultrasonic instrumentation is used | OBJECTIVE To compare the efficacy and safety of ultrasonic surgical instrumentation with nonultrasonic traditional surgical techniques in various types of surgery . | Abstract . Surgical treatment is considered to be the best therapeutic modality for severe hemorrhoidal disease . Different surgical methods of hemorrhoidectomy aim to decrease pain , bleeding , stenosis and discharge . The aim of this study was to evaluate the efficacy of harmonic scalpel hemorrhoidectomy . During a period of seven months , 54 consecutive patients with third- and fourth-degree hemorrhods were prospect ively r and omized for harmonic scalpel hemorrhoidectomy ( HS ) or Milligan-Morgan procedure ( MM ) . These patients were examined at one , two , and six weeks after the operation . All patients had a lower gastrointestinal investigation prior to operation to exclude other colorectal pathologies . All patients had the same kind of preoperative preparation and analgesia during the postoperative course . Pain was assessed using a visual analog scale from 0 to 10 . Patient satisfaction was defined as decrease or absence of symptoms and return to normal daily activities . HS groups included 29 patients , while the MM group had 25 patients . There as no difference between the groups in terms of age , gender , hemorrhoidal degree and indication for operation . The types of intra-operative anesthesia administered to the two groups were similar . Duration of surgery was significantly higher in the MM group ( p<0.0001 ) . Postoperative hospitalization was longer in the MM group ( p<0.0001 ) , and the pain degree was higher in MM group ( p<0.0001 ) . No significant difference was noted in the overall amount of analgesics used in the two groups at week 1 , although it was significantly higher in the MM group 2 and 3 weeks after the operation . Early complication occurred more frequently in the MM group but overall the difference was not statistically significant . In conclusion , harmonic scalpel hemorrhoidectomy is virtually a bloodless operation with minimal tissue damage . It is associated with significant less postoperative pain and a fast return to normal activity Ultrasonically activated coagulating shears ( CS ) can coagulate and divide blood vessels of up to medium size by a tissue-welding technique . We present an application of CS in hepatic parenchymal transection during liver surgery . Intrahepatic vessels are uncovered by the so-called forceps fracture method , and they are coagulated and divided by CS . Larger vessels are tied only on the preserving side before the application of CS . Although further refinement of the CS tip is needed , this method has the potential to significantly simplify and improve surgical procedures for hepatic parenchymal transection PURPOSE A r and omized trial was undertaken to evaluate and compare stapled hemorrhoidopexy with excisional hemorrhoidectomy in which the Harmonic Scalpel ™ was used . METHODS Patients with Grade III hemorrhoids who were employed during the trial period were recruited and r and omized into two groups : ( 1 ) Harmonic Scalpel ™ hemorrhoidectomy , and ( 2 ) stapled hemorrhoidopexy . All operations were performed by a single surgeon . In the stapled group , the doughnut obtained was sent for histopathologic examination to determine whether smooth muscles were included in the specimen . Operative data and complications were recorded , and patients were followed up through a structured pro forma protocol . An independent assessor was assigned to obtain postoperative pain scores and satisfaction scores at six-month follow-up . Patients were also administered a simple question naire at follow-up to assess continence functions . RESULTS Over a 20-month period , 88 patients were recruited . The two groups were matched for age and gender distribution . No significant difference was identified between the two groups in terms of operation time , blood loss , day of first bowel movement after surgery , and complication rates . Despite a similar parenteral and oral analgesic requirement , the stapled group had a significantly better pain score ( P = 0.002 ) ; these patients also had a significantly shorter length of stay ( P = 0.02 ) , and on average resumed work nine days earlier than the group treated with the Harmonic Scalpel ™ ( 6.7 vs. 15.6 , P = 0.002 ) . Although 88 percent of doughnuts obtained in the stapled group contained some smooth muscle fibers , no association was found between smooth muscle incorporation and postoperative continence function , and as a whole the continence outcomes of the stapled group were similar to those after Harmonic Scalpel ™ hemorrhoidectomy . Finally , at six-month follow-up , patients who underwent the stapled procedure had significantly better satisfaction scores ( P = 0.001 ) . CONCLUSIONS tapled hemorrhoidopexy is a safe and effective procedure for Grade III hemorrhoidal disease . Patients derive greater short-term benefits of reduced pain , shorter length of stay , and earlier resumption to work . Long-term follow-up is necessary to determine whether these initial results are lasting BACKGROUND We used an ultrasonic scalpel ( USS ) and an argon beam coagulator ( ABC ) to test their effectiveness and feasibility in comparison to conventional electrocautery for Internal Thoracic Artery ( ITA ) takedown , time for takedown , number of clips , thermal impact , along with morphological integrity assessed by histology . PATIENTS AND METHODS Ninety-three patients undergoing elective coronary bypass surgery were prospect ively r and omized into three groups . In thirty-one patients , either an ultrasonic scalpel ( USS , group A ) , an argon-beam coagulator ( ABC , group B ) or conventional electrocautery ( CEC , group C ) was used for ITA harvesting . RESULTS Harvest times for ITA takedown using CEC ( 16.7 + /- 6 min ) was significantly faster compared to ABC ( 21.6 + /- 8.1 min ; p = 0.02 ) and USS ( 24.1 + /- 8.1 min ; p < 0.001 ) . There was no significant difference comparing harvest times of USS and ABC ( p = 0.1 ) . The number of hemostatic clips used was significantly lower when using USS ( 5.5 + /- 4.6 clips ) compared to both CEC ( 16.6 + /- 6.2 clips ; p < 0.001 ) and ABC ( 20.4 + /- 6.5 clips ; p < 0.001 ) and significantly lower using CEC compared to ABC ( p < 0.007 ) . There were no significant differences in bleeding points within the tissue bed among the groups ( ABC 11/31 patients , CEC 11/31 patients and USS 12/31 patients ) . CONCLUSION This study demonstrates that dissection of the ITA pedicle can be safely done with USS , ABC , and CEC . However , USS is associated with less hemostatic clip dem and but prolonged harvest time compared it to ABC and CEC ; histological assessment revealed no significant difference when comparing groups and equipment used . A variety in design of the hooks may probably ease ultracision practicability Laparoscopic cholecystectomy is frequently complicated by gallbladder perforation and loss of bile or stones into the peritoneal cavity . The aim of this study was to compare the use of ultrasonic dissection and electrocautery with respect to the incidence of gallbladder perforation and intraoperative consequences Ultrasonic energy has recently been used for surgical cutting and coagulating . A prospect i ve r and omized study was undertaken to determine the effectiveness of ultrasonic energy versus monopolar electrosurgery in human laparoscopic cholecystectomy . Two hundred patients were enrolled and r and omized into two groups of 100 patients each . Group A patients underwent laparoscopic cholecystectomy with monopolar electrocautery . Group B patients underwent laparoscopic cholecystectomy with ultrasonically activated shears . In 18 cases of this group , the cystic artery was coagulated and cut without clips . Subhepatic closed drainage was left for 24 h in patients who were c and i date s for oozing of blood or leakage of bile . The median operating time was 45 min in group A and 37 min in group B. Subhepatic drainage was left in 37 patients of group A and 26 of group B. The median blood loss was 14 ml in group A and 2 ml in group B , while 3 patients of group A and none of group B had bile leakage from the bed of the gallbladder for 1 , 1 , and 6 days , respectively . Postoperative ultrasound examination showed a minor subhepatic fluid collection in 5 patients of group A and in 1 patient of group B. All these collection s were treated without drainage . The length of hospital stay was 1.9 + /- 0.5 days in group A and 1.4 + /- 0.2 days in group B. Postoperative pain scores , nausea , and vomiting were equivalent in both groups . It is concluded that ultrasonically activated coagulating shears are safer , easier to use , faster , and less prone to intraoperative complications and postoperative morbidity than monopolar electrocautery in laparoscopic cholecystectomy Division of the short gastric vessels ( SGV ) is a st and ard component of laparoscopic Nissen fundoplications ( LNF ) at our institution . This study compares our original method of vessel control , multifire clip applier ( MCA ) and sharp division , to the Ultracision Harmonic Scalpel LCS ( LCS ) . Twenty consecutive patients were evaluated in a r and omized prospect i ve fashion . Times for SGV division and estimated blood loss ( EBL ) were recorded . Cost data represent patient charges for use of either the MCA or LCS and the charge for operative time . Use of the LCS produced a significant reduction in the time required for SGV division and in the charges to the patient Background : Conventionally , the pectoralis major myocutaneous flap is raised using electrocautery and /or other sharp instruments . The reported morbidity rate using conventional techniques of flap dissection varies from 16 to 63 percent . The purpose of this study was to consider the feasibility of myocutaneous flap dissection using the harmonic scalpel and to compare operative time , blood loss , drainage volume , and morbidity between patients undergoing flap dissection with the harmonic scalpel and those being treated with electrocautery . Methods : Thirty patients with oral cancer , for whom resection and reconstruction using a pectoralis major myocutaneous flap was planned , were recruited in a prospect i ve , r and omized two-arm trial . Patients in arm I ( n = 15 ) had flap dissection using electrocautery and patients in arm II ( n = 15 ) had flap dissection using the harmonic scalpel . Results : The mean operative duration for flap dissection ( 84 versus 47 minutes ) , blood loss ( 129 versus 36 ml ) , and total drainage volume ( 551 versus 302 ml ) were found to be significantly less in the harmonic scalpel group . Conclusion : The results of the study indicate that it is feasible to dissect pectoralis major myocutaneous flaps using the harmonic scalpel with less operative time , blood loss , drainage volume , and morbidity in comparison with electrocautery OBJECTIVE To compare the safety and effectiveness of laparosonic coagulating shears ( LCS ) and electrosurgery for use in laparoscopically assisted vaginal hysterectomy ( LAVH ) . STUDY DESIGN In this prospect i ve study , patients undergoing LAVH performed by one of the authors from October 1997 to January 1998 were assigned at r and om to the electrosurgery group ( n = 20 ) or the LCS group ( n = 20 ) . Procedures performed with LCS or electrosurgery included coagulation and separation of infundibulopelvic or utero-ovarian round ligaments , vesico-uterine-visceral peritoneal fold dissection , and anterior and posterior colpotomy . Outcome measures were operative time , blood loss , decrease in hemoglobin values , and length of hospitalization . RESULTS The mean operative time ( 90+/-22.9 min versus 80.3+/-17.1 min , P = 0.391 ) , blood loss ( 308+/-167 ml versus 250+/-104 ml , P = 0.11 ) , and hemoglobin decrease ( 1.57+/-0.769 mg/dl versus 1.36+/-0.886 mg/dl , P = 0.55 ) were slightly greater in the LCS group than in the electrosurgery group , although these differences were not statistically significant . The length of hospital stay was similar in the two groups ( 5 days ) . No patients developed serious complications related to electrosurgery or LCS . CONCLUSION Our findings indicate that LCS is as safe and effective as electrosurgery , and may offer an alternative option for patients undergoing LAVH Abstract Background : Division of the short gastric vessels ( SGV ) during laparoscopic Nissen fundoplication ( LNF ) may improve outcome . Several techniques are available for SGV division . The aim of this study was to compare in a prospect i ve r and omized trial bipolar electrocautery with cutting blade versus ultrasonic coagulation of the SGV during LNF . Methods : In all , 86 consecutive patients undergoing LNF were prospect ively r and omized into two similar groups that underwent division of the SGV , respectively , using bipolar cutting forceps ( BPCF ) or harmonic coagulating shears ( HCS ) . Operative time , bleeding episodes , complications , equipment problems , and surgeon 's subjective scoring of satisfaction and ease of use were assessed . Results : Mean ( ±SD ) time for fundic mobilization and division of the SGV was not significantly different between the two groups ( BPCF = 20 ± 12 min vs. HCS = 22 ± 12 min ) . Bleeding events , estimated blood loss , surgeon satisfaction , and subjective ease of use were similar , and no transfusions were required . Complications in the BPCF group included a delayed gastric perforation requiring reoperation and two gastric serosal burns repaired intraoperatively . There was one splenic capsular tear using the HCS and one splenic capsular tear using the BPCF , both of which were controlled intraoperatively . The number of functional equipment problems were few and statistically similar . In the authors ' institution , the per case total costs with capital expenditures amortized over 100 cases indicate savings of approximately $ 202/case with use of the BPCF versus the HCS . Regression analysis demonstrated a significant correlation between body mass index ( BMI ) and total case length and time for division of the SGVs . Conclusions : The BPCF and HCS appear to be equally efficacious for SGV division during LNF . Judicious application of both energy forms and heightened vigilance for gastric serosal injury are required with use of both the BPCF and HCS in cases of tight gastrosplenic adhesions or short SGVs . The BPCF carries a potential cost advantage over the HCS in the authors ' institution . The BMI directly correlates with time required to divide SGVs and total length of LNF BACKGROUND / AIMS Thermal trauma is hypothesized as a major cause of late common bile duct stricture . Dispersion of electric energy through the tissues during electrocautery is not controlled and may cause necrosis even in remote tissues . Changes in liver enzymes may be used as indirect indicators of common bile duct damage , because of the close proximity of these structures in the liver porta . METHODOLOGY Laparoscopic cholecystectomy was performed in 20 patients using a monopolar cutter ( thermal device ) , and in another 20 patients using a harmonic scalpel ( non-thermal device ) . Changes in liver enzymes , as well as histology of gallbladder wall were assessed . RESULTS There was a significant rise in liver enzymes ( AST and ALT ) after surgery in both groups , but postoperative values of these two enzymes were significantly higher in patients operated using the monopolar cutter . There were no significant differences in postoperative levels of hemoglobin and red blood cell count between these two groups . CONCLUSIONS Thermal trauma of the liver parenchyma was significantly greater in patients operated using the monopolar cutter , suggesting possible detrimental effects to the common bile duct This study compared the results of hepatectomy for hepatocellular carcinoma ( HCC ) using an ultrasonic dissector with those of a combination of the crushing clamp and finger fracture techniques . The crushing clamp and finger fracture method was used from 1989 to 1992 in 96 patients ( group 1 ) and the ultrasonic dissector from 1993 to 1994 in 69 patients ( group 2 ) . Data from these two sets of patients were collected prospect ively . The groups were comparable in terms of preoperative liver function , tumour size and stage , and the incidence of cirrhosis . Major hepatectomy was performed in 69 patients ( 72 per cent ) of group 1 and in 52 ( 75 per cent ) of those in group 2 . Use of the ultrasonic dissector result ed in lower mean(s.e.m . ) blood loss ( group 1 3.4(0.4 ) litres versus group 2 2.4(0.2 ) litres , P = 0.02 ) , lower mean(s.e.m . ) blood transfusion requirement ( 2.2(0.2 ) versus 1.2(0.2 ) litres , P = 0.001 ) and more patients not requiring blood transfusion ( 8 per cent of group 1 versus 32 per cent of group 2 , P = 0.0001 ) . Postoperative complications occurred in 45 patients ( 47 per cent ) of group 1 and 19 ( 28 per cent ) of those in group 2 ( P = 0.012 ) . There were no deaths in group 2 whereas the hospital mortality rate in group 1 was 16 of 96 ( 17 per cent ) ( P = 0.0004 ) . A wider tumour‐free resection margin ( mean(s.e.m . ) 1.2(0.1 ) versus 0.9(0.1 ) cm , P<0.05 ) and lower serum bilirubin level throughout the postoperative period were also observed in group 2 patients . The ultrasonic dissector is better than the crushing clamp and finger fracture technique in hepatectomy for HCC The ultrasonic scalpel ( USS ) is a hemostatic surgical instrument used for incising and dissecting tissues . It works by using ultrasonic waves to denature collagen forming a coagulum . This study was design ed to examine the effectiveness of the ultrasonic scalpel in open total abdominal hysterectomies with bilateral salpingo-oophrectomies . This study was a nonr and omized study , with 16 cases of total abdominal hysterectomy with bilateral salpingo-oophorectomy being done with the ultrasonic scalpel , and 21 cases being done with the traditional methods of dissection and ligation . The 2 groups were compared in terms of intraoperative blood loss , time , and cost , as well as in terms of postoperative complication and length of stay . Demographically , no significant differences in age or weight existed among the patients in the 2 operative groups . ( p = 0.71 , p = 0.64 , respectively ) . A statistically significant reduction did occur in the estimated blood loss with the use of the harmonic scalpel ( p = 0.05 ) . No significant differences existed between the 2 patient groups in terms of operative time ( p = 0.77 ) , intraoperative costs ( p = 0.11 ) , or length of hospital stay ( p = 0.45 ) . However , 52 % of the patients in the traditional method group suffered from postoperative complications that included acute myocardial infa rct ion ( N = 1 ) , ileus ( N = 5 ) , urinary retention ( N = 1 ) , urinary incontinence ( N = 1 ) , respiratory failure ( N = 1 ) , and failure to thrive ( N = 1 ) . Only 25 % of the patients undergoing the USS resection suffered from complications . These complications included urinary retention ( N = 2 ) , respiratory failure ( N = 1 ) , and ileus ( N = 1).A statistically significant reduction occurred in estimated blood loss with the use of the USS ( p < 0.05 ) . There is also decreased intraoperative time , as well as decreased postoperative complications and length of stay in this same group ; however , these differences were not statistically significant . Also , more complications are reported in the traditional resection group ( 62 % compared with 31 % ) . It would be beneficial to accrue a higher patient population and study the use of the USS in this procedure as well as other open abdominal procedures H and -assisted laparoscopic total colectomy for ulcerative colitis has allowed less invasive operations in acute severe colitis and poor risk , and has not yet been widely applied for the reason of prolong the operating time in comparison with open surgery . We present the advantages of the use of the LigaSure Atlas vessel sealing for vascular control during laparoscopic surgery . A retrospective study was conducted to compare 15 patients who underwent h and -assisted laparoscopic total colectomy using an ultrasonic coagulator from January 1988 to September 2002 ( US group ) with 18 patients who were operated using LigaSure Atlas ( LS group ) from October 2002 to December 2003 . There was no significant difference in the background factors of patients between both groups . The operating time was 225 + /- 58 min in the LS group and less than 280 + /- 105 min in the US group . Intraoperative blood loss was 91 + /- 22 ml in the LS group and less than 212 + /- 178 ml in the US group . Postoperative bleeding did not occur in the LS group , but occurred in 1 patient in the US group ( 6.6 % ) and this patient required re-operation . Postoperative seroma formation in the abdomen was found in 3 patients of the US group ( 20 % ) . The procedure using LigaSure Atlas reduced the operating time , intraoperative bleeding and operator 's stress in comparison with st and ard ultrasonic coagulation OBJECTIVE To evaluate the endocrinologic profile and reproductive outcome after laparoscopic drilling using a harmonic scalpel for polycystic ovarian syndrome ( PCOS ) in clomiphene-resistant infertile women . STUDY DESIGN We performed a prospect i ve , r and omized study of 34 infertile women with PCOS . Group A ( 17 women ) underwent laparoscopic ovarian drilling using a harmonic scalpel laser . Group B ( control group , 17 women ) underwent laparoscopic ovarian drilling using a neodymium-yttrium-aluminum-garnet laser . Change in the hormonal profile after surgery , ovulation rate and pregnancy rate were compared between groups A and B. RESULTS LH and testosterone serum levels and the LH-FSH ratio showed a statistically significant reduction after surgery , and the spontaneous ovulation rate was 94 % in both groups . The cumulative pregnancy rates within two years of follow-up were 77 % in group A and 60 % in group B. CONCLUSION Laparoscopic ovarian drilling using a harmonic scalpel is an effective treatment for PCOS in clomiphene-resistant , anovulatory women : it results in ovulation and conception without major complications OBJECTIVE Although useful procedures for radial artery harvest have been reported , forearm circulation and collateral perfusion after radial artery harvesting remain unknown . To assess an optimal radial artery harvest technique for forearm circulation , we design ed a prospect i ve r and omized trial . METHODS Ninety patients were divided into 3 groups of 30 patients . Electrocautery , an ultrasonic scalpel , or sharp scissors and hemoclips were used to harvest radial arteries in groups 1 , 2 , and 3 , respectively . The incidences of harvest site pain , numbness , swelling , discomfort , hematoma , and infection were compared . With forearm thermography , recovery times from cooled down 5 degrees back to rest temperature were compared between groups . All patients had postoperative forearm angiography at 1 and 12 months . RESULTS Although there were no differences in the incidences of pain , swelling , and discomfort , the incidence of numbness was significantly lower in group 3 ( P = .003 ) . The temperature recovery time was significantly shorter in group 3 ( P = .0009 ) . On postoperative angiography at 1 month , the incidence of the development of interosseous arteries was significantly higher in group 3 ( 86.7 % ) than in groups 1 ( 23.3 % ) and 2 ( 36.7 % ) . The 12-month study , however , showed that there was no difference among groups ( 73.3 % , 80.0 % , and 93.3 % in groups 1 , 2 , and 3 , respectively ) . CONCLUSIONS These results suggest that sharp dissection with scissors and clips may be better for early postharvest forearm circulation and can decrease the incidence of h and numbness . However , there were no differences among the 3 methods with respect to forearm circulation 12 months after radial artery harvest PURPOSE : The aim of this study was to compare diathermy and Harmonic Scalpel ® hemorrhoidectomy . METHODS : Fifty consecutive patients were r and omly assigned to 2 groups : Group 1 ( diathermy ) and Group 2 ( Harmonic Scalpel ® ) . RESULTS : The median duration of surgery was 10 minutes for both groups . The median number of pethidine injections used for both groups was zero . The median number of oral analgesic tablets taken was 13 by Group 1 and 14 by Group 2 patients . The median number of tubes of lidocaine jelly used was two by Group 1 and three by Group 2 . There was no statistical difference between pain scores recorded by both groups . Five patients in Group 1 developed posthemorrhoidectomy bleedvs . one patient in Group 2 ( P = NS ) . CONCLUSION : Hemorrhoidectomy by Harmonic Scalpel ® is comparable to diathermy hemorrhoidectomy in terms of postoperative pain and complications Abstract PURPOSE : The aim of this study was to compare the outcome of patients receiving hemorrhoidectomy using Harmonic Scalpel ™ , bipolar scissors , and the conventional scissors excision – ligation technique . METHODS : Eighty-six patients with irreducible prolapsing piles were r and omly assigned to receive 1 ) Milligan-Morgan hemorrhoidectomy using scissors excision – ligation technique or 2 ) bipolar scissors hemorrhoidectomy and Harmonic Scalpel ™ hemorrhoidectomy . Neither the patient nor the independent assessor were aware of the technique used at operation . Patients were followed up at 4 and 12 weeks after operation . The measured outcomes included 1 ) operation time ; 2 ) blood loss ; 3 ) postoperative hospital stay ; 4 ) pain score ; 5 ) pain expectation score ; 6 ) date of first bowel movement ; 7 ) number of pethidine injections ; 8) number of dologesic tablets taken ; 9 ) time off work or normal activity ; 10 ) wound healing ; 11 ) satisfaction score ; and 12 ) postoperative complications , including anal stenosis and fecal or flatus incontinence . RESULTS : There was no difference among the three groups in the operation time , hospital stay , pain expectation score , day of first bowel movement , number of dologesic tablets taken , time off work or normal activity , wound healing , and satisfaction score . The complication rate also did not differ in the three groups . Both Harmonic Scalpel ™ hemorrhoidectomy and bipolar scissors hemorrhoidectomy were superior to Milligan-Morgan hemorrhoidectomy in terms of reduced blood loss . Harmonic Scalpel ™ hemorrhoidectomy had the best pain score when compared with bipolar scissors hemorrhoidectomy and Milligan-Morgan hemorrhoidectomy , and patients required significantly less pethidine injection after Harmonic Scalpel ™ hemorrhoidectomy than after Milligan-Morgan hemorrhoidectomy . Although the time required to return to work or normal activity remained similar , patients after Harmonic Scalpel ™ hemorrhoidectomy had the best satisfaction score among the three groups . CONCLUSION : The study shows that Harmonic Scalpel ™ hemorrhoidectomy is as good as bipolar scissors hemorrhoidectomy in terms of reduced blood loss but is superior because it is associated with less postoperative pain and hence , better patient satisfaction . However , these observed benefits are small , and the time off work or normal activity remains similar BACKGROUND Exhaustive hemostasis is essential to successful thyroidectomy . Electrocoagulation to control bleeding has the potential risk of injuring the surrounding structures from lateral dispersion of heat . The Harmonic Scalpel ( HS ) cuts and coagulates simultaneously using mechanical vibration rather than high temperatures . Because its use in thyroidectomies has been limited , we sought to compare procedure parameters and complications of thyroidectomies performed using the HS with those using electrocoagulation . METHODS Sixty patients were r and omized into 2 surgical groups , HS and the st and ard technique using electrocautery and ligatures as the primary hemostatic method . A sample t test or Wilcoxon rank sum test was used to compare the following parameters : operative time , number of ligatures , blood loss , pain intensity , need for extra dose(s ) of analgesic , incidence of recurrent laryngeal nerve palsy , and hypoparathyroidism . RESULTS Both groups of 30 patients were comparable in age , gender , and nature of disease . In 38 patients ( 63 % ) , surgery was performed for benign disease , and in 22 ( 37 % ) , for differentiated carcinoma . Operative time ( arithmetic mean + /- SD ) was 25 minutes less in the HS group ( 96 + /- 23 vs 121 + /- 34 , P = .005 ) . Median number of ligatures in the HS group was 1 ( range , 0 - 7 ) versus 17 ( range , 6 - 28 ) ( P < .001 ) . Mean blood loss , estimated by gauze weight , was less with HS ( 35 + /- 27 mL vs 54 + /- 51 mL , P = .06 ) . Drainage during the first 24 postoperative hours and pain intensity during the first postoperative week were similar in both groups . There were no episodes of persistent nerve palsy or hypoparathyroidism in either group . CONCLUSION The use of HS in thyroidectomies requires less operative time than does electrocoagulation OBJECTIVES Use of the harmonic scalpel in superficial parotidectomy for benign parotid disease has been shown to reduce surgical time as well as intraoperative blood loss . We sought to determine whether similar results could be achieved with the exp and ed use of the harmonic scalpel in parotidectomy for both benign and malignant disease . STUDY DESIGN Retrospective review . METHODS The medical records of all patients undergoing superficial or total parotidectomy from 1999 to 2004 were review ed . Patients were excluded for a history of bleeding disorder , prior facial nerve weakness , or concurrent neck dissection at the time of parotidectomy . RESULTS Forty-four patients underwent harmonic scalpel parotidectomy and 41 patients underwent conventional cold knife parotidectomy ( control group ) . Use of the harmonic scalpel was associated with a significant reduction in intraoperative blood loss ( 38.0 + /- 3.6 mL vs. 66.0 + /- 10.8 mL for controls , P < 0.05 ) and duration of drainage ( 31.80 + /- 2.4 h vs. 39.29 + /- 2.21 h for controls , P < 0.05 ) . Use of the harmonic scalpel in superficial parotidectomy ( n = 35 ) compared to controls ( n = 37 ) was associated with a significant reduction in intraoperative blood loss ( 38.0 + /- 4.23 mL vs. 68.0 + /- 12.0 mL , P < 0.05 ) and reduced incidence of facial nerve injury ( P < 0.05 ) . In patients undergoing total parotidectomy , no significant differences were observed between the harmonic scalpel ( n = 9 ) and control groups ( n = 4 ) in length of surgery , intraoperative blood loss , postoperative drainage , duration of drainage , and facial nerve injury . CONCLUSIONS Use of the harmonic scalpel in the surgical treatment of parotid disease is safe and confers some advantages over conventional methods of parotid dissection In laparoscopic cholecystectomy dissection can be with monopolar electrocautery or with ultrasonic shears , and can start at the triangle of Calot or at the fundus of the gallbladder Abstract Background : The use of ultrasonic dissectors in endoscopic surgery has proved to be of value , particularly for the prevention of bleeding and the reduction of electrical internal burns . This prospect i ve r and omised study was performed in order to evaluate the efficacy , security and cost of using the ultrasonic hook in thyroid surgery . Methods : Thirty-four consecutive euthyroid patients with multinodular goitre for whom a total thyroidectomy was indicated , were r and omly assigned either to group I , Ultracision ® or to group II , conventional hemostasis . Pre- , peri- , and postoperative biochemical , clinical , surgical and economical variables were compared between both groups . Results : The use of the ultrasonic hook result ed in a significant reduction in operating time , blood loss , and maybe in “ transitory hypoparathyroidism ” ; postoperative analgesic consumption was also reduced in this group . Considering the cost , the ultrasonic hook was no more expensive than conventional hemostasis , as long as a minimum of 15 patients shared the initial unit cost of the device . Conclusion : Even if the use of the ultrasonic dissector is not of major interest in terms of patient management or cost-saving in the context of total thyroidectomy , essential advantages reside in significant reductions of operating time , blood loss and organ injury , ( particularly parathyroid).The reduced operating time undoubtedly represents a positive feature of the ultrasonic dissection technique INTRODUCTION : Management of posthemorrhoidectomy pain remains a very unsatisfactory clinical dilemma . Compared with electrocautery and laser , the Harmonic Scalpel ® causes minimal lateral thermal injury during tissue dissection . PURPOSE : The aim of the study was to establish whether decreased lateral thermal injury translated into diminished posthemorrhoidectomy pain . METHODS : A prospect i ve r and omized trial comparing Harmonic Scalpel ® hemorrhoidectomy and electrocautery was undertaken . Fifty consecutive patients were r and omized into two groups : Harmonic Scalpel ® and electrocautery hemorrhoidectomy . The indications included Grade III internal hemorrhoids with external components or Grade IV disease . Patients with additional anorectal pathology ( fissure of fistula ) were excluded , as were patients with neurologic deficits , chronic pain syndrome , and those already taking narcotic analgesics . Pain was assessed using a visual analog scale preoperatively and on postoperative Days 1 , 2 , 7 , 14 , and 28 . Twenty-four-hour narcotic usage ( Hydrocodone , 10 mg ) was recorded on postoperative Days 1 , 2 , 7 , 14 , and 28 . A three-quadrant modified Ferguson hemorrhoidectomy was performed with each patient in the prone jackknife position . RESULTS : Pain in the Harmonic Scalpel ® hemorrhoidectomy group was significantly less than in electrocautery patients on each postoperative day studied . Analgesic requirements were also significantly less in the Harmonic Scalpel ® group on Days 1 , 2 , 7 , and 14 . There was no correlation between postoperative pain and grade of hemorrhoid , status of the surgical incision ( openvs . closed ) , or any other study variable . Fifty-five percent of Harmonic Scalpel ® patients returned to work within one week of surgery , compared with 23 percent of electrocautery patients . CONCLUSION : The study demonstrates significantly reduced postoperative pain after Harmonic Scalpel ® hemorrhoidectomy compared with electrocautery controls . The diminished postoperative pain in the Harmonic Scalpel ® group likely results from the avoidance of lateral thermal injury Background For transanal endoscopic microsurgery , the ultracision Harmonic Scalpel ( UC ) and the multifunctional TEM400 instrument ( T400 ) seem advantageous . This study investigated their clinical use . Methods Prospect i ve analysis of tumor , patient , and operation characteristics was performed for 196 tumor resections per instrument intended for application . Results The T400 instrument was applied in 162 operations , and the UC in 34 operations . Tumor and patient characteristics were similar except for tumor area ( respectively , 7.5 and 17 cm2 ; p = 0.003 ) . Operative time was proportionate to the tumor area ( p < 0.001 ) and inversely proportionate to its distance from the dentate line to the lower margin of the tumor of the UC ( p = 0.002 ) . Application reduced operative time by 26 % ( p = 0.02 , corrected for area ) . Whereas , T400 was always singly sufficient for excision , the UC required T400 application in 50 % of operations , especially for larger tumors ( p = 0.026 ) , with the result that more rectal wall circumference was captured ( p = 0.043 ) . Both groups had similar safety parameters . Conclusions The UC substantially reduced operative time compared with the T400 , but frequently required the T400 for procedure completion . The T400 is always singly sufficient BACKGROUND Thyroid surgery technique has undergone very few changes in the last century . The UltraCision harmonic scalpel ( UHS ) ( Smithfield , RI ) has been widely used in laparoscopic surgery and is documented to be safe and fast for cutting and coagulating tissue . We studied whether the use of the UHS could have advantages in thyroid surgery in terms of operative time , length of hospitalization , morbidity , and general costs . METHOD Our study was a prospect i ve r and omized trial of thyroidectomies and lobectomies performed for benign thyroid diseases in an endocrine surgery unit between February 2001 and July 2002 . Patients were r and omized in two groups : group A ( n=100 ) underwent thyroidectomy using UHS and group B ( n=100 ) with the conventional clamp- and -tie technique . Main outcome measures were demographics , operating time , length of hospitalization , intra- and postoperative complications , sequelae , and general costs . We used the unpaired 2-tailed Student 's t test and the chi2 test to compare the series . RESULTS The two groups were similar in age and sex . Mean + /- SD operative time was shorter in the UHS group compared with the conventional technique group for both lobectomy ( 61 + /- 06 vs. 78 + /- 10 minutes ) and total thyroidectomy ( 86 + /- 20 vs. 101 + /- 16 minutes ) . Length of hospitalization was similar in both groups ( 1.07 vs. 1.15 days ) . We did not find statistical differences between the two techniques regarding transient postoperative complications . There were no deaths , no blood transfusions , no intraoperative complications , and no postoperative definitive sequelae . The global charges for every patient were significantly less in the UHS group ( 985.77 + /- 107.08 euro vs. 1148.40 + /- 153.25 euro ) . CONCLUSION The use of ultrasonically activated shears result ed in a reduction of 15 - 20 % in operative time and was cost-effective compared to the conventional technique group Seroma formation is the most common complication after mastectomy . Among the several known etiological factors the surgical procedure used may be of importance for seroma formation . This prospect i ve study was carried out to evaluate the ultrasonic energy dissection technique and its effect on seroma formation and other complications : 59 patients with operable breast cancer underwent modified radical mastectomy , performed in 30 of them with an Ultracision Harmonic scalpel and in 29 with scissors and electrocautery . In all cases a st and ard level II axillary dissection was performed with scissors . We found no differences in the outcome of surgery . Peroperative bleeding ( median 300 ml , range 100 - 790 vs 300 ml , range 40 - 1400 ) , drain volume ( 585 ml , range 130 - 1455 ) vs 645 ml , range 95 - 1570 ) , seroma formation 50 ( 0 - 580 ) ml vs 105 ( 0 - 3775 ) ml and wound complications were about the same in both groups . In conclusion , neither clinical advantages or disadvantages of the ultrasound dissection technique were found At the end of a long week in the office , you sink back into your chair , reflecting on some of the more memorable patients you cared for and counseled . Through gentle history taking , you discovered that urinary incontinence is the underlying cause of an elderly patient 's increasing social isolation . During a careful physical examination , you detected bruising on the torso of a woman with chronic headaches and began to explore the longst and ing abusive relationship between the woman and her alcoholic partner . You discontinued procainamide therapy in a 72-year-old man who had asymptomatic premature ventricular contractions after myocardial infa rct ion . To prevent bleeding from esophageal varices , you started -blocker therapy in a woman with long-st and ing cryptogenic cirrhosis and portal hypertension . In couples ' therapy , discussing the future quality of life of a middle-aged gay man with human immunodeficiency virus infection , you journeyed through emotionally intense dialogue about advance directives . You presented the risk factors for major and minor bleeding to a 39-year-old woman who was considering warfarin therapy because of recently diagnosed atrial fibrillation and valvular heart disease . You listened to , made diagnoses for , treated , advised , and comforted many patients . Yet there were some hiccoughs in your practice along the way . You stumbled while debating the pros and cons of breast cancer screening with a healthy 48-year-old woman who has been staying current with information on the Internet . You question ed the merits of a personalized walking program suggested to you by a motivated 66-year-old man with severe claudication . Explaining that you wanted to review the best current evidence on these issues , you resolved to address your uncertainties before these patients made their next office visits , in a week 's time . Sighing deeply , you acknowledge that you have little time to read . You subscribe to three journals , which you browse months after they arrive-either when your journal stack becomes precariously high or when your guilt is sufficiently motivational . You sometimes find the conclusions of individual articles conflicting or confusing . You know that some of the decisions and suggestions you made this week , specifically your decisions about stopping procainamide therapy and starting -blocker therapy and your advice about bleeding risks from anticoagulant therapy , were based on the best current research evidence [ 1 - 3 ] . On the other h and , your patients ' inquiries about breast cancer screening and exercise treatment for claudication highlight your need for a concise , current , rigorous synthesis of the best available evidence on each of these topics : in brief , a systematic review [ 4 , 5 ] . Incorporating Research Evidence into Clinical Decision Making The foregoing scenario is familiar to practitioners . In a typical week , we encounter patients with diverse problems ; exercise numerous clinical , interpersonal , and technical skills ; and make many decisions . The factors that affect these decisions and their outcomes are complex . For instance , each patient has unique sociodemographic characteristics , cultural circumstances , and personal preferences . Each physician has unique knowledge , experiences , and values . Moreover , practitioners and their patients make decisions within the context of a rapidly changing health care system that influences the availability , accessibility , and cost of diagnostic tests and therapies [ 6 ] . Timely , useful evidence from the biomedical literature should be an integral component of clinical decision making . If one treatment has been shown to be better than another , we need to know , so that we can recommend the treatment to the appropriate patients . The worldwide effort to develop new tests and treatments , and to determine their usefulness , has never been stronger , and our patients and their families expect us to be fonts of the knowledge that results from this effort [ 7 ] . Unfortunately , it is easy for current best research evidence to pass us by [ 8 ] . We may lack the time , motivation , and basic skills needed to find , critically appraise , and synthesize information , all of which we must do if we are to integrate the results of original studies into our practice . Fortunately , several potent methods are emerging that can greatly enhance our ability to interpret and apply research evidence ; foremost among them is the systematic review . This article begins a series in Annals that will examine systematic review s in detail and explore their many applications . Systematic review s represent the best chance that most practitioners will have to underst and and accurately apply the key signals arising from the robust and increasingly productive search for solutions to medical problems . A properly conducted systematic review faithfully summarizes the evidence from all relevant studies on the topic of interest , and it does so concisely and transparently . What Is a Systematic Review ? Systematic review s are scientific investigations in themselves , with pre-planned methods and an assembly of original studies as their subjects . They synthesize the results of multiple primary investigations by using strategies that limit bias and r and om error [ 9 , 10 ] . These strategies include a comprehensive search of all potentially relevant articles and the use of explicit , reproducible criteria in the selection of articles for review . Primary research design s and study characteristics are appraised , data are synthesized , and results are interpreted . When the results of primary studies are summarized but not statistically combined , the review may be called a qualitative systematic review . A quantitative systematic review , or meta- analysis , is a systematic review that uses statistical methods to combine the results of two or more studies . The term overview is sometimes used to denote a systematic review , whether quantitative or qualitative . Summaries of research that lack explicit descriptions of systematic methods are often called narrative review s. Review articles are one type of integrative publication ; practice guidelines , economic evaluations , and clinical decision analyses are others . These other types of integrative articles often incorporate the results of systematic review s. For example , practice guidelines are systematic ally developed statements intended to assist practitioners and patients with decisions about appropriate health care for specific clinical circumstances [ 11 ] . Evidence -based practice guidelines are based on systematic review s of the literature , appropriately adapted to local circumstances and values . Economic evaluations compare both the costs and the consequences of different courses of action ; the knowledge of consequences that are considered in these evaluations is often generated by systematic review s of primary studies . Decision analyses quantify both the likelihood and the valuation of the expected outcomes associated with competing alternatives . Differences between Systematic and Narrative Review s All review s , narrative and systematic alike , are retrospective , observational research studies and are therefore subject to systematic and r and om error . Accordingly , the quality of a review - and thus its worth-depends on the extent to which scientific review methods have been used to minimize error and bias . This is the key feature that distinguishes traditional narrative review s from systematic review s ( Table 1 ) . If a review is prepared according to the steps outlined in the right column of Table 1 , it is more likely to be systematic and to provide unbiased conclusions . If review methods approximate those found in the middle column of Table 1 , the article is more likely to be a narrative review , and the conclusions are less likely to be based on an unbiased summary of all relevant evidence . Table 1 . Differences between Narrative Review s and Systematic Review s Systematic review s are generated to answer specific , often narrow , clinical questions in depth . These questions can be formulated explicitly according to four variables : a specific population and setting ( such as elderly out patients ) , the condition of interest ( for example , hypertension ) , an exposure to a test or treatment ( such as pharmacologic management ) , and one or more specific outcomes ( such as cardiovascular and cerebrovascular events and mortality ) [ 12 ] . Thus , an example of a well-formulated , clinical ly relevant question is , Does pharmacologic treatment of hypertension in the elderly prevent strokes and myocardial infa rct ions or delay death ? If the question that is driving the review is not clear from the title , abstract , or introduction , or if no methods section is included , the paper is more likely to be a narrative review than a systematic review [ 13 ] . Most narrative review articles deal with a broad range of issues related to a given topic rather than addressing a particular issue in depth [ 9 ] . For example , a narrative review on diabetes ( such as that which might be found in a textbook chapter ) might include sections on the physiology and pathophysiology of carbohydrate , lipid , and protein metabolism ; the epidemiology of and prognosis associated with diabetes ; diagnostic and screening approaches ; and preventive , therapeutic , rehabilitative , and palliative interventions . Thus , narrative review s may be most useful for obtaining a broad perspective on a topic ; they are less often useful in furnishing quantitative answers to specific clinical questions . Narrative review s are appropriate for describing the history or development of a problem and its management . Narrative review s may better describe cutting-edge developments if research is scant or preliminary or if studies are very limited by flawed design or execution [ 13 ] . They may be particularly useful for discussing data in light of underlying theory and context . Narrative review s can draw analogies and can conceptually integrate two independent fields of research , such as The aim of the study was to examine the safety and effectiveness of the Harmonic Scalpel ® for reducing spasm caused by thermal injury during radial artery harvesting . The study sample included 100 c and i date s undergoing coronary artery bypass grafting . In half the patients , radial artery harvesting was performed using the ultrasonic Harmonic Scalpel equipped with coagulating curved shears and a 14 cm scissor-grip h and le and in the other half , hemostatic clips , scissors , and minimal electrocautery were employed . Comparison of outcome between the groups showed that radial artery harvesting with the Harmonic Scalpel was associated with a shorter harvesting time , lower frequency of spasm , larger internal diameter of the radial artery graft , and a significantly reduced need for clips to control bleeding than the st and ard method . In addition , there were no cases of hematoma or superficial wound infection in the arm , and no postoperative reduction in soft touch sensation or objective pin-prick sensation . In conclusion , the Harmonic Scalpel provides excellent control of bleeding without the need for potentially damaging electrocautery , and with a markedly decreased use of hemostatic clips . Harvesting time is also shorter . The minimized thermal injury decreases the rate of radial artery spasm . Further studies using additional objective measures are currently underway to confirm these findings |
11,174 | 27,144,279 | The st and ard-dose tigecycline and comparator groups did not differ significantly in their rates of clinical cure .
However , high-dose tigecycline was more effective than st and ard-dose tigecycline or the comparators for the treatment of HAP .
There was no significant difference in mortality between the st and ard-dose or high-dose regimen and the comparators .
Although the safety profile of st and ard-dose tigecycline was similar to the comparators , the high-dose regimen exhibited more AEs compared with the other groups .
Conclusion : High-dose tigecycline is efficient for the treatment of HAP but is associated with more AEs | Background : Tigecycline is an antibiotic agent with a broad spectrum , which has an antibacterial effect against many multidrug-resistant organisms .
However , its clinical efficacy in the treatment of hospital-acquired pneumonia ( HAP ) is disputed .
Material s and Methods : In this report , a systematic review and meta- analysis were conducted to evaluate the efficacy and safety of tigecycline for the treatment of HAP . | ABSTRACT Tigecycline , a novel glycylcycline antibiotic , exhibits strong activity against gram-positive , gram-negative , aerobic , anaerobic , and atypical bacterial species , including many resistant pathogens , i.e. , vancomycin-resistant enterococci , methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae . The safety and tolerability of tigecycline administered as single or multiple doses or at various infusion rates were explored in three phase 1 , r and omized , double-blind , placebo-controlled studies in healthy subjects . Full pharmacokinetic profiles of tigecycline were determined in two of these studies . Subjects in the single-dose study received 12.5 to 300 mg of tigecycline , which differed with respect to the duration of infusion , subjects ' feeding status , and ondansetron pretreatment . Subjects in the ascending multiple-dose study received 25 to 100-mg doses of tigecycline as a 1-h infusion every 12 h. The variable volume and infusion rate study consisted of administration of 100-mg loading dose of tigecycline , followed by 50 mg every 12 h for 5 days . Serum sample s were analyzed for tigecycline by vali date d high-pressure liquid chromatography or liquid chromatography/t and em mass spectrometry methods . Systemic clearance ranged from 0.2 to 0.3 liters/h/kg , and the tigecycline half-life ranged from 37 to 67 h. Tigecycline had a large volume of distribution ( 7 to 10 liters/kg ) , indicating extensive distribution into the tissues . Food increased the maximum tolerated single-dose from 100 to 200 mg , but the duration of infusion did not affect tolerability . Side effects , mainly nausea and vomiting , which are common to the tetracycline class of antimicrobial agents , were seen in these studies . Tigecycline exhibits linear pharmacokinetics and is safe and well tolerated in the dose ranges examined To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients , a phase 3 , multicenter , r and omized , double-blind , study evaluated 945 patients . Co primary end points were clinical response in clinical ly evaluable ( CE ) and clinical modified intent-to-treat ( c-mITT ) population s at test-of-cure . Cure rates were 67.9 % for tigecycline and 78.2 % for imipenem ( CE patients ) and 62.7 % and 67.6 % ( c-mITT patients ) , respectively . A statistical interaction occurred between ventilator-associated pneumonia ( VAP ) and non-VAP subgroups , with significantly lower cure rates in tigecycline VAP patients compared to imipenem ; in non-VAP patients , tigecycline was noninferior to imipenem . Overall mortality did not differ between the tigecycline ( 14.1 % ) and imipenem regimens ( 12.2 % ) , although more deaths occurred in VAP patients treated with tigecycline than imipenem . Overall , the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population ; this difference appears to have been driven by results in VAP patients 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 Introduction Tigecycline is an established treatment option for infections with multiresistant bacteria ( MRB ) . It retains activity against many strains with limited susceptibility to other antibiotics . Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospect i ve noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals . Material s and methods Data on the full population have been published ; our present analysis focuses on infections caused by MRB . The study population included patients with complicated infections , high disease severity ( APACHE II > 15 : 65 % ) and high MRB prevalence . Most patients had comorbidities , including cardiovascular disease , renal insufficiency , and /or diabetes mellitus . Treatment success was defined as cure/improvement without requirement of further antibiotic therapy . Results Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus ( MRSA ) , 42 vancomycin-resistant Enterococci ( VRE ) and 67 Gram-negative extended beta-lactamase ( ESBL ) producers . Of the MRB sub population , 140 patients received tigecycline monotherapy , 75 were treated with combination regimens . High overall clinical success rates were recorded for MRB infections treated with tigecycline alone ( 94 % ) or in combinations ( 88 % ) ; in detail intraabdominal infections ( monotherapy : 90 % ; combinations : 93 % ) , skin/soft tissue infections ( 93 ; 100 % ) , community-acquired pneumonia ( 100 ; 100 % ) , hospital-acquired pneumonia ( 94,7 ; 72,7 % ) , diabetic foot infections ( 89 ; 33 % ) , blood stream infections ( 100 ; 100 % ) and multiple-site infections ( 92 ; 71 % ) . Conclusions Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity . These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement Introduction The high incidence of multidrug-resistant ( MDR ) bacteria among patients admitted to ICUs has determined an increase of tigecycline ( TGC ) use for the treatment of severe infections . Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed . Our purpose is to investigate TGC safety and efficacy at higher than st and ard doses . Methods We conducted a retrospective study of prospect ively collected data in the ICU of a teaching hospital in Rome . Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed . The safety profile and efficacy of high dosing regimen use were investigated . Results Over the study period , 54 patients ( pts ) received TGC at a st and ard dose ( SD group : 50 mg every 12 hours ) and 46 at a high dose ( HD group : 100 mg every 12 hours ) . Carbapenem-resistant Acinetobacter.baumannii ( blaOXA-58 and blaOXA-23 genes ) and Klebsiella pneumoniae ( blaKPC-3 gene ) were the main isolated pathogens ( n = 79 ) . There were no patients requiring TGC discontinuation or dose reduction because of adverse events . In the ventilation-associated pneumonia population ( VAP ) subgroup ( 63 patients : 30 received SD and 33 HD ) , the only independent predictor of clinical cure was the use of high tigecycline dose ( odds ratio ( OR ) 6.25 ; 95 % confidence interval ( CI ) 1.59 to 24.57 ; P = 0.009 ) whilst initial inadequate antimicrobial treatment ( IIAT ) ( OR 0.18 ; 95 % CI 0.05 to 0.68 ; P = 0.01 ) and higher Sequential Organ Failure Assessment ( SOFA ) score ( OR 0.66 ; 95 % CI 0.51 to 0.87 ; P = 0.003 ) were independently associated with clinical failure . Conclusions TGC was well tolerated at a higher than st and ard dose in a cohort of critically ill patients with severe infections . In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria BACKGROUND Tigecycline is effective in the treatment of complicated skin/skin-structure infection ( cSSSI ) , complicated intraabdominal infection ( cIAI ) , and community-acquired bacterial pneumonia ( CAP ) , but its efficacy in subjects with secondary bacteremia is unknown . METHODS Pooled data from subjects enrolled for treatment of cSSSI , cIAI , or CAP presenting with bacteremia from 7 double-blind and 1 open-label trial of tigecycline compared with vancomycin-aztreonam , imipenem-cilastatin , levofloxacin , vancomycin , or linezolid were analyzed . The primary efficacy end point was the clinical cure rate at the test-of-cure assessment . RESULTS A total of 170 subjects were identified ( 91 tigecycline recipients and 79 recipients of the comparator agent ) . Clinical cure rates were 81.3 % and 78.5 % for tigecycline and the comparator , respectively ( P = .702 ) . Analysis by sex , age , creatinine clearance , infection site , Acute Physiology and Chronic Health Evaluation score , and Fine score demonstrated no significant between-group differences . Clinical cure rates for the most commonly represented pathogens ( Staphylococcus aureus , Streptococcus pneumoniae , and gram-negative species ) were also not significantly different between treatment groups . No decrease in the rate of cure was found in organisms with increasing tigecycline minimum inhibitory concentrations . Nine subjects treated with tigecycline and 1 subject treated with comparator were found to have persistent bacteremia . No clinical ly significant differences in safety parameters were identified . CONCLUSIONS Tigecycline was generally safe and well tolerated in the treatment of secondary bacteremia associated with cSSSI , cIAI , and CAP ; cure rates were similar to comparative st and ard therapies ABSTRACT In a previous phase 3 study , the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin ( imipenem/cilastatin ) . We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia . This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia . Subjects with hospital-acquired pneumonia were r and omized to receive one of two doses of tigecycline ( 150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h ) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection , depending on the r and omization regimen . Clinical response , defined as cure , failure of treatment , or indeterminate outcome , was assessed 10 to 21 days after the last day of therapy . In the clinical ly evaluable population , clinical cure with tigecycline 100 mg ( 17/20 , 85.0 % ) was numerically higher than with tigecycline 75 mg ( 16/23 , 69.6 % ) and imipenem/cilastatin ( 18/24 , 75.0 % ) . No new safety signals with the high-dose tigecycline were identified . A numerically higher clinical response was observed with the 100-mg dose of tigecycline . This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC ( AUC/MIC ratio ) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia . Further studies are necessary . ( The Clinical Trials.gov identifier for this clinical trial is NCT00707239 . This large prospect i ve non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals . Sixty-five percent of the patients had APACHE II scores > 15 , indicating high overall disease severity . Complicated intra-abdominal infections ( cIAI ) or complicated skin and skin tissue infections ( cSSTI ) were the most common indications , with Staphylococcus aureus , Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens . Clinical success was reported at the end of tigecycline therapy in 74.2 % of the total population , in 75.4 % of the cIAI and in 82.2 % of the cSSTI patients . The sub population ( 28.0 % of the patients ) infected with multidrug-resistant pathogens ( methicillin-resistant S. aureus , extended-spectrum β-lactamase producers and vancomycin-resistant enterococci ) were treated with similar success rates as the overall population . Tigecycline was generally well tolerated . Drug-related adverse events ( AEs ) were reported in 7.7 % of the total population ; 2.5 % had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease . Mortality rates were consistent with the types of infection and severity of illness . There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses . In this large non-interventional study performed in the clinical routine setting , tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile ABSTRACT Patients with intra-abdominal infections differ with regard to the type of infection and the severity of illness . However , the impact of these factors , together with differences in drug exposure , on clinical response is not well understood . Using phase 2 and 3 data for patients with complicated intra-abdominal infections , the relative importance of tigecycline exposure , host factors , and disease factors , alone or in combination , for the probability of clinical response was examined . Patients with complicated intra-abdominal infections who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for 5 to 14 days and who had adequate clinical , pharmacokinetic , and response data were evaluated . Multivariable logistic regression was used to identify factors associated with clinical response . A final multivariable logistic regression model demonstrated six factors based on 123 patients to be predictive of clinical success : a weight of < 94 kg ( P = 0.026 ) , the absence of Pseudomonas aeruginosa in baseline cultures ( P = 0.021 ) , an APACHE II score of < 13 ( P = 0.029 ) , non-Hispanic race ( P = 0.005 ) , complicated appendicitis or cholecystitis ( P = 0.004 ) , and a ratio of the area under the concentration-time curve ( AUC ) to the MIC ( AUC/MIC ratio ) of ≥3.1 ( P = 0.003 ) . The average model-predicted probability of clinical success when one unfavorable factor was present was 0.940 . This probability was lower ( 0.855 ) when the AUC/MIC ratio was < 3.1 and the remaining five factors were set to the favorable condition . The average model-predicted probability of clinical success in the presence of two unfavorable factors was 0.594 . These findings demonstrated the impact of individual and multiple factors on clinical response in the context of drug exposure BACKGROUND Tigecycline , a broad-spectrum antibiotic used for treating serious bacterial infections in adults , may be suitable for pediatric use once an appropriate dosage is determined . OBJECTIVE The aim of this study was to assess the pharmacokinetic ( PK ) properties , safety profile , and descriptive efficacy of tigecycline . METHODS In this Phase II , multicenter , open-label clinical trial , children aged 8 to 11 years with community-acquired pneumonia ( CAP ) , complicated intra-abdominal infection ( cIAI ) , or complicated skin and skin structure infections ( cSSSI ) were administered tigecycline 0.75 , 1 , or 1.25 mg/kg . RESULTS A total of 58 patients received ≥ 1 dose of tigecycline ( 31 boys ; 44 white ; mean age , 10 years ; mean weight , 35 kg ) ; 47 had data from sample s available for PK analysis . The mean ( SD ) PK values were : C(max ) , 1899 ( 2954 ) ng/mL ; T(max ) , 0.56 ( 0.18 ) hour ; between-dose AUC , 2833 ( 1557 ) ng · h/mL ; weight-normalized clearance , 0.503 ( 0.293 ) L/h/kg ; and Vd(ss ) , 4.88 ( 4.84 ) L/kg . Overall clinical cure rates at test-of-cure were 94 % ( 16/17 ) , 76 % ( 16/21 ) , and 75 % ( 15/20 ) in the 0.75- , 1- , and 1.25-mg/kg cohorts , respectively . The rates of protocol violations were higher in the 1- and 1.25-mg/kg groups , result ing in higher proportions of indeterminate clinical cure assessment s relative to the 0.75-mg/kg cohort ( 19 % and 15 % vs 0 % ) . The most frequent adverse event was nausea , which occurred in 50 % of patients overall ( 29/58 ) and the prevalence of which was significantly higher in the 1.25-mg/kg group versus the 0.75-mg/kg group ( 65 % vs 18 % ; P = 0.007 ) . Pharmacodynamic simulations using MIC data from an ongoing microbiological surveillance trial predicted that a dosage of 1.2 mg/kg q12h would lead to therapeutic target attainment levels of up to 82 % for the target AUC(0 - 24)/MIC ratios . CONCLUSION A tigecycline dosage of ∼1.2 mg/kg q12h may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections . Clinical Trials.gov identifier : NCT00488345 |
11,175 | 30,144,191 | RESULTS The systematic review suggested that sustained attention and driving abilities were impaired during hangover .
The research literature suggests that alcohol hangovers may involve impaired cognitive functions and performance of everyday tasks such as driving | BACKGROUND AND AIMS Studies examining the next-day cognitive effects of heavy alcohol consumption have produced mixed findings , which may reflect inconsistencies in definitions of ' hangover ' .
Recent consensus has defined hangover as ' mental and physical symptoms , experienced the day after a single episode of heavy drinking , starting when blood alcohol concentration ( BAC ) approaches zero ' .
In light of this , we aim ed to review the literature systematic ally to evaluate and estimate mean effect sizes of the next-day effects of heavy alcohol consumption on cognition . | OBJECTIVE This study aim ed to investigate the effects of a stressor , white noise , on cognitive performance of subjects in the compromised hangover state . METHOD The study followed a mixed factorial , counterbalanced , repeated- measures design with noise , order of testing , and time of testing as between- participants factors and state during testing as a within- participants factor . Seventy-eight participants performed memory and psychomotor tasks the morning after a regular night of drinking and the morning after a night of no alcohol consumption . Forty-eight participants were tested in the no-noise condition , and the other 30 participants had an additional factor of white noise during both testing sessions . Measures of memory and psychomotor performance are reported . RESULTS The stressor ( white noise ) result ed in poorer memory performance only when participants had consumed alcohol the night before testing ( F = 7.45 , 1/66 df , p < .01 ) . Stress also had a detrimental effect on simple reaction time the morning after alcohol consumption in both the task with regular interstimulus interval ( F = 4.61 , 1/65 df , p < .05 ) and irregular interstimulus interval ( F = 4.45 , 1/65 df , p < .05 ) . The five-choice reaction time task revealed that initial move time and return time were slowed by stress and following a night of intoxication , but these factors did not interact . Stress interacted with time of testing and state in the measure of decision time , indicating that noise has a detrimental effect during the hangover state early in the morning and a detrimental effect during the no-hangover state early in the afternoon . CONCLUSIONS The addition of a stressor results in a significant deterioration in memory and psychomotor performance when persons are in the compromised hangover condition BACKGROUND Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks . We studied this phenomenon , using a dual-task paradigm , involving performance of a visual oddball ( VO ) task while driving in an alcohol challenge paradigm . Previous functional MRI ( fMRI ) studies of the VO task have shown activation in the anterior cingulate , hippocampus , and prefrontal cortex . Thus , we predicted dose-dependent decreases in activation of these areas during VO performance . METHODS Forty healthy social drinkers were administered 3 different doses of alcohol , individually tailored to their gender and weight . Participants performed a VO task while operating a virtual reality driving simulator in a 3 T fMRI scanner . RESULTS Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance , primarily in hippocampus , anterior cingulate , and dorsolateral prefrontal areas , with the least activation occurring during the high dose . Behavioral analysis showed a dose-dependent linear increase in reaction time , with no effects associated with either correct hits or false alarms . In all dose conditions , driving speed decreased significantly after a VO stimulus . However , at the high dose this decrease was significantly less . Passenger-side line crossings significantly increased at the high dose . CONCLUSIONS These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions , which are involved with attentional processing/decision-making . Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving Summary 31 healthy male students were given a placebo and two different doses of alcohol ( on different occasions and in r and om order ) . Choice-reaction-time , tapping-speed , bimanual h and -coordination , critical fusion frequency , st and ing steadiness , Bourdon 's test , blood and urine alcohol content were measured before and 30 , 60 and 90 min after drinking . Self-ratings of mood were made . 7 of the subjects were also examined after 2 , 3 and 13 hours and altogether 4 doses of alcohol were used for this group . 24 subjects were given an additional dose of alcohol 2 hours after the first one and the tests were repeated 30 , 60 and 90 min after the additional dose . The agreement between blood and urine alcohol levels was good and the alcohol curves showed an approximately linear fall-off . For the highest alcohol dose used there was a good agreement between blood alcohol level and test performance . The impairment of performance was most marked after 30–60 min . After 2 hours the impairment was very slight . The performance on Choice reaction time and Coordination was related to blood alcohol level also after a smaller dose . Statistically significant changes were obtained in most tests after the highest dose ( 0.8 g per kg body weight ) and in Choice reaction time and Coordination after the smaller dose ( 0.4 g per kg body weight ) . No significant effects were obtained after administration of placebo AIM To assess the effects of binge drinking on students ' next-day academic test-taking performance . DESIGN A placebo-controlled cross-over design with r and omly assigned order of conditions . Participants were r and omized to either alcoholic beverage [ mean = 0.12 g% breath alcohol concentration ( BrAC ) ] or placebo on the first night and then received the other beverage a week later . The next day , participants were assessed on test-taking , neurocognitive performance and mood state . PARTICIPANTS A total of 196 college students ( > or=21 years ) recruited from greater Boston . SETTING The trial was conducted at the General Clinical Research Center at the Boston Medical Center . MEASUREMENTS The Graduate Record Examinations(c ) ( GREs ) and a quiz on a lecture presented the previous day measured test-taking performance ; the Neurobehavioral Evaluation System ( NES3 ) and the Psychomotor Vigilance Test ( PVT ) measured neurocognitive performance ; and the Profile of Mood States ( POMS ) measured mood . FINDINGS Test-taking performance was not affected on the morning after alcohol administration , but mood state and attention/reaction-time were affected . CONCLUSION Drinking to a level of 0.12 g% BrAC does not affect next-day test-taking performance , but does affect some neurocognitive measures and mood state Response differences following administration of alcohol between adult males with a positive ( FHP ) versus negative ( FHN ) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism . If this is so , the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol . We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes . The data reported here are based on an extended data collection period of 3 to 18 hr postingestion , following completion of the acute laboratory portion of the study . Specifically , in the present study , dose-effect timecourse functions for a variety of physiological ( heart rate , blood pressure , and breath alcohol level ) , subjective ( analog mood , drug effect , and withdrawal , Subjective High Assessment Scale ( SHAS ] , and psychomotor measures ( Digit Symbol Substitution Test and numeric recall ) were examined in FHP and FHN college-aged males for secobarbital ( 0 , 100 , 200 mg daily ) and ethanol ( 1 g/kg daily ) . FHP and FHN subjects were matched on light-to-moderate drinking patterns , anthropometric dimensions , age , years of schooling , and drug use . FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects . ( ABSTRACT TRUNCATED AT 250 WORDS Twelve healthy young men were assessed in each of four experimental conditions presented in a Latin Square design : 8-hr time in bed ( TIB ) and placebo , 4-hr TIB and placebo , 8-hr TIB and ethanol , and 4-hr TIB and ethanol . After consuming ethanol ( 0.6 g/kg ) or placebo ( 0900 - 0930 hr ) with 20 % supplements at 1030 and 1100 hr , subjects were tested for sleepiness ( Multiple Sleep Latency Test at 1000 , 1200 , 1400 , and 1600 hr ) and divided attention ( 1030 hr ) performance on day 1 , and for simulated driving and divided attention ( 1000 - 1200 and 1400 - 1600 hr ) performance on day 2 . In the morning testing , with breath ethanol concentrations ( BECs ) averaging 0.049 % , sleepiness was increased , divided attention reaction times increased ( on both days ) , and simulated driving performance was disturbed in the ethanol and 4-hr TIB relative to placebo . Similarly in the afternoon , with BECs averaging 0.013 % , the ethanol and 4-hr TIB condition increased sleepiness and disrupted divided attention and simulated driving performance . The results show that sleepiness and low-dose ethanol combine to impair simulated automobile driving , an impairment that extends beyond the point at which BEC reaches zero . They provide a possible explanation for the incidence of alcohol-related automobile accidents at low BECs Research indicates that glucocorticoids affect hippocampal function and the form of cognition that the hippocampus is thought to subserve , explicit memory . However , some studies suggest that glucocorticoids affect the frontal lobe , attention and working memory . Thus , it is not clear whether glucocorticoids specifically target the hippocampus and explicit memory or if the effects are more ubiquitous . By simultaneously measuring event-related potentials and behavioral performance in tasks design ed to tap particular cognitive and neural processes , the present study examined the effects of hydrocortisone on 24 healthy humans . In an intentional face recognition memory task where the stimuli were presented again after a brief delay ( 6–18 s ) and a long delay ( 30 min ) , hydrocortisone altered the P600 component ( an electrophysiological index of recognition memory and hippocampal activity ) following the brief delay and impaired behavioral performance after the long delay . ERPs and behavioral performance were not affected in the attention and working memory tasks . These findings are consistent with reports indicating that glucocorticoids affect explicit memory and hippocampal function The duration of behavioral impairment after marijuana smoking remains a matter of some debate . Alcohol and marijuana are frequently used together , but there has been little study of the effects of this drug combination on mood and behavior the day after use . The present study was design ed to address these issues . Fourteen male and female subjects were each studied under four conditions : alcohol alone , marijuana alone , alcohol and marijuana in combination , and no active treatment . Mood and performance assessment s were made during acute intoxication and twice the following day ( morning and mid-afternoon ) . Acutely , each drug alone produced moderate levels of subjective intoxication and some degree of behavioral impairment . The drug combination produced the greatest level of impairment on most tasks and “ strong ” overall subjective ratings . There were few significant interactions between the two drugs , indicating that their effects tended to be additive . Only weak evidence was obtained for subjective or behavioral effects the day after active drug treatments , although consistent time-of-day effects ( morning versus afternoon ) were observed on several subjective and behavioral measures . In sum , this study provided little evidence that moderate doses of alcohol and marijuana , consumed either alone or in combination , produce behavioral or subjective impairment the following day OBJECTIVE To examine the effect of previous-day excessive alcohol consumption on laparoscopic surgical performance . DESIGN Study 1 was a r and omized controlled trial . Study 2 was a cohort study . SETTING Surgical skills laboratory . PARTICIPANTS Sixteen science students ( laparoscopic novices ) participated in study 1 . Eight laparoscopic experts participated in study 2 . INTERVENTIONS All participants were trained on the Minimally Invasive Surgical Trainer Virtual Reality ( MIST-VR ) . The participants in study 1 were r and omized to either abstain from alcohol or consume alcohol until intoxicated . All study 2 subjects freely consumed alcohol until intoxicated . Subjects were assessed the following day at 9 am , 1 pm , and 4 pm on MIST-VR tasks . MAIN OUTCOME MEASURES Assessment measures included time , economy of diathermy use , and error scores . RESULTS In study 1 , both groups performed similarly at baseline , but the alcohol group showed deterioration on all performance measures after alcohol consumption . Overall , although the time score differences between the 2 groups were not statistically significant ( P = .29 ) , there was a significant difference between the 2 groups ' diathermy ( P < .03 ) and error ( P < .003 ) scores . There was also a significant effect for time of testing ( P < .003 ) , diathermy ( P < .001 ) , and errors ( P < .001 ) . In study 2 , experts demonstrated a similar postalcohol performance decrement for time ( P < .02 ) , diathermy ( P < .001 ) , and error scores ( P < .001 ) . CONCLUSION Excessive consumption of alcohol appeared to de grade surgical performance the following day even at 4 pm , suggesting the need to define recommendations regarding alcohol consumption the night before assuming clinical surgical responsibilities BACKGROUND This study assessed the effects of heavy drinking with high or low congener beverages on next-day neurocognitive performance , and the extent to which these effects were mediated by alcohol-related sleep disturbance or alcoholic beverage congeners , and correlated with the intensity of hangover . METHODS Healthy heavy drinkers age 21 to 33 ( n = 95 ) participated in 2 drinking nights after an acclimatization night . They drank to a mean of 0.11 g% breath alcohol concentration on vodka or bourbon one night with matched placebo the other night , r and omized for type and order . Polysomnography recordings were made overnight ; self-report and neurocognitive measures were assessed the next morning . RESULTS After alcohol , people had more hangover and more decrements in tests requiring both sustained attention and speed . Hangover correlated with poorer performance on these measures . Alcohol decreased sleep efficiency and rapid eye movement sleep , and increased wake time and next-day sleepiness . Alcohol effects on sleep correlated with hangover but did not mediate the effects on performance . No effect of beverage congeners was found except on hangover severity , with people feeling worse after bourbon . Virtually no sex differences appeared . CONCLUSIONS As drinking to this level affects complex cognitive abilities , safety could be affected , with implication s for driving and for safety-sensitive occupations . Congener content affects only how people feel the next day so does not increase risk . The sleep disrupting effects of alcohol did not account for the impaired performance so other mechanisms of effect need to be sought . As hangover symptoms correlate with impaired performance , these might be contributing to the impairment AIMS To determine the incidence and covariates of hangover following a night of moderate alcohol consumption at a targeted breath alcohol level . DESIGN Data were combined from three r and omized cross-over trials investigating the effects of heavy drinking on next-day performance . A total of 172 participants received either alcoholic beverage ( mean=0.115 g% breath alcohol concentration ) or placebo on one night and the other beverage a week later . The next day , participants completed a hangover scale . PARTICIPANTS Participants were 54 professional merchant mariners attending a recertification course at Kalmar Maritime Academy ( Kalmar , Sweden ) and 118 university students or recent graduates recruited from greater Boston . SETTING One trial was conducted at Kalmar Maritime Academy ( Sweden ) ; the other two were conducted at the General Clinical Research Center at Boston Medical Center . MEASUREMENTS A nine-item scale assessed hangover . FINDINGS Hangover was reported by 76 % of participants . Neither alcoholic beverage type nor participant characteristics was associated with incidence of hangover . CONCLUSIONS Our findings on the propensity of hangover suggest that 25 - 30 % of drinkers may be resistant to hangover OBJECTIVE The effects of an evening of heavy drinking on next-day occupational performance are mixed across studies and have not been investigated for ship-h and ling performance . Furthermore , it is not known whether the residual effects of alcohol on next-day performance are due to its effects on sleep . METHOD Merchant marine cadets ( N=61 ) who had been trained on a diesel power plant simulator and who drank heavily at least episodically were given placebo beer one evening and were r and omized on a second evening to placebo or real beer that result ed in a mean breath alcohol concentration ( BrAC ) of .115 g% . After an 8-hour sleep period , a meal , and a return to < or = .02 g% BrAC , cadets were assessed with self-report measures and the power plant simulator . RESULTS No effects of beverage condition were seen on actual performance , although cadets who consumed alcohol rated their performance as impaired compared with the placebo conditions . Alcohol consumption also increased the Acute Hangover Scale score , improved perceived sleep quality , and decreased perceived latency to sleep onset while not affecting perceived sleep duration . CONCLUSIONS While residual alcohol effects are found on some complex performance tasks , residual effects of .11 to .12 g% BrAC were not seen on ship engine simulator performance despite increased hangover symptoms and perceived impairment from the hangover . Therefore , this level of heavy drinking might not be deleterious to next-day routine occupational performance by young ship engineers despite the subjective ill effects . The perception that alcohol improves sleep onset might be a motivation for some to drink heavily . The effects on older engineers , at higher alcohol levels , and on other ship-h and ling tasks still need to be studied OBJECTIVE To determine if older pilots forgot more about a learned flight task after a 10-month delay than did younger pilots and if the anticipated greater skill loss led older pilots ' performance to be more disrupted by alcohol . DESIGN Repeated measures comparative group design examining the effects of alcohol versus placebo in two age groups ( younger and older ) and at two timepoints : acute intoxication , at a Blood Alcohol Concentration ( BAC ) of 0.10 % , and 8 hours post-drink . SETTING University medical center research laboratory . SUBJECTS Fourteen younger ( mean age = 27 ; SD = 4.21 ; range 21 - 34 ) and 13 older ( mean age = 60 ; SD = 6.27 ; range 51 - 69 ) pilots , recruited from local flying clubs , with current FAA medical certificates . METHODS We examined the effects of alcohol versus placebo in the two age groups and at two times , ie , acute intoxication ( target BAC 0.10 % ) and 8-hour post-drink . Subjects flew a Frasca 141 simulator in a flight task that they had previously learned but not practice d for several months . After completing a baseline flight , pilots were tested during either an alcohol or a placebo condition at the two timepoints . The main outcome measure was a composite measure of flight performance based upon the mean of eight component st and ardized scores from different aspects of the flight task . RESULTS We found detrimental effects of alcohol on the main outcome measure both at the acute and 8-hour post-drink testing . There was also no significant difference between the older and younger pilots ' performance of the flight task or in susceptibility to alcohol either while intoxicated or during hangover . CONCLUSIONS This study replicates the findings of earlier studies that an 8-hour waiting period from " Bottle-to-Throttle " is insufficient but finds little difference according to age in re collection of a previously learned task or in susceptibility to either acute or hangover effects of alcohol A hangover is characterized by the constellation of unpleasant physical and mental symptoms that occur between 8 and 16 h after drinking alcohol . We evaluated the effects of experimentally-induced alcohol hangover on cognitive functions using the Luria-Nebraska Neuropsychological Battery . A total of 13 normal adult males participated in this study . They did not have any previous histories of psychiatric or medical disorders . We defined the experimentally-induced hangover condition at 13 h after drinking a high dose of alcohol ( 1.5 g/kg of body weight ) . We evaluated the changes of cognitive functions before drinking alcohol and during experimentally-induced hangover state . The Luria-Nebraska Neuropsychological Battery was administrated in order to examine the changes of cognitive functions . Cognitive functions , such as visual , memory , and intellectual process functions , were decreased during the hangover state . Among summary scales , the profile elevation scale was also increased . Among localization scales , the scores of left frontal , sensorimotor , parietal-occipital dysfunction , and right parietal-occipital scales were increased during the hangover state . These results indicate that alcohol hangovers have a negative effect on cognitive functions , particularly on the higher cortical and visual functions associated with the left hemisphere and right posterior hemisphere Alcohol intoxication and hangover were studied in 12 healthy male subjects who participated in three 18-h experimental sessions ; two sessions , in which they consumed 1.43 g alcohol/kg body weight as mixed beverages together with food , and one control session when mineral water was substituted for the alcoholic beverages . In one of the alcohol sessions they received chlormethiazole , 1 g at bedtime and 0.5 g early the following morning , in the other , they were given placebo tablets . The following variables were studied : blood-alcohol concentration ; blood pressure ; heart rate ; blood lactate ; blood pyruvate ; urinary catecholamines ( only during hangover ) ; psychomotor and cognitive capacities ; as well as subjective reactions . During intoxication , heart rate and lactate-pyruvate ratio were significantly increased and performance efficiency was significantly deteriorated in comparison with the control condition . During hangover , heart rate , blood pressure , and lactate-pyruvate ratio were significantly elevated , and cognitive performance was still affected , in some tests to a significant degree . During this stage there was a great variation between subjects as regards . subjective hangover . Chlormethiazole was found to lower blood pressure and adrenaline output and , furthermore , to relieve unpleasant physical symptoms , but did not affect fatigue and drowsiness . The cognitive test results were only slightly infleenced by this agent , while psychomotor performance was significantly impaired . Subjects with severe subjective hangover seemed to benefit more from the chlormethiazole treatment than subjects with a mild hangover The aim of this study was to vali date a computer-assisted screening battery for classifying patients into two groups , those with and without cognitive impairment . Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a 1-year period . Patients meeting the study inclusion ary criteria ( N = 252 ) were administered the Neurobehavioral Evaluation System-3 ( NES3 ) computer-assisted battery . A detailed neuropsychological examination was carried out by an experienced neuropsychologist , who diagnosed the patient as cognitively impaired or not impaired . The neuropsychologist 's diagnosis was the gold st and ard . Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold st and ard . These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity in predicting diagnosis . Sensitivity and specificity for the least r and om classification procedure were 0.87 and 0.67 , respectively . The results suggest that computer-assisted screening methods are a promising means of triaging patients Performance on some complex and difficult tasks has been shown to be negatively affected for some time after an acute dose of alcohol has been cleared from the system . However , Dauncey reported impairment of a relatively simple reaction time task 3 hr after a dose of alcohol , when the blood alcohol concentration was at or near 0 . This impairment was positively related to the subject 's drinking history . A replication using the same task found a linear dose/impairment relationship during intoxication . A second simple reaction time task and a vigilance task showed a trend toward impairment , but only a divided attention task was significantly affected during intoxication . There was no significant effect of dose on any of these tests during a " morning after " session . The results are discussed in relation to the differences in method between Dauncey and this study Ethanol has been shown to have a relatively greater effect on error rates in speeded tasks than temazepam , and this may be due to a differential effect on the speed-accuracy trade-off ( SATO ) . This study used different instruction sets to influence the SATO . Forty-nine healthy volunteers ( 24 males , aged 18 - 41 years ) were allocated at r and om to one of three instruction conditions -- emphasising accuracy , neutral , and emphasising speed . After familiarisation , they took part in two sessions spaced at least 4 days apart in which they received either ethanol ( 0.8 g/kg , max 60 g males , 50 g females ) or placebo in r and omised order . Tests were administered starting at 30 and 75 min postdrug . Instructions significantly affected performance . In two maze tasks , one on paper , the other on a pen computer , the pattern of instruction effects was as expected . A significant increase in errors with ethanol was seen for both maze tasks , and there was a tendency to speed up with ethanol ( significant only for the pen computer task ) . Responses to fixed stimulus sequences on the Four-Choice Reaction Test also showed a tendency to speed up and an increase in errors with ethanol , while all other tests showed both slowing and increases in errors with ethanol compared to placebo . Error scores are consistently increased by ethanol in all test situations , while the effects of ethanol on speed are variable across tests AIMS To examine in as naturalistic a setting as possible whether having an alcohol-induced ' hangover ' impairs psychomotor and cognitive performance . PARTICIPANTS AND DESIGN The sample consisted of 71 male and female social drinkers who were tested twice , once at baseline and once after exposure to the study condition . They were r and omized into a control group who returned for testing on a prearranged date ( n = 33 ) , and a group who were instructed to make arrangements to return the day after a self-determined heavy drinking session ( n = 38 ) . Of the ' hangover ' group , 13 participants still had a blood alcohol concentration of > 1 mg/100 ml at the time of testing and these were analysed separately . All participants were students . MEASUREMENTS Psychomotor performance was assessed by means of a battery of psychomotor tasks , rate of information processing was tested by the Speed and Capacity of Language Processing Test ( SCOLP ) and subjective state was assessed by question naire measures . FINDINGS All participants in the ' hangover ' group reported subjective and physical symptoms of hangover on the second testing session . Performance was significantly impaired on the hits-key components of the vigilance task , was less accurate on the primary and secondary reaction time tasks and showed greater dispersion in range of ability for participants in the ' acute and hangover ' compared to ' control ' . Probe memory revealed no significant group effect . Ratings of subjective state revealed significant group differences for the variables ' ability to drive ' , ' concentrate ' and ' react quickly ' as well as ' tiredness ' . There were no group differences for performance on the SCOLP . CONCLUSION Hangover had negative effects on self-reported subjective and physical state and subtle effects on performance Twenty-one male managers who normally drink moderate amounts of alcohol participated in a placebo-controlled , double-blind , cross-over experiment . Subjects consumed either placebo or alcoholic drinks to attain a breath alcohol level of 0.10 during the evening before participation in Strategic Management Simulations . By the time of arrival at the simultaion laboratory on the following morning , breath alcohol levels were measured at 0.00 . Question naire responses indicated considerable hangover discomfort . Responses to semantic differential evaluative scales suggested that research participants evaluated their own managerial performance in the simulation setting as impaired . However , multiple ( vali date d ) measures of decision-making performance obtained in the simulation task did not show any deterioration of functioning . Previous research had shown considerable performance decrements in the same task setting , while blood/breath alcohol levels ranged from 0.05 through 0.10 % . Apparently , complex decision-making competence by persons who normally consume moderate amounts of alcohol may not be impaired by hangover caused by intoxication during the previous evening that remains at or below a blood alcohol level of 0.10 Background : This study examines the effect of alcohol intake on surgical dexterity immediately after and the morning after alcohol intake and minimal sleep deprivation by simulating a typical night out on the town AIMS Carry-over effects or the hangover hypothesis postulates that alcohol continues to impair performance the morning after drinking , even after low or moderate doses . Performance deficits have been attributed to the residual effects of recent drinking . The present study examined evidence for residual alcohol consumption on human performance when blood alcohol level has declined to zero . DESIGN A within-subjects , repeated measures , placebo controlled experiment was conducted with double-blind alcohol administration to investigate the effects of alcohol the morning after ingestion . SETTING All subjects were studied in Glasgow , Scotl and , UK . PARTICIPANTS Forty healthy male moderate to heavy social drinkers between 18 and 45 years of age . MEASUREMENTS Psychomotor performance , subjective state and quality of sleep were examined under alcohol and placebo with a 1-week interval between test sessions . Enough alcohol was given to place subjects above the legal limit for driving at peak blood alcohol . FINDINGS There was no evidence for impaired performance the morning after ingestion . Effects were found for subjective state and sleep quality . CONCLUSIONS The findings suggest that after a 100 mg/100 ml dose of alcohol people who : ( a ) have no alcohol left in their blood and ; ( b ) do not feel hung over will generally be fit to drive |
11,176 | 30,706,461 | There is insufficient evidence to guide continence care of adults in the rehabilitative phase after stroke .
More appropriately powered , multicentre trials of interventions are required to provide robust evidence for interventions to improve urinary incontinence after stroke | BACKGROUND Urinary incontinence can affect 40 % to 60 % of people admitted to hospital after a stroke , with 25 % still having problems when discharged from hospital and 15 % remaining incontinent after one year .
This is an up date of a review published in 2005 and up date d in 2008 .
OBJECTIVES To assess the effects of interventions for treating urinary incontinence after stroke in adults at least one-month post-stroke . | BACKGROUND AND PURPOSE To establish prevalence of urinary symptoms among community-dwelling stroke survivors and how these symptoms affected lives of these survivors compared with a nonstroke population . METHODS The present study was a community-based postal survey in Leicestershire community , UK ( that excluded institutional setting s ) , that was design ed to track stroke , urinary , and bowel symptoms and the effect of such symptoms on relationships , social life , daily activities , and overall quality of life . Subjects included 14 600 people who were living in the community and < /=40 years of age , r and omly selected from the Leicestershire Health Authority Register . RESULTS A 70 % response rate was achieved with the return of 10 226 question naires . Prevalence of reported stroke was 4 % ( n=423 ) . Prevalence of urinary symptoms was 34 % ( n=3197 ) . Overall , stroke survivors had a higher prevalence of symptoms than the nonstroke population ( 64 % to 32 % , respectively ) . These symptoms were reported to have more of an effect on the lives of the stroke survivors compared with the nonstroke population even when adjusted for age and sex differences . This reported impact was not related to the stroke per se but to the severity of the urinary symptoms . CONCLUSIONS These data show a high prevalence of urinary symptoms among community-dwelling stroke survivors . These symptoms were reported to have considerable impact on the lives of stroke survivors , which needs to be taken into account in future research and clinical practice Objective : To examine the effects of pelvic floor muscle training ( PFMT ) on the contractility of pelvic floor muscle and lower urinary tract symptoms in female stroke patients . Design : R and omized , single-blind controlled study . Setting : Outpatient rehabilitation hospital . Subjects : Thirty one female patients who were more than three months post-stroke and stress urinary incontinence . Interventions : The subjects were r and omized to either a PFMT group ( n = 16 ) , or a control group ( n = 15 ) . Both groups received general rehabilitation exercise for 6 weeks , but the PFMT group additionally received PFMT for 6 weeks . Main measures : Vaginal function test using a perineometer ( maximal vaginal squeeze pressure ) and intra-vaginal electromyography ( activity of pelvic floor muscle ) , and urinary symptoms and quality of life using a Bristol Female Lower Urinary Tract Symptom question naire . Results : After intervention , the maximal vaginal squeeze pressures for the PFMT and control groups were 18.35 ( 5.24 ) and 8.46 ( 3.50 ) mmHg , respectively . And the activities of pelvic floor muscle of the PFMT and control groups was 12.09 ( 2.24 ) ㎶ and 9.33 ( 3.40 ) ㎶ , respectively . After intervention , the changes of scores for inconvenience in the activity of daily living of the PFMT and control groups were −15.00 ( 6.25 ) and −0.17 ( 1.59 ) , respectively . In addition , the changes of score for lower urinary tract symptom was improved more in the PFMT group ( -4.17 ( 4.00 ) ) than in the control group ( -0.25 ( 1.29 ) ) ( P < 0.05 ) . Conclusions : These findings suggest that PFMT is beneficial for the management of urinary incontinence in female stroke patients BACKGROUND Lower urinary tract symptoms ( LUTS ) have a significant impact on quality of life ( QoL ) in post‑stroke patients . AIM The aim of this study was to evaluate the effect of pelvic floor muscle training ( PFMT ) on QoL parameters in men with post‑stroke LUTS . DESIGN R and omized , controlled and single‑blinded trial . SETTING Out patients , University Hospital . POPULATION Thirty‑one men , median age 68 ( interquartile range 60 - 74 ) years , with post‑stroke LUTS were included . Thirty participants completed the study . METHODS The participants r and omized to the treatment group were treated in a systematic , controlled and intensive PFMT program over 3 months ( 12 weekly sessions ) . The participants r and omized to the control group did not receive specific LUTS treatment . The effect was measured on the 36-Item Short Form Health Survey ( SF-36 ) and the Nocturia Quality ‑of‑Life ( N‑QoL ) Question naire . RESULTS The results on SF-36 indicated significant improvement within pre- and post‑test in the domains emotional role ( median 77 to 100 , P=0.03 ) and vitality ( median 65 to 70 , P=0.03 ) in the treatment group , but not the control group . There were no statistically significant differences between groups at pre‑test , post‑test or 6-month follow‑up . The results on N‑QoL indicated statistically significant differences between pre- and post‑test in the bother/concern domain in both groups and in sleep/energy for the control group , but not the treatment group . There were no statistically significant differences between groups . CONCLUSIONS PFMT may improve the emotional health and vitality domains of QoL in men with mild to moderate post‑stroke and LUTS ; however the improvements in the treatment group were not significantly better than for the control group . PFMT did not improve nocturia‑related QoL. CLINICAL REHABILITATION IMPACT This study is the first to evaluate the effect of PFMT on QoL parameters in men with mild to moderate post‑stroke and LUTS . The results indicate some short‑term effect on SF-36 but none on N‑QoL. However , further studies with larger sample sizes and with less restrictive inclusion and exclusion criteria are requested CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI ABSTRACT Purpose : To study the prevalence of depression at 12 months after stroke and to analyze factors associated with depression . Methods : This prospect i ve cross-sectional study was conducted among nine tertiary hospitals in Thail and . Stroke patients from the Thai Stroke Rehabilitation Registry who were admitted in inpatient rehabilitation wards were recruited for evaluation at the 12-month follow-up time point . Hospital Anxiety and Depression Scale ( HADS ) was used to evaluate depression in stroke . A score of ≥11 was considered as having depression . Univariate and multivariate analysis was used to investigate factors related with depression in stroke . Results : Two hundred stroke patients with a mean age of 62.1±12.5 years were recruited . Approximately 60 % were male . The number of stroke patients with depression at the 12-month follow-up was 42 ( 21.0 % , 95%CI 15.9%–27.2 % ) . Mean HADS score at 12-month follow-up was not significantly different from those at discharge . However , 28 ( 16.5 % ) stroke patients who did not have depression at discharge developed depression during the 12-month period . From multivariate analysis , complications and urinary incontinence were found to be significantly associated with depression after stroke with adjusted odds ratio of 3.65 ( 95%CI 1.11–12.06 ) and 4.82 ( 95%CI 1.74–13.38 ) , respectively . Conclusion : Depression is a common complication after stroke . This study found one-fifth of stroke survivors developed depression at the 12-month follow-up . Complications at discharge and urinary incontinence were significantly correlated with depression in multivariate analysis . Further study concerning interventions in decreasing depression should be performed in order to improve the quality of life of those stroke patients This pilot multicentered , r and omized , parallel , sham-controlled trial is intended to evaluate the effectiveness and safety of electroacupuncture therapy for poststroke patients with urinary incontinence . Forty stroke survivors aged > 19 years will be recruited in 2 hospitals in the Republic of Korea . Patients who experienced stroke within 2 years and satisfy criteria of urinary frequencies ≥2 with either 3 to 4 points on the Patient Perception of Intensity of Urgency Scale or 13 points or more on the Korean version of the International Prostate Symptom Scale ( K-IPSS ) will be identified , along with other eligibility criteria . Patients will be r and omly allocated to either a treatment or control group to receive 10 sessions of electroacupuncture or sham therapies , respectively . Patients and outcome assessors will be blinded . The primary outcome is the change of Total Urgency and Frequency Score between the baseline and the trial endpoint . The K-IPSS , the International Consultation on Incontinence Question naire for Urinary Incontinence Short Form , and the Lower Urinary Tract Symptoms Outcome Score will be evaluated for effectiveness assessment . Adverse events will be reported after every session . The Blinding Index will also be calculated . Data will be statistically analyzed with 0.05 significance levels by 2-sided testing 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 Background Urinary incontinence following acute stroke is common , affecting between 40%-60 % of people in hospital after a stroke . Despite the availability of clinical guidelines for urinary incontinence and urinary incontinence after stroke , national audit data suggest incontinence is often poorly managed . Conservative interventions ( e.g. bladder training , pelvic floor muscle training and prompted voiding ) have been shown to have some effect with participants in Cochrane systematic review s , but have not had their effectiveness demonstrated with stroke patients . Methods / Design A cluster r and omised controlled pilot trial design ed to assess the feasibility of a full-scale cluster r and omised trial and to provide preliminary evidence of the effectiveness and cost-effectiveness of a systematic voiding programme for the management of continence after stroke . Stroke services will be r and omised to receive the systematic voiding programme , the systematic voiding programme plus supported implementation , or usual care . The trial aims to recruit at least 780 participants in 12 stroke services ( 4 per arm ) . The primary outcome is presence/absence of incontinence at six weeks post-stroke . Secondary outcomes include frequency and severity of incontinence , quality of life and cost-utility . Outcomes will be measured at six weeks , three months and ( for participants recruited in the first three months ) twelve months after stroke . Process data will include rates of recruitment and retention and fidelity of intervention delivery . An integrated qualitative evaluation will be conducted in order to describe implementation and assist in explaining the potential mediators and modifiers of the process . Trial Registration IS RCT N : IS RCT Background This study protocol evaluates the effectiveness of adjuvant electroacupuncture ( EA ) for urinary retention in poststroke patients undergoing conventional treatments , in comparison with that of a sham control . Methods / design A multicenter , blinded , r and omized controlled trial will be conducted in three hospitals in the Republic of Korea . We are recruiting 54 stroke survivors ( aged > 19 years ) , who were diagnosed with urinary retention based on the results of two consecutive post-void residual ( PVR ) tests , and dividing them r and omly into two arms : the EA and Park-sham control groups . They will receive ten sessions of EA or sham treatment for 2 weeks . The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators . The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention . Then , the Korean version of the Qualiveen Question naire , the Korean version of the International Prostate Symptom Score , and the blinding index will be assessed . After each EA session or sham EA , adverse events will be reported to evaluate the safety of EA . Results will be analyzed by using the independent t-test or Mann-Whitney U test , based on both intention-to-treat and per- protocol principles . Discussion The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors . Trial Registration This study protocol was registered in Clinical Trials.gov ( NCT02472288 ) on 10 June 2015 The aim of this study was to examine the effects of acupuncture on urinary incontinence and to discuss why these acupoints were selected . Seven data bases were search ed for any r and omized controlled trials ( RCTs ) that investigated the use of acupuncture or acupressure as a treatment for urinary incontinence , and the Cochrane risk of bias tool was utilized to evaluate the risk of bias in each study . Four RCTs met all the inclusion criteria . The results from the selected RCTs failed to demonstrate any statistically significant improvements in urinary incontinence , although acupuncture or acupressure did exhibit favorable effects on overactive bladder symptoms and quality of life , in comparison with other conventional therapies . There have been limited results supporting acupuncture or acupressure as an effective treatment method for urinary incontinence ; therefore , further RCTs are required to confirm the effectiveness of acupuncture or acupressure in the treatment of urinary incontinence Introduction Ginger-salt-indirect moxibustion is widely applied to treat urge urinary incontinence after stroke , which is a common complication in stroke survivors . Moxa cone moxibustion and moxa box moxibustion are the main techniques of ginger-salt-indirect moxibustion . Our previous study had shown that ginger-salt-indirect moxibustion using moxa cones was feasible and effective for urination disorders post-stroke . This pilot study aims to assess the feasibility of conducting research to evaluate the efficacy and safety of ginger-salt-indirect moxibustion for patients with post-stroke urge urinary incontinence . Methods and analysis This is a multicentre , prospect i ve , single-blinded , pilot r and omised controlled trial . 120 eligible patients will be r and omly allocated to three groups . Treatment group A ( n=40 ) will receive moxa cone moxibustion and routine care ; treatment group B ( n=40 ) will receive moxa box moxibustion and routine care ; control group ( n=40 ) will only receive routine care for stroke recovery . The entire moxibustion treatment will consist of a total of 28 sessions during the course of 4 weeks . The primary outcome measure will be the increase in mean volume per void assessed at week 4 from the first moxibustion session ( baseline ) . Secondary outcome measures will include mean frequency of urination per day and quality of life assessment s measured by completion of the Incontinence Quality of Life Question naire and Barthel Index . All outcome measures will be assessed at baseline and at 4 and 16 weeks from baseline . Adverse events in the three groups will be recorded to assess the safety of moxibustion . Ethics and dissemination Research ethics was approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to the Capital Medical University ( ref : 2013BL-094 ) . Written informed consent will be obtained from all participants . Study results will be published in peer review ed journals . Trial registration number IS RCT N 44706974 AIMS The aim of this study was to evaluate the effect of Pelvic Floor Muscle Training ( PFMT ) in women with urinary incontinence ( UI ) after ischemic stroke . MATERIAL S AND METHODS Three hundred and thirty-nine medical records of stroke patients were search ed . Twenty-six subjects were r and omised to a Treatment Group ( 14 subjects ) or a Control Group ( 12 subjects ) in a single blinded , r and omised study . The intervention included 12 weeks of st and ardised PFMT . The outcome measures were : ( 1 ) diary recording the frequency of voiding , the number of incontinence episodes and used pads ; ( 2 ) 24-hr home pad test ; and ( 3 ) vaginal palpation of pelvic floor muscle evaluating function , strength , static and dynamic endurance . RESULTS Twenty-four subjects with urge , stress and mixed stress/urge incontinence , completed the study , 12 in each group . A significant improvement in frequency of voiding in daytime ( Treatment Group/Control Group : 7/8 at pre-test , 6/9 at post-test ( median values ) , P=0.018 ) , 24-hr pad test ( Treatment Group/Control Group : 8/12 to 2/8 g P=0.013 ) and dynamic endurance of pelvic floor muscle ( Treatment Group/Control Group : 11/20 to 20/8 contractions of Pelvic Floor Muscle , P=0.028 ) was demonstrated in the Treatment Group compared to the Control Group . A significant improvement in frequency of voiding in daytime ( decreased from seven to six , P=0.036 ) , pelvic floor muscle function ( P=0.034 ) , strength ( P=0.046 ) , static endurance increased from 9 to 30 sec ( P=0.028 ) and dynamic endurance increased from 11 to 20 contractions ( P=0.020 ) was also demonstrated within the Treatment Group , but not in the Control Group . CONCLUSION PFMT had a significant effect in women with UI after stroke measured by diaries , pad tests and vaginal palpation The aim of this study was to evaluate the long-lasting effect of pelvic floor muscle training ( PFMT ) in women with urinary incontinence after stroke measured by quality of life parameters . Twenty-four ( 24/24 ) women with urinary incontinence after stroke , who had completed a prospect i ve , r and omised controlled and single-blinded trial evaluating the effect of 12 weeks PFMT , were included in this follow-up study . The follow-up assessment s were done by telephone interview 6 months after the intervention . The effect was evaluated by The Short Form 36 ( SF-36 ) Health Survey Question naire and Incontinence Impact Question naire ( IIQ ) . Twenty-four subjects completed the study . In the treatment group , the SF-36 showed a trend to a long-lasting effect in one of the eight domains and the IIQ showed a tendency to decreased impact of UI in two sub-scales compared to the control group . Our data indicated that PFMT may have a long-lasting effect measured by quality of life parameters The aim of the current study was to evaluate the effect of pelvic floor muscle training in men with poststroke lower urinary tract symptoms . Thirty-one poststroke men , median age 68 years , were included in this single-blinded r and omized controlled trial . Thirty participants , 15 in each group , completed the study . The intervention consisted of 3 months ( 12 weekly sessions ) of pelvic floor muscle training in groups and home exercises . The effect was evaluated by the DAN-PSS-1 ( Danish Prostate Symptom Score ) question naire , a voiding diary , and digital anal palpation of the pelvic floor muscle . The DAN-PSS-1 , symptom score indicated a statistical significant improvement ( p < .01 ) in the treatment group from pretest to posttest , but not in the control group . The DAN-PSS-1 , total score improved statistically significantly in both groups from pretest to posttest ( treatment group : p < .01 ; control group : p = .03 ) . The median voiding frequency per 24 hours decreased from 11 at pretest to 7 ( 36 % ; p = .04 ) at posttest and to 8 ( 27 % ; p = .02 ) at follow-up in treatment group , although not statistical significantly more than the control group . The treatment group but not the control group improved statistically significantly in pelvic floor muscle function ( p < .01 ) and strength ( p < .01 ) from pretest to posttest and from pretest to follow-up ( p = .03 ; p < .01 ) . Compared with the control group the pretest to posttest was significantly better in the treatment group ( p = .03 ) . The results indicate that pelvic floor muscle training has an effect for lower urinary tract symptoms , although statistical significance was only seen for pelvic floor muscle Patients with acute hemispheric stroke and ensuring urinary incontinence were r and omly allocated to a ward using conventional methods of rehabilitation ( n = 13 ) or to a ward practicing rehabilitation governed by Functional Independence Measure ( FIM ) ( n = 21 ) . All patients were assessed on admission and on discharge using the Katz activities of daily living ( ADL ) index , the psychological general well-being index , item G of the FIM index ( FIM-G ) , and a mobility score . Patients admitted to the ward utilizing FIM were additionally evaluated using the total FIM on admission , repeatedly during the rehabilitation period and on discharge . An individual rehabilitation programme based on the latest FIM score was used throughout rehabilitation . There were no differences on admission between groups regarding clinical and demographic characteristics , ADL , mobility and mood . Twenty patients in the intervention group regained continence before discharge compared to 3 ( p < 0.01 ) in the control group . There was also a greater improvement in well-being in the intervention group compared to the control group ( p < 0.01 ) . This study has indicated that rehabilitation governed by the use of FIM reduced urinary incontinence and enhanced well-being better than conventional methods of rehabilitation . The results warrant a larger study to further investigate rehabilitation of incontinent stroke patients using FIM Study design : Double-blind , r and omised , multicentre study . Objectives : Efficacy and tolerability of propiverine extended-release ( ER ) compared with immediate-release ( IR ) were evaluated in patients with proven neurogenic detrusor overactivity ( NDO ) . Setting : Six Spinal Cord Injury Units located in Austria , Germany and Romania . Methods : Propiverine ER 45 mg s.i.d . or IR 15 mg t.i.d . were administered in patients with proven NDO . Outcomes were assessed at baseline ( V1 ) , and after 21 days of treatment ( V2 ) : Reflex volume served as primary , leak point volume and maximum detrusor pressure as secondary efficacy outcomes , treatment-related adverse events as tolerability outcomes . Results : Sixty-six patients with proven NDO were enrolled . Reflex volume ( ml ) increased significantly in the IR ( V1 : 100.9 , V2 : 202.9 ) and in the ER ( V1 : 89.8 , V2 : 180.3 ) group , no significant intergroup difference . Leak point volume increased , and maximum detrusor pressure decreased significantly in both groups , no significant intergroup differences . The percentage of patients presenting with incontinence was reduced by 14 % in the IR and by 39 % in the ER group , the difference is significant . Treatment-related adverse events manifested in 42 and 36 % following propiverine IR and ER , respectively . Conclusion : The urodynamic efficacy outcomes demonstrated both galenic formulations to be equieffective . However , following propiverine ER 45 mg s.i.d . higher continence rates compared with propiverine IR 15 mg t.i.d . were achieved , possibly indicative of more balanced plasma-levels . A slight tendency for superior tolerability outcomes of propiverine ER compared with IR was demonstrated . Sponsorship : The study was sponsored by an unrestricted educational grant of APOGEPHA Arzneimittel GmbH , Dresden , Germany This study was conducted to test the effectiveness of moxibustion therapy for patients with post-stroke urinary symptoms using International Prostate Symptom Score ( IPSS ) . Stroke patients with urinary symptoms were enrolled and assigned into the moxibustion group ( MO group ) and the control group by stratified r and omization . The MO group received moxibustion treatment on Zhong-Ji ( CV-3 ) , Guan-Yuan ( CV-4 ) and Qi-Hai ( CV-6 ) for 10 days , and the control group did not receive it . The effectiveness of urinary symptoms and activities of daily living were measured by IPSS and Barthel Index ( BI ) , respectively . These scales were examined by an independent blinded neurologist before treatment , and 10 days after therapy . Thirty nine subjects ( 20 in the MO group and 19 in the control group ) were included in the final analysis . The MO group showed more improvement on urinary symptoms than the control group . In conclusion , we suggest that moxibustion on Zhong-Ji ( CV-3 ) , Guan-Yuan ( CV-4 ) and Qi-Hai ( CV-6 ) is effective to post-stroke urinary symptoms Objective The objective of this study was to compare the effects of two frequencies of transcutaneous electrical nerve stimulation ( TENS ) on urinary incontinence caused by stroke . Methods Eighty-one patients with poststroke urinary incontinence were recruited and r and omized into the following three groups with a 1:1 ratio : a 20-Hz TENS group , a 75-Hz TENS group , and a no-treatment control group ( n = 27 per group ) . TENS currents were biphasic square waves with pulse duration s of 150 & mgr;secs and pulse frequencies of 20 Hz or 75 Hz and were applied for 30 mins once per day for 90 days . The positive electrodes were placed in the region of the second sacral level on opposite sides of the vertebral column ; the negative electrodes were placed on the inside of the middle and lower third of the junction between the posterior superior iliac spine and the ischial node . Overactive Bladder Symptom Scores , Barthel Index , urodynamic values , and voiding diary parameters were assessed before and after 90 days . Results The patients treated with 20 Hz had superior Overactive Bladder Symptom Scores , Barthel Index totals , urodynamic values , and voiding diary parameters ( P < 0.05 ) . In the 75-Hz group , values were statistically improved compared with the no-treatment group ( P < 0.05 ) , but the results were significantly inferior to those of the 20-Hz group ( P < 0.05 ) . Conclusions Twenty-hertz TENS improved incontinence symptoms and promoted activities of daily living better than 75-Hz TENS . These results will aid future research regarding TENS parameters Objective The aim of this study was to determine the effects of bladder reconditioning by indwelling urethral catheter ( IUC ) clamping before IUC removal in stroke patients . Design Sixty patients with stroke were r and omized to 0- , 1- , and 3-day IUC clamping groups . IUCs were removed without clamping in the 0-day group . In the other two groups , IUCs were clamped for 4 hrs followed by 5 mins of urinary drainage , a cycle repeated over 24 hrs in the 1-day and over 72 hrs in the 3-day clamping groups . Time to first voiding ( FV ) , first voided volume ( FV-vol ) , residual urine volume after FV , mean void volume , and residual urine volume on the third day after IUC removal were measured . We also recorded the voiding method such as self-voiding or intermittent catheterization , incidence of urinary tract infection , subjective complaints , and other complications . Results Time to FV , FV-vol , residual urine volume after FV , voiding method , mean voided volume , and residual urine volume on the third day after IUC removal had no significant difference among three groups , nor between the 0-day and the other two clamping groups . We observed a strong negative correlation between age and FV-vol . Of the patients in the 1- and 3-day clamping groups , 3 ( 7.5 % ) had symptomatic urinary tract infection and 9 ( 22.5 % ) complained of urinary leakage during IUC clamping program . Conclusions Bladder reconditioning through IUC clamping has no noticeable benefits in stroke patients and may induce additional problems . These findings suggest that IUC removal without clamping is superior to IUC clamping for bladder reconditioning in stroke patients Aims : To determine the effects of milnacipran hydrochloride , a serotonin-norepinephrine reuptake inhibitor ( SNRI ) , or paroxetine hydrochloride , a selective serotonin reuptake inhibitor , on overactive bladder ( OAB ) in neurologic diseases , given by objective measures of urodynamic studies . Methods : This is a prospect i ve open trial , and we enrolled 24 patients ( 16 men , 8 women ; mean age , 63.9 years ) with OAB in a neurology clinic . They were r and omly allocated into two groups : the milnacipran group ( 11 patients ) , and paroxetine group ( 13 patients ) . We started with 100 mg/day of milnacipran or 40 mg/day of paroxetine . Before and 3 months after the treatment , we performed a urinary question naire and urodynamic studies . Results : Milnacipran reduced daytime urinary frequency ( average , from 9.4 to 7.1 times , p < 0.001 ) , improved the quality of life index ( p = 0.023 ) , and increased bladder capacity ( average , from 289 to 377 ml , p = 0.009 ) as shown in urodynamic studies . No such changes were noted in the other categories of the lower urinary tract symptoms question naire or urodynamic studies , or in the paroxetine group . One male patient complained of mild voiding difficulty . Other adverse effects were not seen during the observation period . Conclusion : Milnacipran , an SNRI , increased bladder capacity as shown in urodynamic studies , and thereby ameliorated OAB in patients with neurologic diseases without serious adverse effects Objective : To evaluate the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS on the level of activities of daily living ( ADL ) of stroke patients . Setting : A university hospital . Patients : Patients who had had a stroke 30–240 days before entry to a university rehabilitation centre . Design : Controlled design with block r and omization and blinded assessment . Intervention : All patients had Todd – Davies exercises . In group 1 ( n = 30 ) TENS with frequency of 100 Hz was used at an intensity that the patient could tolerate ; in group 2 ( n = 30 ) patients were given placebo TENS . The treatment protocol consisted of 40 sessions ( eight weeks ) . Outcomes : The Barthel Index for daily living activities was used to measure functional changes over time , and the Ashworth Scale was used to measure spasticity in the elbow , knee and ankle . These measurements were made prior to and following the treatment by assessors unaware of the patient 's group allocation . Results : There were 30 patients in each group . Patients in group 1 ( active TENS ) were more disabled at entry to the study . Statistically significant improvements were recorded in all parameters such as feeding , transfer , hygiene , toileting , bathing , walking , climbing stairs , dressing , bowel and bladder care for group 1 ( p<0.001 ) but only in some items in group 2 . The change in total score was significant in both groups but the difference in the change score between the two groups was statistically significant ( p<0.001 ) . Spasticity was reduced in the active treatment group . Conclusion : TENS appears to be an effective adjunct in the regaining of motor functions and improving ADL in hemiplegic patients , but the accidental imbalance in severity of disability at entry makes interpretation uncertain OBJECTIVES To investigate the prevalence , incidence , clinical types , and prognostic effect of micturition disturbances in acute stroke . DESIGN Prospect i ve observational study . SETTING Geriatric department ( stroke and rehabilitation unit ) in a community hospital ( acute phase ) ; outpatient clinic , patients ' own homes , or nursing homes ( 3 months follow-up ) . PARTICIPANTS Three hundred fifteen patients ( mean age 77 ) with acute first-ever or recurrent stroke consecutively admitted to the hospital stroke unit . MEASUREMENTS Premorbid basic and instrumental activities of daily living ( ADLs ) and mental functioning ; comorbidity ; previous and actual micturition symptoms ; stroke syndromes ; medication use ; and poststroke mobility , ADLs , and cognition . RESULTS One hundred forty-seven patients ( 46 % ) had preexisting micturition disturbances ( urinary incontinence ( UI ) , n = 98 ; urgency/frequency , n = 37 ; voiding difficulties , n = 12 ) . Seventy-eight developed new symptoms ( UI , n = 65 ; urgency/frequency , n = 4 ; sustained retention , n = 9 ) . There were two UI types : urge UI ( n = 27 ) and UI with impaired awareness of bladder needs ( IA UI , n = 38 ) . In regression analyses , IA UI was the only micturition disturbance predicting mortality and need for nursing home care at 3 months ( odds ratio ( OR ) = 27.5 , 95 % confidence interval ( CI ) = 7.0 - 108.2 ) , together with poor mobility ( OR = 8.2 , 95 % CI = 2.6 - 26.2 ) , and partial or total anterior circulation stroke type ( OR = 3.6 , 95 % CI = 1.4 - 9.0 ) . CONCLUSION New-onset poststroke UI with impaired awareness of bladder needs is a strong and independent risk factor for poor outcome at 3 months . This probably reflects more serious brain damage , affecting sustained attention and information processing . Valid clinical tools to detect such dysfunction in stroke victims are needed . Clinical classification of poststroke UI is likely to improve management OBJECTIVE To probe the therapeutic effect and safety of ginger-salt-partitioned moxibustion on urination disorders poststroke . METHODS Eighty-two cases of cerebral apoplexy , including cerebral infa rct ion and cerebral hemorrhage , with urination disorders induced by neurogenic bladder at restoration stage were r and omly divided into a treatment group treated with ginger-salt-partitioned moxibustion at Shenque ( CV 8) and routine acupuncture , and a control group treated with routine acupuncture . Thirty-nine cases in the treatment group and 36 cases in the control group completed all treatments . The treatment was given 5 times each week and the therapeutic effects were observed after treatment of 3 consecutive weeks . RESULTS Ginger-salt-partitioned moxibustion in improvement of mean urination times of each day , mean times to be asked to awaken for the nursing personnel at night , mean times of urgent urinary incontinence at day for the patient , cases-times of urinary incontinence of the patient at night , and increasing degree of urinary incontinence was better than the control group ( P<0.01 , P<0.05 ) . CONCLUSION Ginger-salt-partitioned moxibustion is a safe and effective therapy for urination disorders poststroke OBJECTIVES To determine factors associated with recovery from poststroke urinary incontinence and to estimate the impact of this recovery on stroke outcome at 3 months . DESIGN Prospect i ve , observational study . SETTING Population -based stroke register . PARTICIPANTS Three hundred twenty-four incident cases of stroke with incontinence 1 week poststroke were identified from the register between January 1 , 1995 , and December 31 , 1998 . MEASUREMENTS At 3 months , 105 patients were dead and 12 were lost to follow-up . The remaining patients were classified by continence status ; those who had regained continence ( n = 127 ) were compared with those who remained incontinent ( n = 80 ) in terms of demographic details , stroke risk factors , premorbid disability , neurological impairments , and Oxfordshire Community Stroke Project stroke subtypes . Data at 3 months included disability using the modified Barthel Index ( BI ) ( without its urinary continence component ) and the Frenchay Activity Index ( FAI ) , and institutionalization . RESULTS Multivariate analysis showed being age 75 and older ( odds ratio ( OR ) = 0.38 ; 95 % confidence interval ( CI ) = 0.17 - 0.83 ) was associated with poor recovery from incontinence . Compared with subjects with total anterior circulatory infa rct ions , those with lacunar infa rct ions were more likely to regain continence ( OR = 3.66 ; 95 % CI = 1.10 - 12.2 ) , and compared with subjects with a BI between 0 and 14 , those with a BI between 15 and 18 were also more likely to regain continence ( OR = 21.8 ; 95 % CI = 5.95 - 79.7 ) . At 3 months , the incontinent group had greater institutionalization rates ( 27 ( 34 % ) vs 9 ( 7 % ) , P < .001 ) and worse disability , measured with BI and FAI ( BI : P < .001 , FAI : P = .002 ) . CONCLUSIONS Age 75 and older is independently associated with poor recovery from poststroke urinary incontinence . Further clinical trials are required to explore underlying mechanisms and efficacy of possible interventions for this group of stroke survivors . Recovery from poststroke urinary incontinence should be a major goal of stroke professionals because it is associated with lower institutionalization rates and less disability at 3 months The purpose of this study was to evaluate the effect of pelvic floor muscle training in women with urinary incontinence after ischemic stroke measured by quality of life ( QoL ) parameters . Three hundred thirty-nine medical records of stroke patients were search ed . Twenty-six subjects were r and omised to a Treatment Group or a Control Group in a single blinded , r and omised study design . The intervention included 12 weeks of st and ardised pelvic floor muscle training . The outcome was measured by the Short Form 36 ( SF-36 ) Health Survey Question naire and The Incontinence Impact Question naire ( IIQ ) . Twenty-four subjects completed the study . The SF-36 and IIQ did not show significant difference between the two groups . Despite the high prevalence of stroke with urinary incontinence , it is difficult to include these patients in such studies . The sample s were too small to detect any significant differences . Development of specific instruments for QoL in stroke patients with urinary incontinence can be recommended Objective The objective of this study was to examine the short-term effectiveness of prompted voiding ( PV ) in cognitively impaired homebound older adults . Design This was a prospect i ve , controlled exploratory study with a cross-over design where usual care controls crossed-over to the intervention following an 8-week observation period . Setting Adults aged 60 years and older with urinary incontinence and who met Center for Medicare and Medicaid Services criteria for being homebound were referred to the study by home care nurses from 2 large Medicare-approved home health agencies in a large metropolitan county in southwestern Pennsylvania . Nineteen cognitively impaired older adults were r and omly assigned to either the PV intervention or a usual care attention control group . Measures Measures used included structured continence and medical histories , Older American Research and Service Physical and Instrumental Activities of Daily Living scales , Folstein Mini Mental State Examination , Clock Drawing Test , Geriatric Depression Scale , Performance-Based Toileting Assessment , bladder diaries , and physical examination . Results Nineteen subjects were r and omly assigned to a PV ( n = 9 ) or delayed attention-control group ( n = 10 ) . Treatment subjects with complete pretreatment and posttreatment data ( n = 6 ) experienced a mean 60 % reduction in daytime incontinent episodes compared with a mean 37 % reduction among control subjects ( n = 10 ) . Following the control phase , subjects crossed over to the treatment protocol . A total of 15 subjects completed the PV protocol . Among all subjects completing the treatment protocol , there was a 22 % reduction in daytime incontinent episodes compared with true baseline ( immediately following the control phase for those crossing over from the control group ) . Conclusions The PV intervention result ed in clinical ly significant reductions in urinary incontinence for many of the participants , which may be achievable for many cognitively impaired homebound older adults OBJECTIVE To evaluate the clinical efficacy of electroacupuncture(EA ) for apoplectic urinary incontinence . METHODS Two hundred and four cases of apoplectic urinary incontinence were r and omized into an EA group ( 136 cases ) and an indwelling catheter group ( 68 cases ) . The EA was applied at Qugu ( CV 2 ) , Zhongji ( CV 3 ) , Shuidao ( ST 28 ) , Qihai ( CV 6 ) and Guanyuan ( CV 4 ) , etc . in the EA group,5 times a week . Indwelling catheter was applied in the indwelling catheter group at intervals of 2 - 4 hours , and periodic bladder irrigation along with bladder rehabilitation training were also given . The efficacies were evaluated after 4 weeks of treatment . Before and after treatment , the urination diary ( including the interval of urination , nocturia frequency , urination difficulty , urinary incontinence severity ) , bladder capacity , patients ' satisfaction of the two groups were observed and the efficacy was evaluated . RESULTS The total effective rate was 96.2 % ( 125/130 ) in the EA group , which was apparently superior to 87.5 % ( 56/64 ) in the indwelling catheter group ( P < 0.05 ) ; except for nocturia frequency in the indwelling catheter group , the total score and the subitem score in the urination diary were all improved significantly after treatment in both groups ( all P < 0.001 ) , which were more obvious in the EA group ( P < 0.001 , P < 0.05 ) ; the patients ' satisfaction and bladder capacity were all improved significantly after treatment in both groups ( all P < 0.001 ) , which were more obvious in the EA group ( both P < 0.001 ) . CONCLUSION The EA has an obvious effect for apoplectic urinary incontinence in urinary incontinence alleviation and bladder capacity increase , which has better efficacy than indwelling catheter therapy Abstract Objective : Resiniferatoxin ( RTX ) is an analogue of capsaicin with more than 1,000 times its potency in desensitizing C-fiber bladder afferent neurons . This study investigated the safety and efficacy of intravesical RTX in patients with refractory detrusor hyperreflexia ( DH ) . Methods : Thirty-six ( 22 males , 14 females ) neurologically impaired patients ( 20 spinal cord injury , 7 multiple sclerosis , 9 other neurologic diseases ) with urodynamically verified DH and intractable urinary symptoms despite previous anticholinergic drug use were treated prospect ively with intravesical RTX using dose escalation in a double-blind fashion at 4 centers . Patients received a single instillation of 100 ml of placebo ( n = 8 patients ) or 0.005 , 0.025 , 0.05 , 0.10 , 0.2 , 0.5 , or 1.0 fLM of RTX ( n = 4 each group ) . A visual analog pain scale ( VAPS ) ( 0 - 10 ; 10 = highest level of pain ) was used to quantify discomfort of application . Treatment effect was monitored using a bladder diary and cystometric bladder capacity at weeks 1 , 3 , 6 , and 1 2 posttreatment . Results : Mean VAPS scores revealed minimal to mild discomfort with values of 2.85 and 2.28 for the 0.5-j-LM and 1.0-j-LM RTX treatment groups , respectively . Due to the small sample size , there were no statistically significant changes in mean cystometric capacity ( MCC ) or incontinence episodes in each treatment dose group . However , at 3 weeks , MCC increased by 53 % and 48 % for the 0.5-j-μM and 1.0-j-μM RTX treatment groups , respectively . Patients in the 0.5-j-μM and 1.0-j-μM groups with MCC < 300 ml at baseline showed greater improvements in MCC at 120.5 % and 48 % , respectively . In some patients , MCC increased up to 500 % over baseline , despite a low RTX dose . Incontinence episodes decreased by 51.9 % and 52.7 % for the 0.5-j-LM and 1.0-j-LM RTX treatment groups , respectively . There were no long-term complications . Conclusion : Intravesical RTX administration , in general , is a well-tolerated new therapy for DH . This patient group was refractory to all previous oral pharmacologic therapy , yet some patients responded with significant improvement in bladder capacity and continence function shortly after RTX administration . Patients at risk for autonomic dysreflexia require careful monitoring during RTX therapy OBJECTIVES To examine the ( 1 ) short-term effectiveness of behavioral therapies in homebound older adults and ( 2 ) characteristics of responders and nonresponders to the therapies . DESIGN Prospect i ve , controlled clinical trial with cross-over design . SETTING Adults aged 60 and older with urinary incontinence and who met Health Care Financing Administration criteria for being homebound were referred to the study by homecare nurses from two large Medicare-approved home health agencies in a large metropolitan county in southwestern Pennsylvania . MEASURES Structured continence and medical history , OARS Physical and Instrumental Activities of Daily Living scales , Folstein Mini-Mental State Examination Score , Clock Drawing Test , Geriatric Depression Scale , Performance-Based Toileting Assessment , bladder diaries , and physical examination . RESULTS One hundred five subjects were r and omized to biofeedback-assisted pelvic floor muscle training ( 53 to the treatment group and 52 to the control groups ) . Control subjects with complete pre- and post-control data ( n = 45 ) experienced a median 6.4 % reduction in urinary accidents in contrast to a median 75.0 % reduction in subjects with complete pre- and post-treatment data ( n = 48 , P < .001 ) . Following the control phase , subjects crossed over to the treatment protocol . Eighty-five subjects completed treatment , achieving a median 73.9 % reduction in UI . Exercise adherence was the most consistent predictor of responsiveness to the behavioral therapy . CONCLUSIONS Clinical ly significant reductions in urinary incontinence are achievable with behavioral therapies in many cognitively intact homebound older adults despite high levels of co-morbidity and functional impairment OBJECTIVE To evaluate the effectiveness of electrical stimulation of the posterior tibialis nerve in men with neurogenic overactive bladder secondary to ischemic stroke at 45 days and 12 months after treatment . MATERIAL S AND METHODS We studied 24 patients older than 18 years , with ischemic stroke that occurred between 6 months and 3 years previously and with no prior urinary symptoms . These patients were r and omly allocated to receive electrical stimulation of the posterior tibialis nerve twice weekly for 6 weeks ( treatment group , n = 12 ) or general advice and stretching sessions 1 to 3 times monthly for 6 weeks ( control group , n = 12 ) . Each session lasted 30 minutes in both groups . The primary outcomes were reduction in urinary frequency , reduction in urinary urgency , and overall improvement in voiding diary variables . RESULTS Patients in the electrical stimulation group , in relation to baseline and to control group , experienced improvement in urinary symptoms , reducing urinary urgency and frequency , and reported subjective improvement after treatment . This effect persisted after 12 months of follow-up . The patients with lesion in right hemisphere , advanced age , and with higher body mass index presented more chance to develop urinary symptoms . CONCLUSION Electrical stimulation of the posterior tibialis nerve is a safe and effective option for the treatment of poststroke neurogenic overactive bladder in men , reducing urinary frequency and urgency |
11,177 | 31,193,651 | Large scale interventions delivered in both clinical and educational setting s appear to reduce self-harm and suicidal ideation post-intervention , and to a lesser extent at follow-up .
In community setting s , multi-faceted , place-based approaches seem to have an impact . | Background Young people require specific attention when it comes to suicide prevention , however efforts need to be based on robust evidence . | AIM The aim of the present study was to examine the intervention effects of intensive interpersonal psychotherapy for depressed adolescents with suicidal risk ( IPT-A-IN ) by comparison with treatment as usual ( TAU ) at schools . METHODS A total of 347 students from one-fifth of the classes of a high school in southern Taiwan completed the Beck Depression Inventory-II , the Beck Scale for Suicide Ideation , the Beck Anxiety Inventory and the Beck Hopelessness Scale for screening for suicidal risk . Of them , 73 depressed students who had suicidal risk on screening were r and omly assigned to the IPT-A-IN or TAU group . Analysis of covariance ( ANCOVA ) was performed to examine the effect of IPT-A-IN on reducing the severity of depression , suicidal ideation , anxiety and hopelessness . RESULTS Using the pre-intervention scores as covariates , the IPT-A-IN group had lower post-intervention severity of depression , suicidal ideation , anxiety and hopelessness than the TAU group . CONCLUSION Intensive school-based IPT-A-IN is effective in reducing the severity of depression , suicidal ideation , anxiety and hopelessness in depressed adolescents with suicidal risk IMPORTANCE In the United States , approximately 1 physician dies by suicide every day . Training physicians are at particularly high risk , with suicidal ideation increasing more than 4-fold during the first 3 months of internship year . Despite this increase , to our knowledge , very few efforts have been made to prevent the escalation of suicidal thoughts among training physicians . OBJECTIVE To assess the effectiveness of a web-based cognitive behavioral therapy ( wCBT ) program delivered prior to the start of internship year in the prevention of suicidal ideation in medical interns . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial conducted at 2 university hospitals with 199 interns from multiple specialties during academic years 2009 - 2010 or 2011 - 2012 . The current study was conducted from May 2009 to June 2010 and May 2011 to June 2012 , and data were analyzed using intent-to-treat principles , including last observation carried forward . INTERVENTIONS Interns were r and omly assigned to 2 study groups ( wCBT and attention-control group [ ACG ] ) , and completed study activities lasting 30 minutes each week for 4 weeks prior to starting internship year . Participants assigned to wCBT completed online CBT modules and those assigned to ACG received emails with general information about depression , suicidal thinking , and local mental health professionals . MAIN OUTCOMES AND MEASURES The Patient Health Question naire-9 was used to assess suicidal ideation ( ie , " thoughts that you would be better off dead or hurting yourself in some way " ) prior to the start of intern year and at 3-month intervals throughout the year . RESULTS A total of 62.2 % of interns ( 199 of 320 ) agreed to take part in the study ; 100 were assigned to the wCBT group and 99 to the ACG . During at least 1 point over the course of internship year , 12 % of interns ( 12 of 100 ) assigned to wCBT endorsed suicidal ideation compared with 21.2 % of interns ( 21 of 99 ) assigned to ACG . After adjusting for covariates identified a priori that have previously shown to increase the risk for suicidal ideation , interns assigned to wCBT were less likely to endorse suicidal ideation during internship year ( relative risk , 0.40 ; 95 % CI , 0.17- 0.91 ; P = .03 ) compared with those assigned to ACG . CONCLUSIONS AND RELEVANCE This study demonstrates that a free , easily accessible , brief wCBT program is associated with reduced likelihood of suicidal ideation among medical interns . Prevention programs with these characteristics could be easily disseminated to medical training programs across the country . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12610000628044 Background Suicide-related behaviours are common in young people and associated with a range of negative outcomes . There are few evidence -based interventions ; however , cognitive behavioural therapy ( CBT ) shows promise . Internet delivery of CBT is popular , with potential to increase reach and accessibility . Objective To test the effectiveness of an internet-based CBT program ( Reframe-IT ) in reducing suicide-related behaviours , depression , anxiety , hopelessness and improving problem solving and cognitive and behavioural skills in school students with suicide-related behaviours . Methods A parallel r and omised controlled trial testing the effectiveness of Reframe-IT plus treatment as usual ( TAU ) compared with TAU alone in reducing suicidal ideation , suicide attempts , depression , hopelessness , symptoms of anxiety , negative problem orientation and cognitive and behavioural skill acquisition was undertaken . We recruited students experiencing suicidal ideation from 18 schools in Melbourne , Australia , between August 2013 and December 2016 . The intervention comprised eight modules of CBT delivered online over 10 weeks with assessment s conducted at baseline , 10 weeks and 22 weeks . Findings Only 50 of the planned 169 participants were recruited . There were larger improvements in the Reframe-IT group compared with the TAU group for the primary outcome of suicidal ideation ( intervention −61.6 , SD 41.6 ; control −47.1 , SD 42.3 , from baseline to 22-week follow-up intervention ) ; however , differences were non-significant ( p=0.593 ) . There were no increases in distress in the majority of participants ( 91.1 % ) after completion of each module . Changes in depression and hopelessness partly mediated the effect of acquisition of CBT skills on suicidal ideation . Conclusions The trial was underpowered due to difficulties recruiting participants as a result of the complex recruitment procedures that were used to ensure safety of participants . Although there were no significant differences between groups , young people were safely and generally well engaged in Reframe-IT and experienced decreases in suicidal ideation and other symptoms as well as improvements in CBT skills . The study is the first online intervention trial internationally to include young people demonstrating all levels of suicide risk . Clinical implication s Integration of internet-delivered interventions for young people with suicide-related behaviour may result in reductions in these behaviours . Further research is needed , but research ers should feel more confident about being able to safely undertake research with young people who experience these behaviours . Trial registration number ACTRN12613000864729 The objective of this paper is to adapt attachment-based family therapy ( ABFT ) for use with suicidal lesbian , gay , and bisexual ( LGB ) adolescents and to obtain preliminary data on the feasibility and efficacy of the treatment with this population . In Phase I , a treatment development team modified ABFT to meet the unique needs of LGB suicidal youth . In Phase II , 10 suicidal LGB youth were offered 12 weeks of LGB sensitive ABFT . Adolescents ' report of suicidal ideation , depressive symptoms , and maternal attachment-related anxiety and avoidance were gathered at pretreatment , 6 weeks , and 12 weeks ( posttreatment ) . In Phase I , the treatment was adapted to : ( a ) include more individual time working with parents in order to process their disappointments , pain , anger , and fears related to their adolescent 's minority sexual orientation ; ( b ) address the meaning , implication s , and process of acceptance ; and ( c ) heighten parents ' awareness of subtle yet potent invalidating responses to their adolescents ' sexual orientation . Results of Phase II suggest this population can be recruited and successfully treated with a family based therapy , evidence d by high levels of treatment retention and significant decreases in suicidal ideation , depressive symptoms , and maternal attachment-related anxiety and avoidance . This is the first family-based treatment adapted and tested specifically for suicidal LGB adolescents . Though promising , the results are preliminary and more research on larger sample s is warranted Summary Background Self-harm in adolescents is common and repetition occurs in a high proportion of these cases . Scarce evidence exists for effectiveness of interventions to reduce self-harm . Methods This pragmatic , multicentre , r and omised , controlled trial of family therapy versus treatment as usual was done at 40 UK Child and Adolescent Mental Health Services ( CAMHS ) centres . We recruited young people aged 11–17 years who had self-harmed at least twice and presented to CAMHS after self-harm . Participants were r and omly assigned ( 1:1 ) to receive manualised family therapy delivered by trained and supervised family therapists or treatment as usual by local CAMHS . Participants and therapists were aware of treatment allocation ; research ers were masked . The primary outcome was hospital attendance for repetition of self-harm in the 18 months after group assignment . Primary and safety analyses were done in the intention-to-treat population . The trial is registered at the IS RCT N registry , number IS RCT N59793150 . Findings Between Nov 23 , 2009 , and Dec 31 , 2013 , 3554 young people were screened and 832 eligible young people consented to participation and were r and omly assigned to receive family therapy ( n=415 ) or treatment as usual ( n=417 ) . Primary outcome data were available for 795 ( 96 % ) participants . Numbers of hospital attendances for repeat self-harm events were not significantly different between the groups ( 118 [ 28 % ] in the family therapy group vs 103 [ 25 % ] in the treatment as usual group ; hazard ratio 1·14 [ 95 % CI 0·87–1·49 ] p=0·33 ) . Similar numbers of adverse events occurred in both groups ( 787 in the family therapy group vs 847 in the treatment as usual group ) . Interpretation For adolescents referred to CAMHS after self-harm , having self-harmed at least once before , our family therapy intervention conferred no benefits over treatment as usual in reducing subsequent hospital attendance for self-harm . Clinicians are therefore still unable to recommend a clear , evidence -based intervention to reduce repeated self-harm in adolescents . Funding National Institute for Health Research Health Technology Assessment programme OBJECTIVE Suicide is the third leading cause of death among adolescents . Many suicidal youths treated in emergency departments do not receive follow-up treatment as advocated by the National Strategy for Suicide Prevention . Two strategies for improving rates of follow-up treatment were compared . METHODS In a r and omized controlled trial , suicidal youths at two emergency departments ( N=181 ; ages ten to 18 ) were individually assigned between April 2003 and August 2005 to one of two conditions : an enhanced mental health intervention involving a family-based cognitive-behavioral therapy session design ed to increase motivation for follow-up treatment and safety , supplemented by care linkage telephone contacts after emergency department discharge , or usual emergency department care enhanced by provider education . Assessment s were conducted at baseline and approximately two months after discharge from the emergency department or hospital . The primary outcome measure was rates of outpatient mental health treatment after discharge . RESULTS Intervention patients were significantly more likely than usual care patients to attend outpatient treatment ( 92 % versus 76 % ; p=.004 ) . The intervention group also had significantly higher rates of psychotherapy ( 76 % versus 49 % ; p=.001 ) , combined psychotherapy and medication ( 58 % versus 37 % ; p=.003 ) , and psychotherapy visits ( mean 5.3 versus 3.1 ; p=.003 ) . Neither the emergency department intervention nor community outpatient treatment ( in exploratory analyses ) was significantly associated with improved clinical or functioning outcomes . CONCLUSIONS Results support efficacy of the enhanced emergency department intervention for improving linkage to outpatient mental health treatment but underscore the need for improved community outpatient treatment to prevent suicide , suicide attempts , and poor clinical and functioning outcomes for suicidal youths treated in emergency departments OBJECTIVE To determine whether brief intervention and contact is effective in reducing subsequent suicide mortality among suicide attempters in low and middle-income countries . METHODS Suicide attempters ( n = 1867 ) identified by medical staff in the emergency units of eight collaborating hospitals in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , China ) participated , from January 2002 to October 2005 , in a r and omized controlled trial to receive either treatment as usual , or treatment as usual plus brief intervention and contact ( BIC ) , which included patient education and follow-up . Overall , 91 % completed the study . The primary study outcome measurement was death from suicide at 18-month follow-up . FINDINGS Significantly fewer deaths from suicide occurred in the BIC than in the treatment-as-usual group ( 0.2 % versus 2.2 % , respectively ; chi2 = 13.83 , P < 0.001 ) . CONCLUSION This low-cost brief intervention may be an important part of suicide prevention programmes for underre source d low- and middle-income countries Background Suicide prevention organisations frequently use websites to educate the public , but evaluations of these websites are lacking . Aims To examine the effects of educative websites and the moderating effect of participant vulnerability . Method A total of 161 adults were r and omised to either view an educative website on suicide prevention or an unrelated website in a single-blinded r and omised controlled trial ( trial registration with the American Economic Association 's registry : RCT -ID : 000924 ) . The primary outcome was suicidal ideation ; secondary outcomes were mood , suicide-prevention-related knowledge and attitudes towards suicide/seeking professional help . Data were collected using question naires before ( T1 ) , immediately after exposure ( T2 ) , and 1 week after exposure ( T3 ) and analysed using linear mixed models . Results No significant intervention effect was identified for the entire intervention group with regard to suicidal ideation , but a significant and sustained increase in suicide-prevention-related knowledge ( T3vT1P < 0.001 , d = 1.12 , 95 % CI 0.96 to 1.28 ) and a non-sustained worsening of mood ( P < 0.001 , T2vT1 , d = -0.59 , -0.75 to -0.43 ) were observed . Participants with increased vulnerability experienced a partially sustained reduction of suicidal ideation ( T3vT1 , P < 0.001 , d = -0.34 , -0.50 to -0.19 ) . Conclusions Educative professional suicide prevention websites appeared to increase suicide-prevention-related knowledge , and among vulnerable individuals website exposure may be associated with a reduction of suicidal ideation The purpose of this study was to examine the efficacy of the Youth-Nominated Support Team-Version II ( YST-II ) for suicidal adolescents , an intervention based on social support and health behavior models , which was design ed to supplement st and ard treatments . Psychiatrically hospitalized and suicidal adolescents , 13 - 17 years of age , were r and omly assigned to treatment-as-usual ( TAU ) + YST-II ( n = 223 ) or TAU only ( n = 225 ) . YST-II provided tailored psychoeducation to youth-nominated adults in addition to weekly check-ins for 3 months following hospitalization . In turn , these adults had regular supportive contact with adolescents . Adolescents assigned to TAU + YST-II had an average of 3.43 ( SD = 0.83 ) nominated adults . Measures included the Suicidal Ideation Question naire-Junior ( SIQ-JR ; W. M. Reynolds , 1988 ) , Children 's Depression Rating Scale-Revised ( E. O. Poznanski & H. B. Mokros , 1996 ) , Beck Hopelessness Scale ( A. T. Beck & R. A. Steer , 1993 ) , and Child and Adolescent Functional Assessment Scale ( CAFAS ; K. Hodges , 1996 ) . YST-II had very limited positive effects , which were moderated by history of multiple suicide attempts , and no negative effects . It result ed in more rapid decreases in suicidal ideation ( SIQ-JR ) for multiple suicide attempters during the initial 6 weeks after hospitalization ( small-to-moderate effect size ) . For nonmultiple attempters , it was associated with greater declines in functional impairment ( CAFAS ) at 3 and 12 months ( small effect sizes ) . YST-II had no effects on suicide attempts and no enduring effects on SIQ-JR scores AIM Suicide attempt , ideation and deliberate self-harm are common among adolescents . Limited evidence exists regarding interventions that can reduce risk ; however , research indicates that maintaining contact with at-risk adults following discharge from services via letter or postcard can reduce risk . The aim of the study was to test a postcard intervention among people aged 15 - 24 who presented to mental health services but were not accepted , yet were at risk of suicide . METHODS A r and omized controlled trial of 3 years in duration was used . The intervention consisted of 12 postcards sent once a month for 12 months following presentation to the service . Key outcomes of interest were reduced rates of suicide attempt , suicidal ideation and deliberate self-harm , assessed at 12 and 18 months . RESULTS Participants reported that they liked receiving the postcard and that they used the strategies recommended . However , no significant effect of the postcard intervention was found on suicide risk , although participants in both groups improved on measures of mental health over the course of the study . CONCLUSIONS There remains a need for further research into youth-friendly interventions for young people at risk of suicide Objective To determine whether Therapeutic Assessment ( TA ) versus assessment as usual ( AAU ) improves engagement with follow-up in adolescents presenting with self-harm . Design R and omised controlled trial with 3 months naturalistic follow-up . Setting Child and adolescent mental health services in two London National Health Service Trusts . Participants 26 clinicians r and omised into TA and AAU groups recruited 70 newly referred adolescents with self-harm . Interventions TA , a manualised procedure including a basic psychosocial assessment and a 30 min therapeutic intervention ; AAU , st and ard psychosocial assessment . Main outcome measures Attendance at the first follow-up session ; number of the follow-up sessions attended and changes in Strengths and Difficulties Question naire and Children 's Global Assessment Scale scores . All measures were adjusted for clustering , social class , changes of therapist and previous contact with services . Results Using the data on all participants ( n=70 ) , those in the TA group were significantly more likely to attend the first follow-up appointment : 29 ( 83 % ) versus 17 ( 49 % ) , OR 5.12 , 95 % CI ( 1.49 to 17.55 ) and more likely to attend four or more treatment sessions : 14 ( 40 % ) versus 4 ( 11 % ) , OR 5.19 , 95 % CI ( 2.22 to 12.10 ) . Three months after the initial assessment there were no statistically significant differences between the groups on Strengths and Difficulties Question naire scores : 15.6 versus 16.0 , mean difference −0.37 , 95 % CI ( −3.28 to 2.53 ) or Children 's Global Assessment Scale scores : 64.6 versus 60.1 , mean difference 4.49 , 95 % CI ( −0.98 to 9.96 ) . Conclusions TA was associated with statistically significant improvement in engagement . TA could be usefully applied at the point of initial assessment for adolescents with self-harm . Trial registration IS RCT N 81605131 http://www.controlled-trials.com/IS RCT OBJECTIVE To compare group therapy with routine care in adolescents who had deliberately harmed themselves on at least two occasions within a year . METHOD Single-blind pilot study with two r and omized parallel groups that took place in Manchester , Engl and . Sixty-three adolescents aged 12 through 16 years were r and omly assigned to group therapy and routine care or routine care alone . Outcome data on suicide attempts were obtained without knowledge of treatment allocation on all r and omized cases ( 62/63 by direct interview ) on average 29 weeks later . The primary outcomes were depression and suicidal behavior . RESULTS In intention-to-treat analyses , adolescents who had group therapy were less likely to be " repeaters " at the end of the study ( i.e. , to have repeated deliberate self-harm on two or more further occasions ) than adolescents who had routine care ( 2/32 versus 10/31 ; odds ratio 6.3 ) , but the confidence intervals for this ratio were wide ( 95 % confidence interval 1.4 to 28.7 ) . They were also less likely to use routine care , had better school attendance , and had a lower rate of behavioral disorder than adolescents given routine care alone . The interventions did not differ , however , in their effects on depression or global outcome . CONCLUSIONS Group therapy shows promise as a treatment for adolescents who repeatedly harm themselves , but larger studies are required to assess more accurately the efficacy of this intervention BACKGROUND Suicidal behaviours in adolescents are a major public health problem and evidence -based prevention programmes are greatly needed . We aim ed to investigate the efficacy of school-based preventive interventions of suicidal behaviours . METHODS The Saving and Empowering Young Lives in Europe ( SEYLE ) study is a multicentre , cluster-r and omised controlled trial . The SEYLE sample consisted of 11,110 adolescent pupils , median age 15 years ( IQR 14 - 15 ) , recruited from 168 schools in ten European Union countries . We r and omly assigned the schools to one of three interventions or a control group . The interventions were : ( 1 ) Question , Persuade , and Refer ( QPR ) , a gatekeeper training module targeting teachers and other school personnel , ( 2 ) the Youth Aware of Mental Health Programme ( YAM ) targeting pupils , and ( 3 ) screening by professionals ( ProfScreen ) with referral of at-risk pupils . Each school was r and omly assigned by r and om number generator to participate in one intervention ( or control ) group only and was unaware of the interventions undertaken in the other three trial groups . The primary outcome measure was the number of suicide attempt(s ) made by 3 month and 12 month follow-up . Analysis included all pupils with data available at each timepoint , excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline . This study is registered with the German Clinical Trials Registry , number DRKS00000214 . FINDINGS Between Nov 1 , 2009 , and Dec 14 , 2010 , 168 schools ( 11,110 pupils ) were r and omly assigned to interventions ( 40 schools [ 2692 pupils ] to QPR , 45 [ 2721 ] YAM , 43 [ 2764 ] ProfScreen , and 40 [ 2933 ] control ) . No significant differences between intervention groups and the control group were recorded at the 3 month follow-up . At the 12 month follow-up , YAM was associated with a significant reduction of incident suicide attempts ( odds ratios [ OR ] 0·45 , 95 % CI 0·24 - 0·85 ; p=0·014 ) and severe suicidal ideation ( 0·50 , 0·27 - 0·92 ; p=0·025 ) , compared with the control group . 14 pupils ( 0·70 % ) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 ( 1·51 % ) in the control group , and 15 pupils ( 0·75 % ) reported incident severe suicidal ideation in the YAM group versus 31 ( 1·37 % ) in the control group . No participants completed suicide during the study period . INTERPRETATION YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents . These findings underline the benefit of this universal suicide preventive intervention in schools . FUNDING Coordination Theme 1 ( Health ) of the European Union Seventh Framework Programme This study replicated and extended previous evaluations of the Signs of Suicide ( SOS ) prevention program in a high school population using a more rigorous pre-test post-test r and omized control design than used in previous SOS evaluations in high schools ( Aseltine and DeMartino 2004 ; Aseltine et al. 2007 ) . SOS was presented to an ethnically diverse group of ninth grade students in technical high schools in Connecticut . After controlling for the pre-test reports of suicide behaviors , exposure to the SOS program was associated with significantly fewer self-reported suicide attempts in the 3 months following the program . Ninth grade students in the intervention group were approximately 64 % less likely to report a suicide attempt in the past 3 months compared with students in the control group . Similarly , exposure to the SOS program result ed in greater knowledge of depression and suicide and more favorable attitudes toward ( 1 ) intervening with friends who may be exhibiting signs of suicidal intent and ( 2 ) getting help for themselves if they were depressed or suicidal . In addition , high-risk SOS participants , defined as those with a lifetime history of suicide attempt , were significantly less likely to report planning a suicide in the 3 months following the program compared to lower-risk participants . Differential attrition is the most serious limitation of the study ; participants in the intervention group who reported a suicide attempt in the previous 3 months at baseline were more likely to be missing at post-test than their counterparts in the control group BACKGROUND Hospital-treated self-poisoning is common , with limited effective interventions for reducing subsequent suicidal behaviour . AIMS To test the efficacy of a postcard intervention to reduce suicidal behaviour . METHOD R and omised controlled trial of individuals who self-poisoned ( n = 2300 ) , the intervention consisted of nine postcards sent over 12 months versus usual treatment . Outcomes assessed at 12 months ( n = 2113 ) were suicidal ideation , suicide attempts and self-cutting ( proportion and event rates ) . RESULTS There was a significant reduction in any suicidal ideation ( relative risk reduction ( RRR ) = 0.31 , 95 % CI 0.22 - 0.38 ) , any suicide attempt ( RRR = 0.42 , 95 % CI 0.11 - 0.63 ) and number of attempts ( incidence rate ratios ( IRR ) = 0.64 , 95 % CI 0.42 - 0.97 ) . There was no significant reduction in any self-cutting ( RRR = 0.14 , 95 % CI -0.29 to 0.42 ) or self-cutting events ( IRR = 1.03 95 % CI 0.76 - 1.39 ) . CONCLUSIONS A postcard intervention reduced suicidal ideation and suicide attempts in a non-Western population . Sustained , brief contact by mail may reduce suicidal ideation and suicide attempts in individuals who self-poison OBJECTIVE To evaluate the feasibility of dialectical behavior therapy ( DBT ) implementation in a general child and adolescent psychiatric inpatient unit and to provide preliminary effectiveness data on DBT versus treatment as usual ( TAU ) . METHOD Sixty-two adolescents with suicide attempts or suicidal ideation were admitted to one of two psychiatric inpatient units . One unit used a DBT protocol and the other unit relied on TAU . Assessment s of depressive symptoms , suicidal ideation , hopelessness , parasuicidal behavior , hospitalizations , emergency room visits , and adherence to follow-up recommendations were conducted before and after treatment and at 1-year follow-up for both groups . In addition , behavioral incidents on the units were evaluated . RESULTS DBT significantly reduced behavioral incidents during admission when compared with TAU . Both groups demonstrated highly significant reductions in parasuicidal behavior , depressive symptoms , and suicidal ideation at 1 year . CONCLUSIONS DBT can be effectively implemented in acute-care child and adolescent psychiatric inpatient units . The promising results from this pilot study suggest that further evaluation of DBT for adolescent in patients appears warranted Objective To evaluate the effectiveness of a Cognitive-Behavioral therapy ( CBT ) for suicide prevention in decreasing suicidal ideation and hopelessness in a sample of depressed 12 to 18 year-old adolescents who had at least one previous suicidal attempt . Methods In a clinical trial , 30 depressed adolescents who attempted suicide in the recent 3 months were selected using simple sampling method and divided r and omly into intervention and wait-list control groups . Both groups received psychiatric interventions as routine . The intervention group received a 12 session ( once a week ) of CBT program according to the package developed by Stanley et al , including psychoeducational interventions and individual and family skills training modules . All of the patients were evaluated by Scale for Suicidal Ideation , Beck 's hopelessness Inventory , and Beck 's Depression Inventory before the intervention and after 12 weeks . Findings There were significant differences between the two groups regarding the scores of the above mentioned scales after 12 weeks . Fifty-four to 77 percent decreases in the mean scores of the used scales were observed in the invention group . There were no significant changes in the scores of the control wait-list group . The differences between pre- and post-intervention scores in the intervention group were significant . Conclusion CBT is an effective method in reducing suicidal ideation and hopelessness in the depressed adolescents with previous suicidal attempts Objective In current practice , treatment as usual ( TAU ) for suicidal adolescents includes evaluation , with little or no intervention provided in the emergency department ( ED ) , and disposition , usually to an inpatient psychiatry unit . The family-based crisis intervention ( FBCI ) is an emergency psychiatry intervention design ed to sufficiently stabilize suicidal adolescents within a single ED visit so that they may return home safely with their families . The objective of this article is to report efficacy outcomes related to FBCI for suicidal adolescents and their families . Methods A total of 142 suicidal adolescents ( age , 13–18 years ) and their families presenting for psychiatric evaluation to a large pediatric ED were r and omized to receive FBCI or TAU . Patients and caregivers completed self-report measures of suicidality , family empowerment , and satisfaction with care provided at pretest , posttest , and 3 follow-up time points over a 1-month period . Results Patients r and omized to FBCI were significantly more likely to be discharged home with outpatient follow-up care compared with their TAU counterparts ( P < 0.001 ) . Families r and omized to the FBCI condition reported significantly higher levels of family empowerment and client satisfaction with care at posttest compared with their TAU counterparts . Gains were maintained over the follow-up period . No completed suicides were reported during the study period in either condition . Conclusions Family-based crisis intervention is a model of care for suicidal adolescents that may be a viable alternative to traditional ED care that involves inpatient psychiatric hospitalization OBJECTIVE To establish whether an intervention given by child psychiatric social workers to the families of children and adolescents who had attempted suicide by taking an overdose reduced the patients ' suicidal feelings and improved family functioning . METHOD One hundred sixty-two patients , aged 16 or younger , who had deliberately poisoned themselves were r and omly allocated to routine care ( n = 77 ) or routine care plus the intervention ( n = 85 ) . The intervention consisted of an assessment session and four home visits by the social workers to conduct family problem-solving sessions . The control group received no visits . Both groups were assessed at the time of recruitment and 2 and 6 months later . The primary outcome measures were the Suicidal Ideation Question naire , the Hopelessness Scale , and the Family Assessment Device . RESULTS There were no significant differences in the primary outcomes between the intervention and control groups at either of the outcome assessment s. Parents in the intervention group were more satisfied with treatment ( mean difference 1.4 [ 95 % confidence interval 0.6 to 2.1 ] ) . A subgroup without major depression had much less suicidal ideation at both outcome assessment s ( analysis of covariance p < .01 ) compared with controls . CONCLUSIONS The home-based family intervention result ed in reduced suicidal ideation only for patients without major depression OBJECTIVE To evaluate whether Attachment-Based Family Therapy ( ABFT ) is more effective than Enhanced Usual Care ( EUC ) for reducing suicidal ideation and depressive symptoms in adolescents . METHOD This was a r and omized controlled trial of suicidal adolescents between the ages of 12 and 17 , identified in primary care and emergency departments . Of 341 adolescents screened , 66 ( 70 % African American ) entered the study for 3 months of treatment . Assessment occurred at baseline , 6 weeks , 12 weeks , and 24 weeks . ABFT consisted of individual and family meetings , and EUC consisted of a facilitated referral to other providers . All participants received weekly monitoring and access to a 24-hour crisis phone . Trajectory of change and clinical recovery were measured for suicidal ideation and depressive symptoms . RESULTS Using intent to treat , patients in ABFT demonstrated significantly greater rates of change on self-reported suicidal ideation at post-treatment evaluation , and benefits were maintained at follow-up , with a strong overall effect size ( ES = 0.97 ) . Between-group differences were similar on clinician ratings . Significantly more patients in ABFT met criteria for clinical recovery on suicidal ideation post-treatment ( 87 % ; 95 % confidence interval [ CI ] = 74.6 - 99.6 ) than patients in EUC ( 51.7 % ; 95 % CI = 32.4 - 54.32 ) . Benefits were maintained at follow-up ( ABFT , 70 % ; 95 % CI = 52.6 - 87.4 ; EUC 34.6 % ; 95 % CI = 15.6 - 54.2 ; odds ratio = 4.41 ) . Patterns of depressive symptoms over time were similar , as were results for a sub sample of adolescents with diagnosed depression . Retention in ABFT was higher than in EUC ( mean = 9.7 versus 2.9 ) . CONCLUSIONS ABFT is more efficacious than EUC in reducing suicidal ideation and depressive symptoms in adolescents . Additional research is warranted to confirm treatment efficacy and to test the proposed mechanism of change ( the Family Safety Net Study ) . Clinical Trial Registry Information : Preventing Youth Suicide in Primary Care : A Family Model , URL : http://www . clinical trials.gov , unique identifier : NCT00604097 The purpose of this article is to describe feasibility , safety , and outcome results from a treatment development trial of the SAFETY Program , a brief intervention design ed for integration with emergency services for suicide-attempting youths . Suicide-attempting youths , ages 11 to 18 , were enrolled in a 12-week trial of the SAFETY Program , a cognitive-behavioral family intervention design ed to increase safety and reduce suicide attempt ( SA ) risk ( N = 35 ) . Rooted in a social-ecological cognitive-behavioral model , treatment sessions included individual youth and parent session-components , with different therapists assigned to youths and parents , and family session-components to practice skills identified as critical in the pathway for preventing repeat SAs in individual youths . Outcomes were evaluated at baseline , 3-month , and 6-month follow-ups . At the 3-month posttreatment assessment , there were statistically significant improvements on measures of suicidal behavior , hopelessness , youth and parent depression , and youth social adjustment . There was one reported SA by 3 months and another by 6 months , yielding cumulative attempt rates of 3 % and 6 % at 3 and 6 months , respectively . Treatment satisfaction was high . Suicide-attempting youths are at high risk for repeat attempts and continuing mental health problems . Results support the value of a r and omized controlled trial to further evaluate the SAFETY intervention . Extension of treatment effects to parent depression and youth social adjustment are consistent with our strong family focus and social-ecological model of behavior change Background Suicide is a leading cause of death for children and youth in the United States . Although school based programs have been the principal vehicle for youth suicide prevention efforts for over two decades , few have been systematic ally evaluated . This study examined the effectiveness of the Signs of Suicide ( SOS ) prevention program in reducing suicidal behavior . Methods 4133 students in 9 high schools in Columbus , Georgia , western Massachusetts , and Hartford , Connecticut were r and omly assigned to intervention and control groups during the 2001–02 and 2002–03 school years . Self-administered question naires were completed by students in both groups approximately 3 months after program implementation . Results Significantly lower rates of suicide attempts and greater knowledge and more adaptive attitudes about depression and suicide were observed among students in the intervention group . Students ' race/ethnicity , grade , and gender did not alter the impact of the intervention on any of the outcomes assessed in this analysis . Conclusion This study has confirmed preliminary analysis of Year 1 data with a larger and more racially and socio-economically diverse sample . SOS continues to be the only universal school-based suicide prevention program to demonstrate significant effects of self-reported suicide attempts in a study utilizing a r and omized experimental design . Moreover , the beneficial effects of SOS were observed among high school-aged youth from diverse racial/ethnic background s , highlighting the program 's utility as a universal prevention program . Trial registration clinical trials.gov NCT000387855 OBJECTIVE To evaluate the efficacy of multisystemic therapy ( MST ) in reducing attempted suicide among predominantly African American youths referred for emergency psychiatric hospitalization . METHOD Youths presenting psychiatric emergencies were r and omly assigned to MST or hospitalization . Indices of attempted suicide , suicidal ideation , depressive affect , and parental control were assessed before treatment , at 4 months after recruitment , and at the 1-year posttreatment follow-up . RESULTS Based on youth report , MST was significantly more effective than emergency hospitalization at decreasing rates of attempted suicide at 1-year follow-up ; also , the rate of symptom reduction over time was greater for youths receiving MST . Also , treatment differences in patterns of change in attempted suicide ( caregiver report ) varied as a function of ethnicity , gender , and age . Moreover , treatment effects were found for caregiver-rated parental control but not for youth depressive affect , hopelessness , or suicidal ideation . CONCLUSIONS Results generally support MST 's effectiveness at reducing attempted suicide in psychiatrically disturbed youngsters , whereas the effects of hospitalization varied based on informant and youth demographic characteristics BACKGROUND Self-harm is a major risk factor for completed suicide . AIMS To determine the efficacy of a brief psychological intervention - culturally adapted manual-assisted problem-solving training ( C-MAP ) - delivered following an episode of self-harm compared with treatment as usual ( TAU ) . METHOD The study was a r and omised controlled assessor-masked clinical trial ( trial registration : Clinical Trials.gov NCT01308151 ) . All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi , Pakistan , were included in the study . A total of 250 patients were screened and 221 were r and omly allocated to C-MAP plus treatment as usual ( TAU ) or to TAU alone . All patients were assessed at baseline , at 3 months ( end of intervention ) and at 6 months after baseline . The primary outcome measure was reduction in suicidal ideation at 3 months . The secondary outcome measures included hopelessness , depression , coping re sources and healthcare utilisation . RESULTS A total of 108 patients were r and omised to the C-MAP group and 113 to the TAU group . Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory , which was sustained at 3 months after the completion of C-MAP . There was also a significant reduction in symptoms of depression compared with patients receiving TAU . CONCLUSIONS The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention Objective To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people . Design Two arm , single ( assessor ) blinded parallel r and omised allocation trial of a group therapy intervention in addition to routine care , compared with routine care alone . R and omisation was by minimisation controlling for baseline frequency of self harm , presence of conduct disorder , depressive disorder , and severity of psychosocial stress . Participants Adolescents aged 12 - 17 years with at least two past episodes of self harm within the previous 12 months . Exclusion criteria were : not speaking English , low weight anorexia nervosa , acute psychosis , substantial learning difficulties ( defined by need for specialist school ) , current containment in secure care . Setting Eight child and adolescent mental health services in the northwest UK . Interventions Manual based developmental group therapy programme specifically design ed for adolescents who harm themselves , with an acute phase over six weekly sessions followed by a booster phase of weekly groups as long as needed . Details of routine care were gathered from participating centres . Main outcome measures Primary outcome was frequency of subsequent repeated episodes of self harm . Secondary outcomes were severity of subsequent self harm , mood disorder , suicidal ideation , and global functioning . Total costs of health , social care , education , and criminal justice sector services , plus family related costs and productivity losses , were recorded . Results 183 adolescents were allocated to each arm ( total n=366 ) . Loss to follow-up was low ( < 4 % ) . On all outcomes the trial cohort as a whole showed significant improvement from baseline to follow-up . On the primary outcome of frequency of self harm , proportional odds ratio of group therapy versus routine care adjusting for relevant baseline variables was 0.99 ( 95 % confidence interval 0.68 to 1.44 , P=0.95 ) at 6 months and 0.88 ( 0.59 to 1.33 , P=0.52 ) at 1 year . For severity of subsequent self harm the equivalent odds ratios were 0.81 ( 0.54 to1.20 , P=0.29 ) at 6 months and 0.94 ( 0.63 to 1.40 , P=0.75 ) at 1 year . Total 1 year costs were higher in the group therapy arm ( £ 21 781 ) than for routine care ( £ 15 372 ) but the difference was not significant ( 95 % CI −1416 to 10782 , P=0.132 ) . Conclusions The addition of this targeted group therapy programme did not improve self harm outcomes for adolescents who repeatedly self harmed , nor was there evidence of cost effectiveness . The outcomes to end point for the cohort as a whole were better than current clinical expectations . Trial registration IS RCT N BACKGROUND Attempted suicide is a strong risk factor for subsequent suicidal behaviors . Innovative strategies to deal with people who have attempted suicide are needed , particularly in re source -poor setting s. AIMS To evaluate a brief educational intervention and periodic follow-up contacts ( BIC ) for suicide attempters in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , People 's Republic of China ) as part of the WHO Multisite Intervention Study on Suicidal Behaviors ( SUPRE-MISS ) . METHODS Among the 1,867 suicide attempters enrolled in the emergency departments of the participating sites , 922 ( 49.4 % ) were r and omly assigned to a brief intervention and contact ( BIC ) group and 945 ( 50.6 % ) to a treatment as usual ( TAU ) group . Repeated suicide attempts over the 18 months following the index attempt - the secondary outcome measure presented in this paper - were identified by follow-up calls or visits . Subsequent completed suicide - the primary outcome measure - has been reported in a previous paper . RESULTS Overall , the proportion of subjects with repeated suicide attempts was similar in the BIC and TAU groups ( 7.6 % vs. 7.5 % , chi(2 ) = 0.013 ; p = .909 ) , but there were differences in rates across the five sites . CONCLUSIONS This study from five low- and middle-income countries does not confirm the effectiveness of brief educational intervention and follow-up contacts for suicide attempters in reducing subsequent repetition of suicide attempts up to 18 months after discharge from emergency departments The present study evaluated the effectiveness of interpersonal problem-solving skills training ( IPSST ) for the treatment of self-poisoning patients . Thirty-nine self-poisoning patients were assigned r and omly either to IPSST or to a control treatment condition ( a brief problem-oriented approach ) . Both conditions were equally effective in reducing the number of presenting problems and in reducing hopelessness levels . However , the IPSST condition was significantly more effective than the control condition as determined by other outcome measures ( measures of interpersonal cognitive problem solving , self-rated personal problem-solving ability , perceived ability to cope with ongoing problems , and self-perception ) . Follow-up studies showed maintenance of IPSST treatment gains at 6 months and a greater reduction of repetition of self-poisoning in the IPSST group at 1 year posttreatment We describe initial pilot findings from a novel school-based approach to reduce youth depression and suicidality , the Empowering a Multimodal Pathway Towards Healthy Youth ( EMPATHY ) program . Here we present the findings from the pilot cohort of 3,244 youth aged 11–18 ( Grade s 6 - 12 ) . They were screened for depression , suicidality , anxiety , use of drugs , alcohol , or tobacco ( DAT ) , quality -of-life , and self-esteem . Additionally , all students in Grade s 7 and 8 ( mean ages 12.3 and 13.3 respectively ) also received an 8-session cognitive-behavioural therapy ( CBT ) based program design ed to increase resiliency to depression . Following screening there were rapid interventions for the 125 students ( 3.9 % ) who were identified as being actively suicidal , as well as for another 378 students ( 11.7 % ) who were felt to be at higher-risk of self-harm based on a combination of scores from all the scales . The intervention consisted of an interview with the student and their family followed by offering a guided internet-based CBT program . Results from the 2,790 students who completed scales at both baseline and 12-week follow-up showed significant decreases in depression and suicidality . Importantly , there was a marked decrease in the number of students who were actively suicidal ( from n=125 at baseline to n=30 at 12-weeks ) . Of the 503 students offered the CBT program 163 ( 32 % ) took part , and this group had significantly lower depression scores compared to those who did n’t take part . There were no improvements in self-esteem , quality -of-life , or the number of students using DAT . Only 60 students ( 2 % of total screened ) required external referral during the 24-weeks following study initiation . These results suggest that a multimodal school-based program may provide an effective and pragmatic approach to help reduce youth depression and suicidality . Further research is required to determine longer-term efficacy , reproducibility , and key program elements . Trial Registration Clinical Trials.gov OBJECTIVE To compare the efficacy of a skills-based treatment protocol to a supportive relationship therapy for adolescents after a suicide attempt . METHOD Thirty-nine adolescents ( 12 - 17 years old ) and parents who presented to a general pediatric emergency department or inpatient unit of a child psychiatric hospital after a suicide attempt were r and omized to either a skills-based or a supportive relationship treatment condition . Follow-up assessment s were conducted at intake and 3 and 6 months post-attempt . RESULTS In contrast to the low rates of treatment received by adolescent suicide attempters in the community , approximately 60 % of this sample completed the entire treatment protocol . Significant decreases in suicidal ideation and depressed mood at 3- and 6-month follow-ups were obtained , but there were no differences between treatment groups . There were six reattempts in the follow-up period . CONCLUSIONS When adolescents who attempt suicide are maintained in treatment , significant improvements in functioning can be realized for the majority of patients OBJECTIVE To determine whether a problem-solving intervention would increase adherence to outpatient treatment for adolescents after a suicide attempt . METHOD Sixty-three adolescents who had attempted suicide and were evaluated in an emergency department between 1997 and 2000 were r and omly assigned to undergo st and ard disposition planning or a compliance enhancement intervention using a problem-solving format . At 3 months after the intervention , all evaluable adolescents , guardians , and outpatient therapists were contacted to determine adherence to outpatient treatment . RESULTS At 3-month follow-up , the compliance enhancement group attended an average of 7.7 sessions compared with 6.4 sessions for the st and ard disposition group , but this difference was not statistically significant . However , after covarying barriers to receiving services in the community ( such as being placed on a waiting list and insurance coverage difficulties ) , the compliance enhancement group attended significantly more treatment sessions than the st and ard disposition-planning group ( mean = 8.4 versus 5.8 sessions ) . CONCLUSION Interventions design ed to improve treatment attendance must address not only individual and family factors but also service barriers encountered in the community that can impede access to services OBJECTIVE Suicide is a leading cause of death . New data indicate alarming increases in suicide death rates , yet no treatments with replicated efficacy or effectiveness exist for youths with self-harm presentations , a high-risk group for both fatal and nonfatal suicide attempts . We addressed this gap by evaluating Safe Alternatives for Teens and Youths ( SAFETY ) , a cognitive-behavioral , dialectical behavior therapy-informed family treatment design ed to promote safety . METHOD R and omized controlled trial for adolescents ( 12 - 18 years of age ) with recent ( past 3 months ) suicide attempts or other self-harm . Youth were r and omized either to SAFETY or to treatment as usual enhanced by parent education and support accessing community treatment ( E-TAU ) . Outcomes were evaluated at baseline , 3 months , or end of treatment period , and were followed up through 6 to 12 months . The primary outcome was youth-reported incident suicide attempts through the 3-month follow-up . RESULTS Survival analyses indicated a significantly higher probability of survival without a suicide attempt by the 3-month follow-up point among SAFETY youths ( cumulative estimated probability of survival without suicide attempt = 1.00 , st and ard error = 0 ) , compared to E-TAU youths ( cumulative estimated probability of survival without suicide attempt = 0.67 , st and ard error = 0.14 ; z = 2.45 , p = .02 , number needed to treat = 3 ) and for the overall survival curves ( Wilcoxon χ21 = 5.81 , p = .02 ) . Sensitivity analyses using parent report when youth report was unavailable and conservative assumptions regarding missing data yielded similar results for 3-month outcomes . CONCLUSION Results support the efficacy of SAFETY for preventing suicide attempts in adolescents presenting with recent self-harm . This is the second r and omized trial to demonstrate that treatment including cognitive-behavioral and family components can provide some protection from suicide attempt risk in these high-risk youths . Clinical trial registration information-Effectiveness of a Family-Based Intervention for Adolescent Suicide Attempters ( The SAFETY Study ) ; http:// clinical trials.gov/ ; NCT00692302 Background : Young people with early psychosis are at particularly high risk of suicide . However , there is evidence that early intervention can reduce this risk . Despite these advances , first episode psychosis patients attending these new services still remain at risk . To address this concern , a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre ( EPPIC ) . The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy ( LifeSPAN therapy ) for acutely suicidal patients with psychosis . We describe the development of these interventions in this paper . Method : Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC . Second , staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service . Third , a suicide risk monitoring system was introduced to identify those at highest risk . Finally , patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a r and omised controlled trial . Results : Fifty-six suicidal patients with first episode psychosis were r and omly assigned to st and ard clinical care or st and ard care plus LifeSPAN therapy . Forty-two patients completed the intervention . Clinical ratings and measures of suicidality and risk were assessed before , immediately after the intervention , and 6 months later . Benefits were noted in the treatment group on indirect measures of suicidality , e.g. , hopelessness . The treatment group showed a greater average improvement ( though not significant ) on a measure of suicide ideation . Conclusions : Early intervention in psychosis for young people reduces the risk of suicide . Augmenting early intervention with a suicide preventative therapy may further reduce this risk This study evaluated the effectiveness of a time-limited , outpatient intervention targeting suicidal young adults . Participants ( N = 264 ) were r and omly assigned to either the experimental treatment or the control condition ( i.e. , treatment as usual ) . In addition to intake assessment s , participants completed follow-ups at 1 , 6 , 12 , 18 , and 24 months . Both treatment and control participants evidence d significant improvement across all outcome measures throughout the follow-up period . Reductions were reported in suicidal ideation and behavior , associated symptomatology , and experienced stress , along with marked improvement in self-appraised problem-solving ability . Results also indicated that the experimental treatment was more effective than treatment as usual at retaining the highest risk participants . Available data demonstrate the efficacy of a time-limited , outpatient intervention for suicidal young adults . Implication s of current findings for intervention with and treatment of this population are discussed Young lesbian , gay , and bisexual ( young LGB ) individuals report higher rates of suicide ideation and attempts from their late teens through early twenties . Their high rate of Internet use suggests that online social networks offer a novel opportunity to reach them . This study explores online social networks as a venue for prevention research targeting young LGB . An automated data collection program was used to map the social connections between LGB self-identified individuals between 16 and 24 years old participating in an online social network . We then completed a descriptive analysis of the structural characteristics known to affect diffusion within such networks . Finally , we conducted Monte Carlo simulations of peer-driven diffusion of a hypothetical preventive intervention within the observed network under varying starting conditions . We mapped a network of 100,014 young LGB . The mean age was 20.4 years . The mean nodal degree was 137.5 , representing an exponential degree distribution ranging from 1 through 4309 . Monte Carlo simulations revealed that a peer-driven preventive intervention ultimately reached final sample sizes of up to 18,409 individuals . The network 's structure is consistent with other social networks in terms of the underlying degree distribution . Such networks are typically formed dynamically through a process of preferential attachment . This implies that some individuals could be more important to target to facilitate the diffusion of interventions . However , in terms of determining the success of an intervention targeting this population , our simulation results suggest that varying the number of peers that can be recruited is more important than increasing the number of r and omly-selected starting individuals . This has implication s for intervention design . Given the potential to access this previously isolated population , this novel approach represents a promising new frontier in suicide prevention and other research areas This research draws upon the interpersonal-psychological theory of suicide in the development of the LEAP intervention , a web-based selective preventive suicide intervention targeting cognitions of perceived burdensomeness toward others . The pilot r and omized controlled trial consisted of 80 adolescents ( 68.8 % female , 65.8 % Hispanic ) 13–19 of age years who were r and omly assigned to either the LEAP intervention or a psychoeducational control condition . Participants completed baseline , posttreatment , and 6-week follow-up assessment s. All participants reported high levels of satisfaction with the program . Findings on outcome variables differed across intent-to-treat analyses and treatment completer analyses . Intent-to-treat analysis yielded no significant between-condition differences in perceived burdensomeness at posttreatment or follow-up . Treatment completer analyses revealed significant between-condition differences on outcome variables such that participants who completed the LEAP intervention showed significantly lower perceived burdensomeness scores at postintervention and significantly lower perceived burdensomeness , thwarted belongingness , and depressive symptom scores at follow-up as compared to participants in the control condition . No significant differences in suicidal ideation were found between conditions . These findings support the promise of the LEAP intervention as a brief , web-based selective preventive intervention for reducing perceived burdensomeness among adolescents who complete the intervention . This study provides evidence that perceived burdensomeness can be modified via a psychosocial intervention . Future research is needed to identify ways to enhance adolescent engagement with and completion of the intervention We report a quasi-experimental investigation of an adaptation of Dialectical Behavior Therapy ( DBT ) with a group of suicidal adolescents with borderline personality features . The DBT group ( n = 29 ) received 12 weeks of twice weekly therapy consisting of individual therapy and a multifamily skills training group . The treatment as usual ( TAU ) group ( n = 82 ) received 12 weeks of twice weekly supportive-psychodynamic individual therapy plus weekly family therapy . Despite more severe pre-treatment symptomatology in the DBT group , at post-treatment this group had significantly fewer psychiatric hospitalizations during treatment , and a significantly higher rate of treatment completion than the TAU group . There were no significant differences in the number of suicide attempts made during treatment . Examining pre-post change within the DBT group , there were significant reductions in suicidal ideation , general psychiatric symptoms , and symptoms of borderline personality . DBT appears to be a promising treatment for suicidal adolescents with borderline personality characteristics To assess whether writing with cognitive change or exposure instructions reduces depression or suicidality , 121 undergraduates screened for suicidality wrote for 20 minutes on 4 days over 2 weeks . They were r and omly assigned to reinterpret or to write and rewrite traumatic events/emotions , or to write about innocuous topics . The three groups ( N = 98 ) who completed pre- , post- , and 6-week follow-up were not different on suicidality or depression . All subjects reported fewer automatic negative thoughts over the 2 weeks ; they also reported higher self-regard but more health center visits at follow-up . Suicidal thoughts may be more resistant than physical health to writing interventions Little evidence exists regarding the efficacy of suicide prevention programmes among the youth . This pilot study aim ed to test the effects of a specifically design ed , eight‐module Internet‐based programme on suicidal ideation among secondary school students Objective : Deliberate self-harm ( DSH ) , general hospital admission and psychiatric hospital admission are common in women meeting criteria for borderline personality disorder ( BPD ) . Dialectical behaviour therapy ( DBT ) has been reported to be effective in reducing DSH and hospitalization . Method : A r and omized controlled trial of 73 female subjects meeting criteria for BPD was carried out with intention-to-treat analyses and per- protocol analyses . The intervention was DBT and the control condition was treatment as usual plus waiting list for DBT ( TAU+WL ) , with outcomes measured after 6 months . Primary outcomes were differences in proportions and event rates of : any DSH ; general hospital admission for DSH and any psychiatric admission ; and mean difference in length of stay for any hospitalization . Secondary outcomes were disability and quality of life measures . Results : Both groups showed a reduction in DSH and hospitalizations , but there were no significant differences in DSH , hospital admissions or length of stay in hospital between groups . Disability ( days spent in bed ) and quality of life ( Physical , Psychological and Environmental domains ) were significantly improved for the DBT group . Conclusion : DBT produced non-significant reductions in DSH and hospitalization when compared to the TAU+WL control , due in part to the lower than expected rates of hospitalization in the control condition . Nevertheless , DBT showed significant benefits for the secondary outcomes of improved disability and quality of life scores , a clinical ly useful result that is also in keeping with the theoretical constructs of the benefits of DBT OBJECTIVE The purpose of this study was to conduct a treatment development study to examine the feasibility , acceptability , and preliminary efficacy of treating depressed , suicidal adolescents and their depressed parent concurrently in a cognitive behavioral therapy ( CBT ) protocol ( Parent-Adolescent-CBT [ PA-CBT ] ) . METHODS A r and omized , controlled , repeated measures design was used to test the hypothesis that PA-CBT would lead to greater reductions in suicidality and depression compared with Adolescent Only CBT ( AO-CBT ) . Participants included 24 adolescent and parent dyads in which the adolescent met American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) criteria for current major depressive episode ( MDE ) and the parent met DSM-IV criteria for current or past MDE . RESULTS The concurrent protocol was found to be feasible to implement with most depressed adolescents and parents . Adolescent ratings of program satisfaction were somewhat lower in PA-CBT , suggesting that some teens view treatment negatively when they are required to participate with a parent . The concurrent treatment protocol was more effective in reducing depressed mood in the parent-adolescent dyad at the end of maintenance treatment ( 24 weeks ) than treating an adolescent alone for depression ; the largest effect was on parental depressed mood . This difference between dyads was no longer significant , however , at the 48 week follow-up . Adolescent and parent suicidal ideation improved equally in both groups during active and maintenance treatment , and remained low at follow-up in both groups . CONCLUSIONS The PA-CBT protocol is feasible to conduct and acceptable to most but not all adolescents . The strongest effect was on parental depressed mood . A larger study that has sufficient power to test efficacy and moderators of treatment outcome is necessary to better underst and which adolescents would benefit most from concurrent treatment with a parent OBJECTIVE Family processes are a risk factor for suicide but few studies target this domain . We evaluated the effectiveness of a family intervention , the Re source ful Adolescent Parent Program ( RAP-P ) in reducing adolescent suicidal behavior and associated psychiatric symptoms . METHOD A preliminary r and omized controlled trial compared RAP-P plus Routine Care ( RC ) to RC only , in an outpatient psychiatric clinic for N = 48 suicidal adolescents and their parents . Key outcome measures of adolescent suicidality , psychiatric disability , and family functioning were completed at pre-treatment , 3-month , and 6-month follow-up . RESULTS RAP-P was associated with high recruitment and retention , greater improvement in family functioning , and greater reductions in adolescents ' suicidal behavior and psychiatric disability , compared to RC alone . Benefits were maintained at follow-up with a strong overall effect size . Changes in adolescent 's suicidality were largely mediated by changes in family functioning . CONCLUSION The study provides preliminary evidence for the use of family-focused treatments for adolescent suicidal behavior in outpatient setting s. Clinical trial registration information-Family intervention for adolescents with suicidal behaviour : A r and omized controlled trial and mediation analysis ; http://anzctr.org/ ; ACTRN12613000668707 Background An earlier r and omised controlled trial demonstrated improved treatment engagement in adolescents who received Therapeutic Assessment ( TA ) versus Assessment As Usual ( AAU ) , following an emergency presentation with self-harm . Objectives To determine 2-year outcomes for the same adolescents focusing on frequency of Accident and Emergency ( A&E ) self-harm presentations and treatment engagement . Method Patients in the TA groups ( n=35 ) and the AAU group ( n=34 ) were followed up 2 years after the initial assessment . Their primary and secondary care electronic records were analysed . Results There was no significant difference in the frequency of self-harm result ing in A&E presentations between the two groups ( OR 0.69 , 95 % CI 0.23 to 2.13 , p=0.53 ) . Treatment engagement remained higher in the TA group than the AAU group . Conclusions TA is not associated with a lower frequency of A&E self-harm presentations . The effect of TA on engagement is maintained 2 years after the initial assessment . Interventions to reduce self-harm in adolescents are needed . Trial registration IS RCT N 81605131 , http://www.controlled-trials.com/IS RCT This study tested the efficacy of a school-based prevention program for reducing suicide potential among high-risk youth . A sample of 105 youth at suicide risk participated in a three-group , repeated- measures , intervention study . Participants in ( 1 ) an assessment plus 1-semester experimental program , ( 2 ) an assessment plus 2-semester experimental program , and ( 3 ) an assessment -only group were compared , using data from preintervention , 5-month , and 10-month follow-up assessment s. All groups showed decreased suicide risk behaviors , depression , hopelessness , stress , and anger ; all groups also reported increased self-esteem and network social support . Increased personal control was observed only in the experimental groups , and not in the assessment -only control group . The potential efficacy of the experimental school-based prevention program was demonstrated . The necessary and sufficient strategies for suicide prevention , however , need further study as the assessment -only group , who received limited prevention elements , showed improvements similar to those of the experimental groups OBJECTIVE To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial . METHOD Adolescents who had made a recent suicide attempt and had unipolar depression ( n = 124 ) were either r and omized ( n = 22 ) or given a choice ( n = 102 ) among three conditions . Two participants withdrew before treatment assignment . The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents ( n = 17 ) , a medication algorithm ( n = 14 ) , or the combination ( n = 93 ) . The participants were followed up 6 months after intake with respect to rate , timing , and predictors of a suicidal event ( attempt or acute suicidal ideation necessitating emergency referral ) . RESULTS The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12 , respectively , with a median time to event of 44 days . Higher self-rated depression , suicidal ideation , family income , greater number of previous suicide attempts , lower maximum lethality of previous attempt , history of sexual abuse , and lower family cohesion predicted the occurrence , and earlier time to event , with similar findings for the outcome of attempts . A slower decline in suicidal ideation was associated with the occurrence of a suicidal event . CONCLUSIONS In this open trial , the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable sample s , suggesting that this intervention should be studied further . Important treatment targets include suicidal ideation , family cohesion , and sequelae of previous abuse . Because 40 % of events occurred with 4 weeks of intake , an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted OBJECTIVE College counseling centers ( CCCs ) are increasingly being called upon to treat highly distressed students with complex clinical presentations . This study compared the effectiveness of Dialectical Behavior Therapy ( DBT ) for suicidal college students with an optimized control condition and analyzed baseline global functioning as a moderator . METHOD The intent-to-treat ( ITT ) sample included 63 college students between the ages of 18 and 25 years who were suicidal at baseline , reported at least 1 lifetime nonsuicidal self-injurious ( NSSI ) act or suicide attempt , and met 3 or more borderline personality disorder ( BPD ) diagnostic criteria . Participants were r and omly assigned to DBT ( n = 31 ) or an optimized treatment-as-usual ( O-TAU ) control condition ( n = 32 ) . Treatment was provided by trainees , supervised by experts in both treatments . Both treatments lasted 7 - 12 months and included both individual and group components . Assessment s were conducted at pretreatment , 3 months , 6 months , 9 months , 12 months , and 18 months ( follow-up ) . RESULTS Mixed effects analyses ( ITT sample ) revealed that DBT , compared with the control condition , showed significantly greater decreases in suicidality , depression , number of NSSI events ( if participant had self-injured ) , BPD criteria , and psychotropic medication use and significantly greater improvements in social adjustment . Most of these treatment effects were observed at follow-up . No treatment differences were found for treatment dropout . Moderation analyses showed that DBT was particularly effective for suicidal students who were lower functioning at pretreatment . CONCLUSIONS DBT is an effective treatment for suicidal , multiproblem college students . Future research should examine the implementation of DBT in CCCs in a stepped care approach OBJECTIVE We examined whether mentalization-based treatment for adolescents ( MBT-A ) is more effective than treatment as usual ( TAU ) for adolescents who self-harm . METHOD A total of 80 adolescents ( 85 % female ) consecutively presenting to mental health services with self-harm and comorbid depression were r and omly allocated to either MBT-A or TAU . Adolescents were assessed for self-harm , risk-taking and mood at baseline and at 3-monthly intervals until 12 months . Their attachment style , mentalization ability and borderline personality disorder ( BPD ) features were also assessed at baseline and at the end of the 12-month treatment . RESULTS MBT-A was more effective than TAU in reducing self-harm and depression . This superiority was explained by improved mentalization and reduced attachment avoidance and reflected improvement in emergent BPD symptoms and traits . CONCLUSIONS MBT-A may be an effective intervention to reduce self-harm in adolescents PROBLEM Few empirically tested , school-based , suicide-prevention programs exist . The purpose of this study was to evaluate the postintervention efficacy of Counselors-CARE ( C-CAST ) and Coping and Support Training ( CAST ) vs. " usual care " controls for reducing suicide risk . METHODS A r and omized prevention trial ; 341 potential dropouts , 14 to 19 years old , from seven high schools ( 52 % female , 56 % minorities ) participated . Trend analyses using data from three time points assessed over time changes . FINDINGS Significant decreases occurred for all youth in suicide-risk behaviors , depression , and drug involvement . Intervention-specific effects occurred for decreases in depression . CONCLUSIONS School-based prevention approaches are feasible and show promise for reducing suicidal behaviors and related depression In this study , the authors investigated the efficacy of the Youth-Nominated Support Team-Version 1 ( YST-1 ) , a psychoeducational social network intervention , with 289 suicidal , psychiatrically hospitalized adolescents ( 197 girls , 92 boys ) . Adolescents were r and omly assigned to treatment-as-usual plus YST-1 or treatment-as-usual only . Assessment s were completed pre- and postintervention ( 6 months ) . There were no main effects for YST-1 on suicide ideation or attempts , internalizing symptoms , or related functional impairment . Relative to other girls , however , those who received YST-1 reported greater decreases in self-reported suicidal ideation ( actually treated analytic strategy ) and significantly greater decreases in mood-related functional impairment reported by their parents ( intent to treat and actually treated analytic strategies ) . This is the first r and omized controlled clinical trial to investigate the efficacy of a social network intervention with suicidal youths Three-hundred ninety-three adolescents from six schools participated in a study aim ed at examining the effectiveness of an experiential suicide prevention program with regard to suicidal tendencies , hopelessness , ego identity , and coping ability . The subjects were r and omly divided into experimental ( n = 215 ) and control ( n = 178 ) groups . The experimental groups took part in seven weekly 2-hour meetings . The program was based on the notion that a gradual , controlled confrontation and exploration of inner experiences and life difficulties related to suicidal behavior accompanied by an emphasis on coping strategies can immunize against self-destructive feelings . In this pretest-posttest design , the students completed question naires of suicidal tendencies , hopelessness , ego identity , and coping ability before and after the program . The statistical analyses showed that the experimental groups were superior to the controls , with at least some of the dependent measures pointing out the effectiveness of the program Importance Suicide is a leading cause of death among 10- to 24-year-old individuals in the United States ; evidence on effective treatment for adolescents who engage in suicidal and self-harm behaviors is limited . Objective To evaluate the efficacy of dialectical behavior therapy ( DBT ) compared with individual and group supportive therapy ( IGST ) for reducing suicide attempts , nonsuicidal self-injury , and overall self-harm among high-risk youths . Design , Setting , and Participants This r and omized clinical trial was conducted from January 1 , 2012 , through August 31 , 2014 , at 4 academic medical centers . A total of 173 participants ( pool of 195 ; 22 withdrew or were excluded ) 12 to 18 years of age with a prior lifetime suicide attempt ( ≥3 prior self-harm episodes , suicidal ideation , or emotional dysregulation ) were studied . Adaptive r and omization balanced participants across conditions within sites based on age , number of prior suicide attempts , and psychotropic medication use . Participants were followed up for 1 year . Interventions Study participants were r and omly assigned to DBT or IGST . Treatment duration was 6 months . Both groups had weekly individual and group psychotherapy , therapist consultation meetings , and parent contact as needed . Main Outcomes and Measures A priori planned outcomes were suicide attempts , nonsuicidal self-injury , and total self-harm assessed using the Suicide Attempt Self-Injury Interview . Results A total of 173 adolescents ( 163 [ 94.8 % ] female and 97 [ 56.4 % ] white ; mean [ SD ] age , 14.89 [ 1.47 ] years ) were studied . Significant advantages were found for DBT on all primary outcomes after treatment : suicide attempts ( 65 [ 90.3 % ] of 72 receiving DBT vs 51 [ 78.9 % ] of 65 receiving IGST with no suicide attempts ; odds ratio [ OR ] , 0.30 ; 95 % CI , 0.10 - 0.91 ) , nonsuicidal self-injury ( 41 [ 56.9 % ] of 72 receiving DBT vs 26 [ 40.0 % ] of 65 receiving IGST with no self-injury ; OR , 0.32 ; 95 % CI , 0.13 - 0.70 ) , and self-harm ( 39 [ 54.2 % ] of 72 receiving DBT vs 24 [ 36.9 % ] of 65 receiving IGST with no self-harm ; OR , 0.33 ; 95 % CI , 0.14 - 0.78 ) . Rates of self-harm decreased through 1-year follow-up . The advantage of DBT decreased , with no statistically significant between-group differences from 6 to 12 months ( OR , 0.65 ; 95 % CI , 0.12 - 3.36 ; P = .61 ) . Treatment completion rates were higher for DBT ( 75.6 % ) than for IGST ( 55.2 % ) , but pattern-mixture models indicated that this difference did not informatively affect outcomes . Conclusions and Relevance The results of this trial support the efficacy of DBT for reducing self-harm and suicide attempts in highly suicidal self-harming adolescents . On the basis of the criteria of 2 independent trials supporting efficacy , results support DBT as the first well-established , empirically supported treatment for decreasing repeated suicide attempts and self-harm in youths . Trial Registration Clinical Trials.gov Identifier : NCT01528020 OBJECTIVE This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder ( AOD ) and suicidality in a r and omized clinical trial . METHOD Forty adolescents ( Mage = 15 years ; 68 % female , 89 % White ) and their families recruited from an inpatient psychiatric hospital were r and omly assigned to an integrated outpatient cognitive-behavioral intervention for co-occurring AOD and suicidality ( I-CBT ) or enhanced treatment as usual ( E-TAU ) . Primary measures include the Schedule for Affective Disorders and Schizophrenia for School-Age Children , Suicide Ideation Question naire , Columbia Impairment Scale , Timeline Followback , Rutgers Alcohol Problem Index , and Rutgers Marijuana Problem Index . Assessment s were completed at pretreatment as well as 3 , 6 , 12 , and 18 months postenrollment . RESULTS In intent-to-treat analyses , I-CBT was associated with significantly fewer heavy drinking days and days of marijuana use relative to E-TAU but not with fewer drinking days . Those r and omized to I-CBT in comparison to E-TAU also reported significantly less global impairment as well as fewer suicide attempts , inpatient psychiatric hospitalizations , emergency department visits , and arrests . Adolescents across groups showed equivalent reductions in suicidal ideation . CONCLUSIONS I-CBT for adolescents with co-occurring AOD and suicidality is associated with significant improvement in both substance use and suicidal behavior , as well as markedly decreased use of additional health services including inpatient psychiatric hospitalizations and emergency department visits . Further testing of integrated protocol s for adolescent AOD and suicidality with larger and more diverse sample s is warranted |
11,178 | 31,083,783 | Additionally , there were no differences in postoperative quality of life score assessment at 3 and 6 months between robot-assisted radical cystectomy and open radical cystectomy .
Robot-assisted radical cystectomy is associated with less blood loss and lower transfusion rates .
There is no difference in complications , length of stay , mortality , and quality of life between robot-assisted radical cystectomy and open radical cystectomy . | To compare postoperative complications and health-related quality of life of patients undergoing robot-assisted radical cystectomy with those of patients undergoing open radical cystectomy . | PURPOSE Robotic assisted laparoscopic radical cystectomy for bladder cancer has been reported with potential for improvement in perioperative morbidity compared to the open approach . However , most studies are retrospective with significant selection bias . MATERIAL S AND METHODS A pilot prospect i ve r and omized trial evaluating perioperative outcomes and oncologic efficacy of open vs robotic assisted laparoscopic radical cystectomy for consecutive patients was performed from July 2009 to June 2011 . RESULTS To date 47 patients have been r and omized with data available on 40 patients for analysis . Each group was similar with regard to age , gender , race , body mass index and comorbidities , as well as previous surgeries , operative time , postoperative complications and final pathological stage . We observed no significant differences between oncologic outcomes of positive margins ( 5 % each , p = 0.50 ) or number of lymph nodes removed for open radical cystectomy ( 23 , IQR 15 - 28 ) vs robotic assisted laparoscopic radical cystectomy ( 11 , IQR 8.75 - 21.5 ) groups ( p = 0.135 ) . The robotic assisted laparoscopic radical cystectomy group ( 400 ml , IQR 300 - 762.5 ) was noted to have decreased estimated blood loss compared to the open radical cystectomy group ( 800 ml , IQR 400 - 1,100 ) and trended toward a decreased rate of excessive length of stay ( greater than 5 days ) ( 65 % vs 90 % , p = 0.11 ) compared to the open radical cystectomy group . The robotic group also trended toward fewer transfusions ( 40 % vs 50 % , p = 0.26 ) . CONCLUSIONS Our study vali date s the concept of r and omizing patients with bladder cancer undergoing radical cystectomy to an open or robotic approach . Our results suggest no significant differences in surrogates of oncologic efficacy . Robotic assisted laparoscopic radical cystectomy demonstrates potential benefits of decreased estimated blood loss and decreased hospital stay compared to open radical cystectomy . Our results need to be vali date d in a larger multicenter prospect i ve r and omized clinical trial Introduction : Open radical cystectomy ( ORC ) has been the st and ard treatment for muscle-invasive bladder cancer , but this is associated with significant morbidity and mortality . Robot-assisted radical cystectomy ( RARC ) has been proposed as minimally invasive alternative with improved morbidity and acceptable oncological outcomes , but a large series featuring RARC and their comparison with ORC is still lacking in India despite more than a decade of its inception . We have conducted this study with an objective to see the feasibility of RARC in the Indian context and compare it with contemporary st and ard . Methods : This is a prospect i ve cohort study conducted at two tertiary cancer institutes . We have evaluated the patients pertaining to operative and early post-operative factors from January 2014 to December 2015 . Necessary statistical tests applied to see comparability of the arms and their outcomes . Results : A total of 170 patients underwent surgery for carcinoma bladder ( 45 ORC while 125 RARC ) . Intraoperative blood loss ( RARC and ORC : 228 and 529 ml ) and average transfusion rate were lower with RARC . A trend towards benefit was noted in favour of robotic arm in terms of mean complication rate ( RARC and ORC : 54 and 39 % ) . Conclusions : The present study has shown comparable surgical and early post-operative outcomes with clear advantage of robotic approach in terms of intraoperative blood transfusion and lymph node yield . Although the study was non-r and omised in nature , it should provide substantial evidence on safety and feasibility of RARC in the Indian context and a reference point of evidence to look ahead Introduction : Open radical cystectomy ( RC ) is associated with significant morbidity and the role of minimally invasive surgery ( MIS ) in reducing morbidity of RC is controversial A direct comparison of various surgical modalities on perioperative outcomes is lacking in the Indian literature . We evaluated outcomes of minimally invasive ( robotic and laparoscopic ) versus open RC with pelvic lymph node dissection ( PLND ) performed at our institute from 2014 to 2016 . Methods : Eighty-three patients of RC with PLND were prospect ively analyzed from December 2014 to February 2016 . All patients of muscle invasive urothelial cancer of the bladder undergoing RC ( open or MIS ) were included in the study . Based on patients preference they were assigned to one of the three groups ( Open RC , robot-assisted RC , or laparoscopic RC ) . Their demographic profile , preoperative disease stage , operative data like operative time , blood loss , intraoperative complications , histopathological data like pathological stage , lymph-node yield etc . , postoperative complications if any and total duration of stay were recorded . These data of laparoscopic , open , and robotic cystectomies were compared in terms of various demographic , histopathologic parameters and perioperative outcomes . Results : Twenty-nine patients ( 34.93 % ) underwent minimally invasive RC with PLND ( 5 laparoscopic and 24 robotic ) . The median age of patients was 58 years . Mean number of lymph nodes removed was 22.5 ± 14.6 . The total number of lymph nodes removed in laparoscopic surgery was 104 with a yield of 20.6 per patient , in robotic surgery were 627 with a yield of 26.1 per patient , and in open surgery were 1119 with a yield of 20.7 per patient ( P = 0.004 ) . Clavien-Dindo Grade 2 and 3 complications were seen in 37.5 % of robotic , 60 % of laparoscopic , and 55.54 % of open RC . Average blood loss and operative time in laparoscopic , robotic , and open RC were 511.53 ± 311.02 ml , 552.08 ± 267.63 ml , and 512.05 ± 213.9 ml and 8.23 ± 1.36 h ( hrs ) , 7.53 ± 1.92 h , and 5.85 ± 1.76 h , respectively ( P = 0.68 and < 0.001 , respectively ) . Conclusions : MIS is associated with significantly longer operative time than open RC . Robotic RC has significantly higher lymph node yield than open or laparoscopic RC . Minimally invasive RC is equivalent to open surgery in terms of perioperative morbidity , mortality , and blood loss OBJECTIVE To evaluate our initial robotic-assisted radical cystectomy ( RARC ) experience compared with a robust open radical cystectomy ( ORC ) series performed at a single institution using a matched-pair analysis . Although early results suggest that RARC is safe , with favorable perioperative and early oncologic outcomes , limited data exist comparing ORC and RARC . METHODS RARC and ORC patients were identified through a prospect ively maintained institutional review board-approved bladder cancer data base . RARC and ORC cases performed from September 2007 to November 2010 were matched 1:2 by age , sex , urinary diversion , and clinical stage . The perioperative , complication , and pathologic outcomes were compared . RESULTS A total of 50 RARC and 100 ORC cases were review ed , with a median follow-up of 8 and 13.5 months , respectively . No differences in the demographic parameters were present between the 2 groups . RARC was associated with a significantly decreased median estimated blood loss ( 350 vs 475 mL ) and 30-day transfusion rate ( 2 % vs 24 % ) but with longer operative times ( 454.9 vs 349.1 minutes ) . No difference was found in the rate of 30-day minor or major Clavien complications , length of stay , or 30-day readmissions between groups . The 90-day mortality rate was 3 % versus 0 % for ORC and RARC , respectively . No difference in the final pathologic findings , number of lymph nodes removed , or margin status was identified . CONCLUSION Early experience with RARC compared with a robust ORC experience demonstrated similar perioperative and pathologic outcomes . Continued experience with RARC has the potential to bring improved perioperative results To compare health‐related quality ‐of‐life ( HRQoL ) outcomes for robot‐assisted laparoscopic radical cystectomy ( RARC ) with those of traditional open radical cystectomy ( ORC ) in a prospect i ve r and omised fashion Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND More than a decade since its inception , the benefits and cost efficiency of robot-assisted radical prostatectomy ( RARP ) continue to elicit controversy . OBJECTIVE To compare outcomes and costs between RARP and open RP ( ORP ) . DESIGN , SETTING , AND PARTICIPANTS A cohort study of 629 593 men who underwent RP for localized prostate cancer at 449 hospitals in the USA from 2003 to 2013 , using the Premier Hospital Data base . INTERVENTION RARP was ascertained through a review of the hospital charge description master for robotic supplies . OUTCOME MEASURES AND STATISTICAL ANALYSIS Outcomes were 90-d postoperative complications ( Clavien ) , blood product transfusions , operating room time ( ORT ) , length of stay ( LOS ) , and direct hospital costs . Propensity-weighted regression analyses accounting for clustering by hospitals and survey weighting ensured nationally representative estimates . RESULTS AND LIMITATIONS RARP utilization rapidly increased from 1.8 % in 2003 to 85 % in 2013 ( p<0.001 ) . RARP patients ( n=311 135 ) were less likely to experience any complications ( odds ratio [ OR ] 0.68 , p<0.001 ) or prolonged LOS ( OR 0.28 , p<0.001 ) , or to receive blood products ( OR 0.33 , p=0.002 ) compared to ORP patients ( n=318 458 ) . The adjusted mean ORT was 131min longer for RARP ( p=0.002 ) . The 90-d direct hospital costs were higher for RARP ( + $ 4528 , p<0.001 ) , primarily attributed to operating room and supplies costs . Costs were no longer signficantly different between ORP and RARP among the highest-volume surgeons ( ≥104 cases/yr ; + $ 1990 , p=0.40 ) and highest-volume hospitals ( ≥318 cases/yr ; + $ 1225 , p=0.39 ) . Limitations include the lack of oncologic characteristics and the retrospective nature of the study . CONCLUSIONS Our contemporary analysis reveals that RARP confers a perioperative morbidity advantage at higher cost . In the absence of large r and omized trials because of the widespread adoption of RARP , this retrospective study represents the best available evidence for the morbidity and cost profile of RARP versus ORP . PATIENT SUMMARY In this large study of men with prostate cancer who underwent either open or robotic radical prostatectomy , we found that robotic surgery has a better morbidity profile but costs more AIM In this study , we compared perioperative and oncologic outcomes of patients treated with either open or robot-assisted radical cystectomy and intracorporeal neobladder at a tertiary care center . METHODS The institutional prospect i ve bladder cancer data base was queried for " cystectomy with curative intent " and " neobladder " . All patients underwent robot-assisted radical cystectomy and intracorporeal neobladder or open radical cystectomy and orthotopic neobladder for high- grade non-muscle invasive bladder cancer or muscle invasive bladder cancer with a follow-up length ≥2 years were included . A 1:1 propensity score matching analysis was used . Kaplan-Meier method was performed to compare oncologic outcomes of selected cohorts . Survival rates were computed at 1,2,3 and 4 years after surgery and the log rank test was applied to assess statistical significance between the matched groups . RESULTS Overall , 363 patients ( 299 open and 64 robotic ) were included . Open radical cystectomy patients were more frequently male ( p = 0.08 ) , with higher pT stages ( p = 0.003 ) , lower incidence of urothelial histologies ( p = 0.05 ) and lesser adoption of neoadjuvant chemotherapy ( < 0.001 ) . After applying the propensity score matching , 64 robot-assisted radical cystectomy patients were matched with 46 open radical cystectomy cases ( all p ≥ 0.22 ) . Open cohort showed a higher rate of perioperative overall complications ( 91.3 % vs 42.2 % , p 0.001 ) . At Kaplan-Meier analysis robotic and open cohorts displayed comparable disease-free survival ( log-rank p = 0.746 ) , cancer-specific survival ( p = 0.753 ) and overall-survival rates ( p = 0.909 ) . CONCLUSIONS Robot-assisted radical cystectomy and intracorporeal neobladder provides comparable oncologic outcomes of open radical cystectomy and orthotopic neobladder at intermediate term survival analysis OBJECTIVES To assess the surgical and oncological outcome of robot-assisted radical cystectomy ( RARC ) compared with open radical cystectomy ( ORC ) . PATIENTS AND METHODS Clinical data of 64 patients undergoing RARC between August 2010 and August 2013 were prospect ively documented and retrospectively compared with 79 patients undergoing ORC between August 2008 and August 2013 at a single academic institution . Perioperative results , surgical margins status , and nodal yield after RARC and ORC were compared using Mann-Whitney U test ( continuous variables ) and chi-square test ( categorical variables ) . Additional age-stratified analysis was performed in elderly patients ( ≥75 y ) . To avoid inference errors by multiple testing , P-values were adjusted using Bonferroni׳s correction . RESULTS Baseline characteristics of both cohorts were balanced . RARC patients had significantly less blood loss ( RARC : 300 [ interquartile range { IQR } : 200 - 500]ml ; perioperative transfusion rate : 0 [ IQR : 0 - 2 ] red packed blood cells [ RPBCs ] ; ORC : 800 [ IQR : 500 - 1200]ml , P<0.01 ; transfusion rate : 3 [ IQR : 2 - 4 ] RPBCs , P<0.01 ) , and hospital stay of RARC patients was reduced by 20 % ( RARC : 13 [ IQR : 9 - 17]d , ORC : 16 [ IQR : 13 - 21]d , P < 0.01 ) . A total of 55 patients who underwent RARC and 59 patients who underwent ORC were eligible for analysis of oncological surrogates " surgical margin status " and " lymph-node yield " as well as for survival data . No differences between patients undergoing RARC or ORC were observed . In elderly patients ( ≥75 y ; RARC : 17 patients , ORC : 28 patients ) , decreased intraoperative blood loss ( RARC : 300 [ IQR : 100 - 475]ml ; ORC : 800 [ IQR : 400 - 1300]ml , P<0.01 ) and lower transfusion rate ( RARC : 0 [ IQR : 0 - 1 ] RPBCs ; ORC : 4 [ IQR : 2 - 5 ] RPBCs , P<0.01 ) were observed in the robotic group . Major limitations of this study are the retrospective study design and a potential selection bias . CONCLUSIONS RARC provides significant advantages compared with ORC regarding blood loss and postoperative recovery , whereas surgical and oncological outcomes are not different BACKGROUND Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer ( BCa ) . However , reduction in postoperative morbidity relative to the open approach has not been demonstrated . OBJECTIVE To compare complication rates in patients undergoing robotic versus open radical cystectomy ( RC ) . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC , 83 robotic RC . INTERVENTION Open or robotic RC with urinary diversion . MEASUREMENTS Demographic , perioperative , and complication data were recorded prospect ively . Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale . Data were evaluated using chi(2 ) and multivariate logistic regression analyses . RESULTS AND LIMITATIONS At 30 d , the open group demonstrated a higher overall complication rate ( 59 % vs 41 % ; p=0.04 ) as well as more major complications ( 30 % vs 10 % ; p=0.007 ) . At 90 d , the overall complication rate was greater in the open group , but this was not statistically significant ( 62 % vs 48 % ; p=0.07 ) . However , there was a significantly higher major complication rate in the open cohort ( 31 % vs 17 % ; p=0.03 ) . When subjected to logistic regression analysis , robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists ( ASA ) score ( 3 - 4 ) and longer surgical time were independent predictors of major complications . Though this is one of the largest published RC series , the sample size is relatively small . Moreover , despite the two patient cohorts being similarly matched , the study was not performed in a r and omized fashion . CONCLUSIONS Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy . Robotic cystectomy is an independent predictor of fewer overall and major complications . Until long-term oncologic results are available , robotic cystectomy should still be considered investigational PURPOSE The aim of our study was to compare early complication rates between the robot-assisted radical cystectomy ( RARC ) and open radical cystectomy ( ORC ) using a st and ardized reporting system . PATIENTS AND METHODS From September 2008 to March 2011 , 35 and 104 patients underwent ORC and RARC , respectively . Demographics and perioperative and complication data on all patients were review ed retrospectively and compared between the two groups . All complications were categorized using a modified Clavien reporting system . We also sought to identify independent predictive factors of grade II or greater complications . RESULTS There were no significant differences between the ORC and RARC groups with regard to age , body mass index , American Society of Anesthesiologists score , clinical stage , surgical procedure history , or sex . The RARC group had more cases of ileal neobladder urinary diversion ( P<0.001 ) . We did not find any differences in terms of pathologic stage or length of stay . The ORC group had more grade II or greater complications ( P=0.001 ) , wound problems ( P=0.043 ) , multiple complications ( P=0.014 ) , greater estimated blood loss ( EBL ) ( P<0.001 ) , and needed more transfusions ( P<0.001 ) . A longer operative time was needed in the RARC group , however . Multivariate logistic regression analysis demonstrated that the ORC ( P=0.045 , odds ratio [ 95 % confidence interval]=2.44 [ 1.02 - 5.85 ] ) , EBL ( > 500 mL , P=0.013 , 2.75 [ 1.24 - 6.10 ] ) , and female sex ( P=0.028 , 4.06 [ 1.12 - 14.11 ] ) were independent predictors of grade II or greater complications . CONCLUSIONS Our results showed that the RARC group was comparable to the ORC group with respect to complications using the Clavien reporting system . Further long-term and r and omized trials are needed , however , because RARC is still not considered the st and ard therapy for bladder cancer BACKGROUND Open radical cystectomy ( ORC ) and urinary diversion in patients with bladder cancer ( BCa ) are associated with significant perioperative complication risk . OBJECTIVE To compare perioperative complications between robot-assisted radical cystectomy ( RARC ) and ORC techniques . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve r and omized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy ( RC ) , pelvic lymph node dissection ( PLND ) , and urinary diversion . Patients were r and omized to ORC/PLND or RARC/PLND , both with open urinary diversion . Patients were followed for 90 d postoperatively . INTERVENTION St and ard ORC or RARC with PLND ; all urinary diversions were performed via an open approach . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcomes were overall 90-d grade 2 - 5 complications defined by a modified Clavien system . Secondary outcomes included comparison of high- grade complications , estimated blood loss , operative time , pathologic outcomes , 3- and 6-mo patient-reported quality -of-life ( QOL ) outcomes , and total operative room and inpatient costs . Differences in binary outcomes were assessed with the chi-square test , with differences in continuous outcomes assessed by analysis of covariance with r and omization group as covariate and , for QOL end points , baseline score . RESULTS AND LIMITATIONS The trial enrolled 124 patients , of whom 118 were r and omized and underwent RC/PLND . Sixty were r and omized to RARC and 58 to ORC . At 90 d , grade 2 - 5 complications were observed in 62 % and 66 % of RARC and ORC patients , respectively ( 95 % confidence interval for difference , -21 % to -13 % ; p=0.7 ) . The similar rates of grade 2 - 5 complications at our m and ated interim analysis met futility criteria ; thus , early closure of the trial occurred . The RARC group had lower mean intraoperative blood loss ( p=0.027 ) but significantly longer operative time than the ORC group ( p<0.001 ) . Pathologic variables including positive surgical margins and lymph node yields were similar . Mean hospital stay was 8 d in both arms ( st and ard deviation , 3 and 5 d , respectively ; p=0.5 ) . Three- and 6-mo QOL outcomes were similar between arms . Cost analysis demonstrated an advantage to ORC compared with RARC . A limitation is the setting at a single high-volume , referral center ; our findings may not be generalizable to all setting s. CONCLUSIONS This trial failed to identify a large advantage for robot-assisted techniques over st and ard open surgery for patients undergoing RC/PLND and urinary diversion . Similar 90-d complication rates , hospital stay , pathologic outcomes , and 3- and 6-mo QOL outcomes were observed regardless of surgical technique . PATIENT SUMMARY Of 118 patients with bladder cancer who underwent radical cystectomy , pelvic lymph node dissection , and urinary diversion , half were r and omized to open surgery and half to robot-assisted laparoscopic surgery . We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups . TRIAL REGISTRATION Clinical Trials.gov identifier NCT01076387 , www . clinical trials.gov INTRODUCTION The role of minimally invasive radical cystectomy as opposed to open surgery for bladder cancer is not yet established . We present comparative outcomes of open , laparoscopic and robotic-assisted radical cystectomy MATERIAL AND METHODS Prospect i ve cohort comparison of 158 patients from 2003 - 2008 undergoing open radical cystectomy ( ORC ) ( n = 52 ) , laparoscopic radical cystectomy ( LRC ) ( n = 58 ) or robotic-assisted radical cystectomy ( RARC ) ( n = 48 ) performed by a team of three surgeons at two hospitals . Peri-operative data , complication rates , length of hospital stay , oncological outcome ( including lymph node status ) and survival were recorded . Statistical analyses were adjusted to account for potential confounding factors such as ASA grade , gender , age , diversion type and final histology . RESULTS RARC took longer than LRC and ORC . Patients were about 30 times more likely to have a transfusion if they had ORC than if they had RARC ( p < 0.0001 ) and about eight times more likely to have a transfusion if they had LRC compared with RARC ( p < 0.006 ) . Patients were four times more likely to have a transfusion if they had ORC as compared with LRC ( p < 0.007 ) . Patients were four times more likely to have complications if they had ORC than RARC ( p = 0.006 ) and about three times more likely to have complications with LRC than with RARC ( p = 0.02 ) . Hospital stay was mean 19 days after ORC , 16 days after LRC and 10 days after RARC . CONCLUSIONS Despite study limitations , RARC had the lowest transfusion and complication rates and the shortest length of stay , although taking the longest to perform BACKGROUND Robot-assisted radical cystectomy ( RARC ) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer . OBJECTIVE We sought to define the learning curve for RARC by evaluating results from a multicenter , contemporary , consecutive series of patients who underwent this procedure . DESIGN , SETTING , AND PARTICIPANTS Utilizing the International Robotic Cystectomy Consortium data base , a prospect ively maintained and institutional review board-approved data base , we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009 . MEASUREMENTS Cut-off points for operative time , lymph node yield ( LNY ) , estimated blood loss ( EBL ) , and margin positivity were identified . Using specifically design ed statistical mixed models , we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points . RESULTS AND LIMITATIONS Mean operative time was 386 min , mean EBL was 408 ml , and mean LNY was 18 . Overall , 34 of 482 patients ( 7 % ) had a positive surgical margin ( PSM ) . Using statistical models , it was estimated that 21 patients were required for operative time to reach 6.5h and 8 , 20 , and 30 patients were required to reach an LNY of 12 , 16 , and 20 , respectively . For all patients , PSM rates of < 5 % were achieved after 30 patients . For patients with pathologic stage higher than T2 , PSM rates of < 15 % were achieved after 24 patients . CONCLUSIONS RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers . This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality BACKGROUND In recent years , surgeons have begun to report case series of minimally invasive approaches to radical cystectomy , including robotic-assisted techniques demonstrating the surgical feasibility of this procedure with the potential of lower blood loss and more rapid return of bowel function and hospital discharge . Despite these experiences and observations , at this point high levels of clinical evidence with regard to the benefits of robotic cystectomy are absent , and the current experiences represent case series with limited comparisons to historical controls at best . OBJECTIVE We report our results on a prospect i ve r and omized trial of open versus robotic-assisted laparoscopic radical cystectomy with regard to perioperative outcomes , complications , and short-term narcotic usage . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve r and omized single-center noninferiority study comparing open versus robotic approaches to cystectomy in patients who are c and i date s for radical cystectomy for urothelial carcinoma of the bladder . Of the 41 patients who underwent surgery , 21 were r and omized to the robotic approach and 20 to the open technique . INTERVENTION Radical cystectomy , bilateral pelvic lymphadenectomy , and urinary diversion by either an open approach or by a robotic-assisted laparoscopic technique . MEASUREMENTS The primary end point was lymph node ( LN ) yield with a noninferiority margin of four LNs . Secondary end points included demographic characteristics , perioperative outcomes , pathologic results , and short-term narcotic use . RESULTS AND LIMITATIONS On univariate analysis , no significant differences were found between the two groups with regard to age , sex , body mass index , American Society of Anesthesiologists classification , anticoagulation regimen of aspirin , clinical stage , or diversion type . Significant differences were noted in operating room time , estimated blood loss , time to flatus , time to bowel movement , and use of inpatient morphine sulfate equivalents . There was no significant difference in regard to overall complication rate or hospital stay . On surgical pathology , in the robotic group 14 patients had pT2 disease or higher ; 3 patients had pT3/T4 disease ; and 4 patients had node-positive disease . In the open group , eight patients had pT2 disease or higher ; five patients had pT3/T4 disease ; and seven patients had node-positive disease . The mean number of LNs removed was 19 in the robotic group versus18 in the open group . Potential study limitations include the limited clinical and oncologic follow-up and the relatively small and single-institution nature of the study . CONCLUSIONS We present the results of a prospect i ve r and omized controlled noninferiority study with a primary end point of LN yield , demonstrating the robotic approach to be noninferior to the open approach . The robotic approach also compares favorably with the open approach in several perioperative parameters BACKGROUND Radical cystectomy is the surgical st and ard for invasive bladder cancer . Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity . We aim ed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy . METHODS The RAZOR study is a r and omised , open-label , non-inferiority , phase 3 trial done in 15 medical centres in the USA . Eligible participants ( aged ≥18 years ) had biopsy-proven clinical stage T1-T4 , N0-N1 , M0 bladder cancer or refractory carcinoma in situ . Individuals who had previously had open abdominal or pelvic surgery , or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded . Patients were central ly assigned ( 1:1 ) via a web-based system , with block r and omisation by institution , stratified by type of urinary diversion , clinical T stage , and Eastern Cooperative Oncology Group performance status , to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion . Treatment allocation was only masked from pathologists . The primary endpoint was 2-year progression-free survival , with non-inferiority established if the lower bound of the one-sided 97·5 % CI for the treatment difference ( robotic cystectomy minus open cystectomy ) was greater than -15 percentage points . The primary analysis was done in the per- protocol population . Safety was assessed in the same population . This trial is registered with Clinical Trials.gov , number NCT01157676 . FINDINGS Between July 1 , 2011 , and Nov 18 , 2014 , 350 participants were r and omly assigned to treatment . The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients . 17 ( 10 % ) of 176 patients in the robotic cystectomy group did not have surgery and nine ( 5 % ) patients had a different surgery to that they were assigned . 21 ( 12 % ) of 174 patients in the open cystectomy group did not have surgery and one ( 1 % ) patient had robotic cystectomy instead of open cystectomy . Thus , 302 patients ( 150 in the robotic cystectomy group and 152 in the open cystectomy group ) were included in the per- protocol analysis set . 2-year progression-free survival was 72·3 % ( 95 % CI 64·3 to 78·8 ) in the robotic cystectomy group and 71·6 % ( 95 % CI 63·6 to 78·2 ) in the open cystectomy group ( difference 0·7 % , 95 % CI -9·6 % to 10·9 % ; pnon-inferiority=0·001 ) , indicating non-inferiority of robotic cystectomy . Adverse events occurred in 101 ( 67 % ) of 150 patients in the robotic cystectomy group and 105 ( 69 % ) of 152 patients in the open cystectomy group . The most common adverse events were urinary tract infection ( 53 [ 35 % ] in the robotic cystectomy group vs 39 [ 26 % ] in the open cystectomy group ) and postoperative ileus ( 33 [ 22 % ] in the robotic cystectomy group vs 31 [ 20 % ] in the open cystectomy group ) . INTERPRETATION In patients with bladder cancer , robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival . Increased adoption of robotic surgery in clinical practice should lead to future r and omised trials to assess the true value of this surgical approach in patients with other cancer types . FUNDING National Institutes of Health National Cancer Institute OBJECTIVE In Japan , no study has compared the perioperative outcomes observed between robot-assisted radical cystectomy ( RARC ) and open radical cystectomy ( ORC ) . This study aim ed at a prospect i ve comparison of the perioperative outcomes between RARC and ORC performed by a single surgeon . METHODS Between 2008 and 2011 , 26 bladder cancer patients underwent radical cystectomy by one surgeon , 11 robotically and 15 by open procedure . We prospect ively collected perioperative and pathological data for these 26 patients , and retrospectively compared these two different surgical procedures . RESULTS The RARC cohort had a significant decrease in both estimated blood loss ( 656.9 vs. 1788.7 ml , P=0.0015 ) and allogeneic transfusion requirement ( 0 vs. 40 % , P=0.0237 ) . The total operative time was almost the same ( P=0.2306 ) but increased duration of bladder removal and lymphadenectomy was observed in the RARC cohort ( P=0.0049 ) . Surgery-related complication rates within 30 days were not significantly different ( P=0.4185 ) . Positive surgical margin was observed in three patients in the ORC cohort and in one patient in the RARC cohort ( P=0.4664 ) . The RARC cohort had a larger number of removed lymph nodes than the ORC cohort , and the difference was statistically significant ( 20.7 vs. 13.8 , P=0.0421 ) . CONCLUSIONS We confirmed that RARC is safe and yields acceptable outcomes in comparison with ORC for the treatment of bladder cancer if it is performed by a surgeon who has experience of over 60 cases of robot-assisted radical prostatectomy . It is hoped that RARC will gain acceptance in Japan as a minimally invasive surgery for muscle-invasive bladder cancer INTRODUCTION Treatment for muscle-invasive bladder cancer ( MIBC ) remains highly morbid despite improving surgical techniques . As the median age of diagnosis is 73 , many patients are elderly at the time of cystectomy . We compare perioperative surgical outcomes in elderly patients undergoing robotic vs open radical cystectomy ( RC ) . MATERIAL S AND METHODS Patients > 75 years at time of RC were identified . Demographic , clinicopathologic , and perioperative variables were examined . Estimated blood loss ( EBL ) and length of stay ( LOS ) data were collected with multivariate linear regression analysis performed to assess whether technique was independently associated with outcomes . RESULTS Eighty-seven patients > 75 years of age underwent cystectomy for MIBC ( 58 open , 29 robotic ) . Mean age was 79.6 ( ±3.2 ) and 79.2 ( ±3.5 ) for open and robotic groups , respectively ( p = 0.64 ) . There were no significant differences in baseline comorbidities , clinical or pathologic stage , or use of neoadjuvant chemotherapy . The mean number of lymph nodes removed was similar ( p = 0.08 ) . Robotic cystectomy had significantly longer mean OR times ( p < 0.001 ) . On multivariate analyses , robotic surgery was associated with -389cc less EBL ( 95 % CI -547 to -230 , p < 0.001 ) and a -1.5-day-shortened LOS ( 95%CI -2.9 to -0.2 , p = 0.02 ) compared with open surgery . There were no significant differences in surgical complications or 90-day readmission rates between the two groups . CONCLUSIONS Robotic cystectomy is safe and feasible in an elderly population . We observed longer OR times with robotic surgery , but with decreased EBL , shorter hospital stays , and comparable complication and readmission rates with open RC . Larger prospect i ve studies are required to confirm these findings |
11,179 | 26,356,655 | Moderate evidence was found to support the use of ASI . | This systematic review examines the literature published from January 2006 through April 2013 related to the effectiveness of Ayres Sensory Integration ® ( ASI ) and sensory-based interventions ( SBIs ) within the scope of occupational therapy for people with autism spectrum disorder to improve performance in daily life activities and occupations . | The purpose of this pilot study was to establish a model for r and omized controlled trial research , identify appropriate outcome measures , and address the effectiveness of sensory integration ( SI ) interventions in children with autism spectrum disorders ( ASD ) . Children ages 6 - 12 with ASD were r and omly assigned to a fine motor or SI treatment group . Pretests and posttests measured social responsiveness , sensory processing , functional motor skills , and social-emotional factors . Results identified significant positive changes in Goal Attainment Scaling scores for both groups ; more significant changes occurred in the SI group , and a significant decrease in autistic mannerisms occurred in the SI group . No other results were significant . The study discusses considerations for design ing future outcome studies for children with ASD This study evaluated a manualized intervention for sensory difficulties for children with autism , ages 4–8 years , using a r and omized trial design . Diagnosis of autism was confirmed using gold st and ard measures . Results show that the children in the treatment group ( n = 17 ) who received 30 sessions of the occupational therapy intervention scored significantly higher ( p = 0.003 , d = 1.2 ) on Goal Attainment Scales ( primary outcome ) , and also scored significantly better on measures of caregiver assistance in self-care ( p = 0.008 d = 0.9 ) and socialization ( p = 0.04 , d = 0.7 ) than the Usual Care control group ( n = 15 ) . The study shows high rigor in its measurement of treatment fidelity and use of a manualized protocol , and provides support for the use of this intervention for children with autism . Findings are discussed in terms of their implication s for practice and future research Enriched sensorimotor environments enable rodents to compensate for a wide range of neurological challenges , including those induced in animal models of autism . Given the sensorimotor deficits in most children with autism , we attempted to translate that approach to their treatment . In a r and omized controlled trial , 3 - 12 year-old children with autism were assigned to either a sensorimotor enrichment group , which received daily olfactory/tactile stimulation along with exercises that stimulated other paired sensory modalities , or to a control group . We administered tests of cognitive performance and autism severity to both groups at the initiation of the study and after 6 months . Severity of autism , as assessed with the Childhood Autism Rating Scale , improved significantly in the enriched group compared to controls . Indeed , 42 % of the enriched group and only 7 % of the control group had what we considered to be a clinical ly significant improvement of 5 points on that scale . Sensorimotor enrichment also produced a clear improvement in cognition , as determined by their Leiter-R Visualization and Reasoning scores . At 6 months , the change in average scores for the enriched group was 11.3 points higher than that for the control group . Finally , 69 % of parents in the enriched group and 31 % of parents in the control group reported improvement in their child over the 6-month study . Environmental enrichment therefore appears to be effective in ameliorating some of the symptoms of autism in children OBJECTIVES The objective of this study was to access whether there were any therapeutic effects of Thai Traditional Massage ( TTM ) on major behavioral and emotional disturbances in Thai autistic children . DESIGN This was a r and omized controlled trial study . SETTING S/LOCATION The study was conducted at the Rehabilitation Centre of the Thai Red Cross Society . SUBJECTS A total of 60 autistic children between the ages of 3 and 10 completed this study . INTERVENTIONS St and ard sensory integration therapy ( SI ) was compared to the SI with TTM treatments . OUTCOME MEASURES Parents and teachers assessed major behavior disturbances using the Conners ' Rating Scales at 0 and 8 weeks . Sleep Diary ( SD ) , recorded by the parents , assessed the patient 's sleeping patterns every week . RESULTS Sixty ( 60 ) autistic children , mean age 4.67 + /- 1.82 , were recruited . No statistical differences were seen in the demographic and baseline data among both groups . From both the Conners ' Teacher Question naire and SD , statistical improvement was detected for conduct problem , hyperactivity , inattention-passivity , hyperactivity index , and sleeping behavior . However , results from the Conners ' Parent Question naire revealed an improvement only for anxiety ( p = 0.04 ) in the massage group , whereas when both groups were compared , a significant improvement in conduct problem ( p = 0.03 ) and anxiety ( p = 0.01 ) was found . Results indicated that TTM may have a positive effect in improving stereotypical behaviors in autistic children . CONCLUSIONS Over a period of 8 weeks , our findings suggested that TTM could be used as a complementary therapy for autistic children in Thail and A mental health enterprise may be described by either ( a ) rather general philosophical total mental health goals , or ( b ) highly diverse and individualized patient-therapist goals . Goals a. have not provided a workable framework for program evaluation . This paper proposes that evaluation be done in the framework of goals b. by setting up , before treatment , a measurable scale for each patient-therapist goal , and specifying , for each patient , a transformation of his overall goal attainment into a st and ardized T-score . This method , together with r and om assignment of patients to treatment modes , was devised to permit comparison of treatment modes within a program , but it also provides a good basis for a judgmental evaluation of the total program This study investigated the effectiveness of a 20-week Simulated Developmental Horse-Riding Program ( SDHRP ) by using an innovative exercise equipment ( Joba ) on the motor proficiency and sensory integrative functions in 60 children with autism ( age : 6 years , 5 months to 8 years , 9 months ) . In the first phase of 20 weeks , 30 children received the SDHRP in addition to their regular occupational therapy while another 30 children received regular occupational therapy only . The arrangement was reversed in the second phase of another 20 weeks . Children with autism in this study showed improved motor proficiency and sensory integrative functions after 20-week SDHRP ( p < .01 ) . In addition , the therapeutic effect appeared to be sustained for at least 24 weeks ( 6 months ) The homeostatic theory of stereotyped behaviors assumes that these behaviors modulate arousal . Weighted vests are used to decrease stereotyped behaviors in persons with autism because the input they provide is thought to serve the same homeostatic function . This small-n , r and omized and blinded study measured the effects of wearing a weighted vest on stereotyped behaviors and heart rate for six children with autism in the classroom . Weighted vests did not decrease motoric stereotyped behaviors in any participant . Verbal stereotyped behaviors decreased in one participant . Weighted vests did not decrease heart rate . Heart rate increased in one participant . Based on this protocol , the use of weighted vests to decrease stereotyped behaviors or arousal in children with autism in the classroom was not supported |
11,180 | 29,481,401 | Conclusions : These findings demonstrate an association between Dupuytren disease and diabetes mellitus , liver disease , and epilepsy . | Background : The role of diabetes mellitus , liver disease , and epilepsy as risk factors for Dupuytren disease remains unclear .
In this systematic review and meta- analysis , the strength and consistency of these associations were examined . | To investigate the influence of alcohol on glucose counterregulation and recovery during acute insulin-induced hypoglycemia in type 2 diabetic subjects , 8 diet-treated type 2 diabetic subjects were examined twice after an overnight fast . A grade d hyperinsulinemic ( 1 mU/kg/min , 60 to 195 minutes ) euglycemic/hypoglycemic clamp was performed with concomitant infusion of 3-(3)H-glucose to assess glucose turnover . After a euglycemic baseline period ( 150 to 180 minutes ) , 200 mL of water was taken either alone or with alcohol ( 0.4 g/kg body weight ) . Hypoglycemia ( plasma glucose nadir , 2.8 mmol/L ) was subsequently induced , and the recovery period followed after discontinuation of insulin and the variable glucose infusion . On both study days , circulating concentrations of insulin and glucose were comparable . Alcohol intake markedly increased plasma lactate ( area under the curve [ AUC ] , recovery period ) ( 244 + /- 30 v 12 + /- 4 mmol/L x 240 minutes ; P = .00009 ) and suppressed plasma nonesterified fatty acids ( NEFA ) ( AUC , recovery period ) ( 95 + /- 13 v 161 + /- 18 mmol/L x 240 minutes ; P = .0008 ) . No differences were found in the counterregulatory response of catecholamines , cortisol , and growth hormone ( GH ) . However , alcohol intake decreased peak glucagon significantly ( 155 + /- 12 v 200 + /- 17 pg/mL ; P = .038 ) . In diet-treated , mild type 2 diabetic subjects , alcohol does not modify recovery from insulin-induced hypoglycemia Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports Dupuytren 's disease or palmar fibromatosis is a common disabling h and disorder , mainly confined to Caucasians of northwestern European origin . The prevalence of Dupuytren 's disease and possible risk factors related to the disease were evaluated in a r and om sample of 1297 males and 868 females , aged 46 to 74 years . Blood sample s were collected and biochemical parameters were evaluated . The possible relation between the disease and clinical , social , and biochemical parameters were estimated with age-adjusted univariate logistic regression analysis . Altogether 19.2 % of the males and 4.4 % of the female participants had clinical signs of Dupuytren 's disease . The prevalence increased with age , from 7.2 % among males in the age group 45 - 49 years up to 39.5 % in those 70 - 74 years old . The more severe form of the disease , finger contractures , was found in 5.0 % of the men and 1.4 % had required operation , while this was rarely seen among women . In men elevated fasting blood glucose ( P < 0.04 ) , low body weight , and body mass index were significantly correlated with the presence of the disease ( P < 0.001 ) . Dupuytren 's disease was common among heavy smokers ( P = 0.02 ) and those having manual labor as occupation ( P = 0.018 ) . These results show that Dupuytren 's disease is common in the Icel and ic population and occupation and lifestyle seem to be related to the disease A comparative prospect i ve study of 120 adult diabetics ( 60 insulin dependent , 60 non-insulin dependent ) and 120 non-diabetic adults as controls showed significantly higher incidence of Dupuytren 's disease , limited joint motion , carpal tunnel syndrome , and flexor tenosynovitis in the diabetic population . Of the diabetic patients one third had a mild non-progressive form of Dupuytren 's disease , which commonly involved the long and ring rays . Limited joint motion was noted in a third of diabetics , and carpal tunnel syndrome was observed in 15 - 25 % , and flexor tenosynovitis in about a fifth . Limited joint motion co-existed with Dupuytren 's disease in 57 % of insulin-dependent diabetics . Diabetic polyneuropathy was found in two thirds of insulin-dependent diabetics and in one third of non-insulin dependent diabetics . All these h and changes were more marked in insulin-dependent diabetics and they showed a positive correlation with increasing age of the patient , duration of the diabetes , and the presence of a microangiopathy This prospect i ve study was undertaken to assess the prevalence of Dupuytren 's contracture ( DC ) and its relationship with possible causes , especially alcohol consumption and chronic liver disease . Four hundred thirty-two consecutively hospitalized patients were examined for evidence of DC . They were divided into five groups based on the following clinical , biologic , and histologic criteria : alcoholic cirrhosis ( 89 patients ) , noncirrhotic alcoholic liver disease ( 55 patients ) , chronic alcoholism without liver disease ( 46 patients ) , nonalcoholic chronic liver disease ( 68 patients ) , and a control group ( 174 patients ) . The prevalence of DC in these five groups of patients was 32.5 % , 22 % , 28 % , 6 % , and 12 % , respectively ; the prevalence of DC was higher in patients with cirrhotic or noncirrhotic alcoholic liver disease ( 25.5 % ) than it was in patients with nonalcoholic liver disease ( 6 % ) , but it was not significantly different in alcoholic patients with or without liver disease . The relationship between DC and age , sex , manual labor , previous h and injuries , diabetes mellitus , alcohol consumption , and cigarette smoking was assessed by univariate and logistic regression methods . Nine variables were significantly different in patients with or without DC : age , sex , manual labor , previous h and injuries , diabetes mellitus , daily alcohol consumption , duration of alcohol consumption , total alcohol consumption , and duration of cigarette smoking . In our patients , variables that could explain DC were , in decreasing order , age , total alcohol consumption , sex ( male ) , and previous h and injuries . In alcoholic patients , these variables were age and previous h and injuries ; in nonalcoholic patients , these variables were age and cigarette smoking . These results emphasize the high prevalence of DC in alcoholic patients and the absence of a correlation between DC and chronic liver disease . Age and alcohol consumption are the best explanatory variables of DC in hospitalized patients The musculoskeletal complications of diabetes mellitus ( DM ) , which are the most common endocrine arthropathy , have been generally ignored and poorly treated compared with other complications such as neuropathy , retinopathy and nephropathy . Like other quality of life issues , the musculoskeletal disability of DM has not been investigated effectively . The incidence of diabetic foot has decreased thanks to excellent foot care , but the h and is still an important target for diabetic complications . The aim of this study was to investigate early diabetic musculoskeletal complications on the basis of a collaborative multidisciplinary study design . For this purpose 78 patients ( mean age 57.8 ± 11.9 years , 55 women and 23 men ) who had type II DM for 15 years maximally and 37 non-diabetic controls ( mean age : 55.7 ± 11.5 , 27 women and 10 men ) were r and omly selected for inclusion in the study . All patients were evaluated by the Rheumatology , Orthopedic Rehabilitation and H and Rehabilitation Divisions . Dupuytren 's disease was present in 17 ( 21.8 % ) of 78 diabetic subjects as the most frequent and statistically significant complication of the musculoskeletal system . In correlation and logistic regression analysis , only retinopathy was significantly associated with duration of diabetes and diabetic foot . Long-term prospect i ve r and omised controlled trials on the effects of exercise in preventing musculoskeletal complications and disability in diabetics are needed Sixty Type 1 ( insulin dependent ) and sixty Type 2 ( non insulin dependent ) diabetic patients attending a diabetology unit were examined in search of limited joint mobility , Dupuytren 's disease , flexor tenosynovitis and carpal tunnel syndrome , in comparison with two population s of 60 non diabetic controls matched for sex and age with the Type 1 and the Type 2 diabetic patients . Microangiopathic and neuropathic complications , glycaemic control , blood pressure and tobacco consumption were simultaneously assessed in 39 of the 60 type 1 and in all the type 2 diabetic patients . The prevalence of the various soft tissue h and lesions was higher in both diabetic population s ( respectively Type 1 and Type 2 ) than in their control population s : Limited joint mobility : 33.3 and 26.7 % vs 5.0 and 8.3 % ( both p < 0.01 ) ; Dupuytren 's disease : 35.0 and 30.0 % vs 6.7 and 10.0 % ( both p < 0.01 ) ; flexor tenosynovitis : 23.3 and 16.7 % vs 0.0 and 3.3 % ( p < 0.01 and p < 0.05 ) ; carpal tunnel syndrome : 26.7 and 15.0 % vs 3.3 and 5 % ( p < 0.01 and NS ) . The prevalence of limited joint mobility in Type 1 diabetes was independently associated with increasing age ( p < 0.05 ) and to lower extent with increasing duration of diabetes ( p = 0.05 ) , whereas the prevalence of Dupuytren 's disease only correlated with increasing age in both types of diabetes ( p < 0.05 ) . In Type 2 diabetes , the prevalence of flexor tenosynovitis also increased independently with age ( p < 0.05 ) , and the prevalence of limited joint mobility increased in the opposite way to the body mass index after adjustment on age , duration of diabetes and sex ( p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Development of Dupuytren 's contractures , frozen shoulder , Ledderhose 's syndrome , Peyronie 's disease , fibromas , and general joint pain has been linked in retrospective studies and case reports to the use of antiepileptic drugs . We undertook a prospect i ve survey of the incidence of connective tissue disorders in 622 patients newly treated with carbamazepine , phenobarbital , phenytoin sodium , or primidone . Ten of the 406 patients who were treated for 6 months or more developed connective tissue disorders . All affected patients were taking a barbiturate ( primidone , 4 patients ; phenobarbital , 6 patients ) . Seven of the 10 problems occurred during the first year of treatment . These data are prospect i ve evidence of a statistically significant relationship between barbiturate use and the development of connective tissue disorders , and timing of appearance A study of 197 epileptic out patients consecutively observed by one Neurologist allowed a prospect i ve study of the side effects of antiepileptic drugs . This study shows essentially that a clinical improvement comparable to that generally reported can be obtained with side effects limited in their number and intensity . The main principle is the routine search of these effects which are not always spontaneously mentioned by the patients , especially intellectual slowness and loss of sexual activity . The detection of the side effects through history and physical examination is far more fruitful than are plasma concentrations of drugs which can be doubly misleading : some plasma concentrations lower than recognized therapeutical levels are efficient however while others are higher and nevertheless necessary and well tolerated . Among the side effects specific to certain antiepileptic drugs , shoulder-h and syndrome due to phenobarbital was noted in 10 per cent of the cases . Furthermore , the frequency of scapulo-humeral periarthritis was significantly higher in the epileptic group than in the controls . Dupuytren 's disease was less frequent ( 8 per cent ) and the difference with the controls was not significant . Among the non-specific side effects , nystagmus is a somewhat useful sign in treatments by phenytoin but as with drugs dosages , it must be weighed within the whole clinical picture Prospect i ve study of 280 diabetic adults and 100 control show an association of limited joint mobility ( LJM ) with Dupuytren 's contracture ( DC ) in 37 diabetic and no one of control case . In 80 diabetic with LJM , DC is found in 46.25 p. cent against 21 p. cent in 200 diabetic without LJM ( p less than 0.00003 ) . LJM and DC are significantly related to diabetic retinopathy and neuropathy . Their coexistence in diabetic patients , reported by other authors may be related to diffuse alteration of diabetic connective tissue |
11,181 | 18,722,149 | 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 ) . | OBJECTIVE To develop clinical practice guidelines for the use of foot orthotics ( FO ) in the treatment of knee and hip osteoarthritis . | OBJECTIVE To assess the radiographic and symptomatic effects of treating patients with medial compartment osteoarthritis ( OA ) of the knee with laterally wedged insoles with subtalar strapping of varying elevations . DESIGN Prospect i ve quasi-experimental evaluation . SETTING Outpatient clinic in Japan . PARTICIPANTS Sixty-two women out patients with knee OA who were r and omized into 3 groups according to their birth date s and wedge elevation . INTERVENTIONS Participants wore laterally wedged insoles with subtalar strapping with elevations of 8 , 12 , or 16 mm for 2 weeks . MAIN OUTCOME MEASURES St and ing radiographs were used to analyze the femorotibial angle for each subject , both with and without their respective unilateral insoles . The remission scores of the Lequesne index of severity for knee OA were compared among the 3 groups at the conclusion . Participants were asked to report adverse effects on use of the insoles . RESULTS The 16-mm group ( n=21 ) showed a significantly greater valgus correction of the femorotibial angle than the 8-mm group ( n=20 ) ( P=.013 ) . The remission score was significantly improved in the 12-mm group ( n=21 ) compared with the 16-mm group ( P=.029 ) . Adverse effects were more common in the 16-mm group ( 9/21 , 42.8 % ) than in the 12-mm ( 3/21 , 14.3 % ) or 8-mm ( 2/20 , 10 % ) groups . CONCLUSIONS The degree of change in femorotibial angle with the insole with subtalar strapping was affected by the tilt of the lateral wedge . For constant routine use , the 8- or 12-mm elevation wedged insoles with subtalar strapping may be more comfortable and effective than the 16-mm elevation wedge 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 To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis ( OA ) of the knee . METHODS Novel lateral wedged insoles with elastic subtalar strapping ( the subtalar strapping support group ) and ankle supporters with a lateral wedged heel insert ( the sock-type ankle support group ) were prepared . Eighty-eight female out patients with knee OA were treated with 1 of the 2 insoles for 8 weeks . Femorotibial angle was assessed by st and ing radiographs with and without unilateral insole use for each subject . Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment . RESULTS Participants wearing the insole with subtalar strapping ( n = 42 ) demonstrated significantly decreased femorotibial angle ( an average of change : -3.1 degrees + /- 2.5 degrees , P < 0.0001 ) , but a significant difference was not found in the sock-type ankle support group ( n = 46 ; -0.4 degrees + /- 1.1 degrees , P > 0.05 ) . In the subtalar strapping support group , pain during bed rest with full extension of the knee ( P < 0.0001 ) , pain after getting up ( P = 0.04 ) , pain on getting up from a seated position ( P = 0.021 ) , maximum distance walked ( P = 0.009 ) , and aggregate severity score ( P < 0.0001 ) were significantly improved compared with baseline . In contrast , significant symptomatic improvement was detected only in the aggregate score ( P = 0.016 ) in the sock-type ankle support group , but not in any of the 10 specific categories . CONCLUSION The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA OBJECTIVE To assess the optimal duration of daily wear for a laterally wedged insole with subtalar strapping in subjects with medial compartment osteoarthritis of the knee ( knee OA ) . DESIGN The setting was an outpatient clinic . Eighty-one patients with knee OA were prospect ively r and omized according to birth date and to either 2 weeks of treatment with a lateral wedge with subtalar strapping for less than 5 h ( the short group ) , 5 - 10 h ( the medium group ) or greater than 10 h ( the long group ) each day , or to treatment with a subtalar strapping b and without lateral wedge ( the placebo group ) . St and ing radiographs were used to analyze the femorotibial angle for each subject , both with and without their respective orthotic device . The remission scores of Lequesne index were compared among the four groups at the conclusion . RESULTS The short ( n=21 ) , medium ( n=20 ) and long ( n=18 ) groups demonstrated a significant greater valgus correction of the femorotibial angle than the placebo group ( n=22 ) ( P<0.0001 ) . The remission score was significantly improved in the medium group compared to the placebo ( P=0.001 ) and long ( P=0.001 ) groups . CONCLUSIONS An optimal duration of insole with subtalar strapping wear for patients with varus deformity knee OA may be between 5 and 10 h each day 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 OBJECTIVE To investigate anthropometric measures that closely correlate with symptomatic relief of osteoarthritis ( OA ) of the knee in response to lateral wedged insole use . METHODS Seventy-one patients with medial compartment knee OA were treated with insoles with subtalar strapping or insoles with talonavicular strapping . R and omization was performed according to birth date . The following variables were evaluated : age , disease duration , Kellgren-Lawrence radiographic stage , body mass index , percent body fat , waist to hip ratio , lower extremity lean body mass ( L-LBM ) per body weight , and radiographic femorotibial angle at baseline . The trial lasted 8 weeks . The correlation between each variable and the remission score ( delta score ) using the Lequesne index of severity was analyzed . RESULTS In the subtalar strapping group ( n = 34 ) , delta score of knee OA was more strongly associated with age ( p = 0.004 , r = 0.48 ) than other variables . A significant correlation was also observed between L-LBM per body weight and delta score ( p = 0.041 , r = -0.36 ) in the subtalar strapping group . No other variables significantly correlated with the delta score in the subtalar strapping groups . No variable significantly correlated with the ? score in the talonavicular strapping group ( n = 37 ) . CONCLUSION We previously reported that use of insoles with subtalar strapping leads to valgus realignment of the femorotibial angle in patients with knee OA with varus deformity , and it may have a similar therapeutic effect to that of high tibial osteotomy . These data suggest that the insole with subtalar strapping is more efficacious for younger patients and those with a higher L-LBM per body weight , and less efficacious for older patients with sarcopenia OBJECTIVE To assess the effect of a lateral-wedge insole with elastic strapping of the subtalar joint on the femorotibial angle in patients with varus deformity of the knee . METHODS The efficacy of a wedged insole with subtalar straps and that of a traditional wedged insole shoe insert were compared . Sixty-six female out patients with knee osteoarthritis ( OA ) were r and omized ( according to birth date ) to be treated with either the strapped or the traditional inserted insole . St and ing radiographs with unilateral insole use were used to analyze the femorotibial angles for each patient . In both groups , the baseline and 6-month visual analog scale ( VAS ) scores for subjective knee pain and the Lequesne index scores for knee OA were compared . RESULTS The 61 patients who completed the 6-month study were evaluated . At baseline , there was no significant difference in the femorotibial angle ( P = 0.66 ) and the VAS score ( P = 0.75 ) between the 2 groups . At the 6-month assessment , the 29 subjects wearing the subtalar-strapped insole demonstrated a significantly decreased femorotibial angle ( P < 0.0001 ) and significantly improved VAS scores ( P = 0.001 ) and Lequesne index scores ( P = 0.033 ) compared with their baseline assessment s. These significant differences were not observed in the 32 subjects assigned to the traditional shoe-inserted wedged insole . CONCLUSION These results suggest that an insole with a subtalar strap maintained the valgus correction of the femorotibial angle in patients with varus knee OA for 6 months , indicating longer-term clinical improvement with the strapped insert compared with the traditional insert OBJECTIVES To document adherence to two parts of the EULAR 2000 recommendations for knee osteoarthritis , concerning non-pharmacological and pharmacological first line management ; and to identify factors influencing adherence to the recommendations . METHODS In a prospect i ve study , 1030 r and omly selected French general practitioners completed question naires about three unselected out patients with osteoarthritis , and about their own practice , knowledge , and agreement with the EULAR 2000 recommendations . Percentages of adherence of their prescriptions to both parts of the recommendation were calculated , and probabilities of non-adherence analysed in relation to patient and physician related characteristics , using multilevel logistic regression analysis . RESULTS Data were obtained from 967 physicians and 2430 patients . The EULAR 2000 recommendations were familiar to 79 % of the GPs ; 99 % agreed with the non-pharmacological part and 97 % with the pharmacological part . Adherence to the two parts was 74.8 % and 73.6 % , but 54.2 % for both together . Factors increasing adherence to the non-pharmacological recommendation were patient body mass index > 35 kg/m(2 ) ( odds ratio 0.11 ( 95 % confidence interval , 0.06 to 0.21 ) ) , patient 's stated preference for a treatment ( OR 0.43 ( 0.55 to 0.97 ) ) , and physician 's regular continuance of medical education ( OR 0.76 ( 0.59 to 0.98 ) ) ; patient 's age and duration of symptoms decreased adherence . Factors increasing adherence to the pharmacological recommendation were gastrointestinal disease ( OR 0.50 ( 0.35 to 0.72 ) ) and physician 's knowledge of the EULAR recommendations ( OR 0.75 ( 0.60 to 0.93 ) ) . CONCLUSIONS Although most physicians agreed with the EULAR 2000 recommendations , adherence was only approximately 75 % for each of the non-pharmacological and pharmacological recommendations and 54 % for both together OBJECTIVE Gait biomechanics ( knee adduction moment , center of pressure ) and static alignment were investigated to determine the mechanical effect of foot orthoses in people with medial compartment knee osteoarthritis . DESIGN Repeated measures design in which subjects were exposed to three conditions ( normal footwear , heel wedge and orthosis ) in r and om order . BACKGROUND The knee adduction moment is an indirect measure of medial compartment loading . It was hypothesized that the use of a 5 degrees valgus wedge and 5 degrees valgus modified orthosis would shift the center of pressure laterally during walking , thereby decreasing the adduction moment arm and the adduction moment . METHODS Peak knee adduction moment and center of pressure excursion were obtained in nine subjects with medial compartment knee OA during level walking using an optoelectric system and force plate . Static radiographs were taken in 12 subjects using precision radiographs . RESULTS There was no difference between conditions in static alignment , the peak adduction moment or excursion of the center of pressure in the medial-lateral direction . No relationship was found between the adduction moment and center of pressure excursion in the medial-lateral plane . The displacement of the center of pressure in the anterior-posterior direction , measured relative to the laboratory coordinate system , was decreased with the orthosis compared to the control condition ( P=0.036 ) and this measure was correlated with the adduction moment ( r=0.45 , P=0.019 ) . CONCLUSIONS The proposed mechanism was not supported by the findings . The reduction in the center of pressure excursion in the anterior-posterior direction suggests that foot positioning was altered , possibly to a toe-out position , while subjects wore the orthoses . Based on the current findings , we hypothesize that toe-out positioning may reduce medial joint load . RELEVANCE Knee Osteoarthritis is the most common cause of chronic disability amongst seniors . Developing inexpensive , non-invasive treatment strategies for this large population has potential to impact health care costs , quality of life and clinical outcomes OBJECTIVE To assess the efficacy of a lateral wedge insole with elastic strapping of the subtalar joint for conservative treatment of osteoarthritis ( OA ) of the knee . METHODS The efficacy of a novel insole with elastic subtalar strapping and a traditional shoe insert wedge insole was compared . Ninety female out patients with OA of the knee were treated with wedge insoles for 8 weeks . R and omization was performed according to birth date . St and ing radiographs with unilateral insole use were used to analyze the femorotibial and talar tilt angles for each patient with and without their respective insole . Visual analog scale ( VAS ) score for subjective knee pain at the final assessment was compared with that at baseline in both groups . RESULTS Participants wearing the elastically strapped insole ( n = 46 ) had significantly decreased femorotibial angle ( p < 0.0001 ) and talar tilt angle ( p = 0.005 ) and significantly improved VAS pain score ( p = 0.045 ) in comparison with baseline assessment s. These significant differences were not found in the group with the inserted insole ( n = 44 ) . CONCLUSION The novel strapped insole leads to valgus angulation of the talus , result ing in correction of the femorotibial angle in patients with knee OA with varus deformity , and may have a therapeutic effect similar to that of high tibial osteotomy |
11,182 | 23,538,175 | We hope that the ISPOR CHEERS statement and the accompanying task force report guidance will lead to more consistent and transparent reporting , and ultimately , better health decisions . | BACKGROUND Economic evaluations of health interventions pose a particular challenge for reporting because substantial information must be conveyed to allow scrutiny of study findings .
Despite a growth in published reports , existing reporting guidelines are not widely adopted .
There is also a need to consoli date and up date existing guidelines and promote their use in a user-friendly manner .
A checklist is one way to help authors , editors , and peer review ers use guidelines to improve reporting .
OBJECTIVE The task force 's overall goal was to provide recommendations to optimize the reporting of health economic evaluations .
The Consoli date d Health Economic Evaluation Reporting St and ards ( CHEERS ) statement is an attempt to consoli date and up date previous health economic evaluation guidelines into one current , useful reporting guidance .
The primary audiences for the CHEERS statement are research ers reporting economic evaluations and the editors and peer review ers assessing them for publication . | Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled OBJECTIVE To assess and compare the quality of nonstructured and structured abstract s of original research articles in three medical journals . DESIGN Blind , criterion-based observational study . SAMPLE R and om sample of 300 abstract s ( 25 abstract s per journal each year ) of articles published in the British Medical Journal ( BMJ ) , the Canadian Medical Association Journal and the Journal of the American Medical Association ( JAMA ) in 1988 and 1989 ( nonstructured abstract s ) and in 1991 and 1992 ( structured abstract s ) . MAIN OUTCOME MEASURES The quality of abstract s was measured against 33 objective criteria , which were divided into eight categories ( purpose , research design , setting , subjects , intervention , measurement of variables , results and conclusions ) . The quality score was determined by dividing the number of criteria present by the number applicable ; the score varied from 0 to 1 . RESULTS The overall mean quality scores for nonstructured and structured abstract s were 0.57 and 0.74 respectively ( p < 0.001 ) . The frequency in meeting the specific criteria was generally higher for the structured abstract s than for the nonstructured ones . The mean quality score was higher for nonstructured abstract s in JAMA than for those in BMJ ( 0.60 v. 0.54 , p < 0.05 ) . The scores for structured abstract s did not differ significantly between the three journals . CONCLUSIONS The findings support recommendations that promote the use of structured abstract s. Further studies should be performed to assess the effect of time on the quality of abstract s and the extent to which abstract s reflect the content of the articles Abstract Objective To compare the distribution of P values in abstract s of r and omised controlled trials with that in observational studies , and to check P values between 0.04 and 0.06 . Design Cross sectional study of all 260 abstract s in PubMed of articles published in 2003 that contained “ relative risk ” or “ odds ratio ” and reported results from a r and omised trial , and r and om sample s of 130 abstract s from cohort studies and 130 from case-control studies . P values were noted or calculated if unreported . Main outcome measures Prevalence of significant P values in abstract s and distribution of P values between 0.04 and 0.06 . Results The first result in the abstract was statistically significant in 70 % of the trials , 84 % of cohort studies , and 84 % of case-control studies . Although many of these results were derived from subgroup or secondary analyses , or biased selection of results , they were presented without reservations in 98 % of the trials . P values were more extreme in observational studies ( P < 0.001 ) and in cohort studies than in case-control studies ( P = 0.04 ) . The distribution of P values around P = 0.05 was extremely skewed . Only five trials had 0.05 ≤ P < 0.06 , whereas 29 trials had 0.04 ≤ P < 0.05 . I could check the calculations for 27 of these trials . One of four non-significant results was significant . Four of the 23 significant results were wrong , five were doubtful , and four could be discussed . Nine cohort studies and eight case-control studies reported P values between 0.04 and 0.06 , but in all 17 cases P < 0.05 . Because the analyses had been adjusted for confounders , these results could not be checked . Conclusions Significant results in abstract s are common but should generally be disbelieved CONTEXT The section of a research article most likely to be read is the abstract , and therefore it is particularly important that the abstract reflect the article faithfully . OBJECTIVE To assess abstract s accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself . DESIGN Analysis of simple r and om sample s of 44 articles and their accompanying abstract s published during 1 year(July 1 , 1996-June 30 , 1997 ) in each of 5 major general medical journals ( Annals of Internal Medicine , BMJ , JAMA , Lancet , and New Engl and Journal of Medicine ) and a consecutive sample of 44 articles published during 15 months ( July 1 , 1996-August 15 , 1997 ) in the CMAJ . MAIN OUTCOME MEASURE Abstract s were considered deficient if they contained data that were either inconsistent with corresponding data in the article 's body ( including tables and figures ) or not found in the body at all . RESULTS The proportion of deficient abstract s varied widely ( 18%-68 % ) and to a statistically significant degree ( P<.001 ) among the 6 journals studied . CONCLUSIONS Data in the abstract that are inconsistent with or absent from the article 's body are common , even in large-circulation general medical journals Objectives To evaluate the cost effectiveness of 40 mg simvastatin daily continued for life in people of different ages with differing risks of vascular disease . Design A model developed from a r and omised trial was used to estimate lifetime risks of vascular events and costs of treatment and hospital admissions in the United Kingdom . Setting 69 hospitals in the UK . Participants 20 536 men and women ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes . Interventions 40 mg simvastatin daily versus placebo for an average of 5 years . Main outcome measures Cost effectiveness of 40 mg simvastatin daily expressed as additional cost per life year gained . Major vascular event defined as non-fatal myocardial infa rct ion or death from coronary disease , any stroke , or revascularisation procedure . Results were extrapolated to younger and older age groups at lower risk of vascular disease than were studied directly , as well as to lifetime treatment . Results At the April 2005 UK price of � 4.87 ( € 7 ; $ 9 ) per 28 day pack of generic 40 mg simvastatin , lifetime treatment was cost saving in most age groups and vascular disease risk groups studied directly . Gains in life expectancy and cost savings decreased with increasing age and with decreasing risk of vascular disease . People aged 40 - 49 with 5 year risks of major vascular events of 42 % and 12 % at start of treatment gained 2.49 and 1.67 life years , respectively . Treatment with statins remained cost saving or cost less than � 2500 per life year gained in people as young as 35 years or as old as 85 with 5 year risks of a major vascular event as low as 5 % at the start of treatment . Conclusions Treatment with statins is cost effective in a wider population than is routinely treated at present BACKGROUND Baseline data collected on each patient at r and omisation in controlled clinical trials can be used to describe the population of patients , to assess comparability of treatment groups , to achieve balanced r and omisation , to adjust treatment comparisons for prognostic factors , and to undertake subgroup analyses . We assessed the extent and quality of such practice s in major clinical trial reports . METHODS A sample of 50 consecutive clinical -trial reports was obtained from four major medical journals during July to September , 1997 . We tabulated the detailed information on uses of baseline data by use of a st and ard form . FINDINGS Most trials presented baseline comparability in a table . These tables were often unduly large , and about half the trials inappropriately used significance tests for baseline comparison . Methods of r and omisation , including possible stratification , were often poorly described . There was little consistency over whether to use covariate adjustment and the criteria for selecting baseline factors for which to adjust were often unclear . Most trials emphasised the simple unadjusted results and covariate adjustment usually made negligible difference . Two-thirds of the reports presented subgroup findings , but mostly without appropriate statistical tests for interaction . Many reports put too much emphasis on subgroup analyses that commonly lacked statistical power . INTERPRETATION Clinical trials need a predefined statistical analysis plan for uses of baseline data , especially covariate-adjusted analyses and subgroup analyses . Investigators and journals need to adopt improved st and ards of statistical reporting , and exercise caution when drawing conclusions from subgroup findings Background Recent r and omised trials have demonstrated a statistically significant effect of trastuzumab on disease-free survival when used as adjuvant therapy for human epidermal growth factor receptor 2 protein (HER2)-positive resectable early stage breast cancer , with a treatment course lasting either 9 or 52 weeks . However , the cost effectiveness of adjuvant trastuzumab with respect to mortality remains uncertain , especially in an Australian setting . Objective To estimate the cost effectiveness of trastuzumab in Australia , in a cohort of 50-year-old patients with HER2-positive breast cancer over a lifetime , using ( i ) disease-free survival and cardiotoxicity data from recent r and omised trials ; ( ii ) information on long-term survival of patients with treated primary breast cancer ; and ( iii ) costs of treating local and distant relapses and disease from causes other than breast cancer . Methods A Markov model consisting of four health states ( remission , loco-regional recurrence , metastatic disease and death ) was developed . Transition probabilities corresponded to patterns of relapse and metastases seen in recent trials . The model was run until age 100 years to allow calculation of average survival . Outcome measures were life-years and QALYs ( calculated using utility weights reported in the literature ) .The model was calibrated to reflect literature evidence that the risk of breast cancer recurrence following primary treatment diminishes progressively to zero after about 20 years . It was assumed that the morbidity benefit of trastuzumab observed in trials would be present for 5 years but would then diminish progressively to zero after 8 years . Costs ( year 2005 values ) and benefits were discounted at 3 % per annum . Results For every 1000 patients treated with a 52-week course of trastuzumab , there were 136 fewer breast cancer deaths ( relative risk reduction 28 % ) . The incremental cost-effectiveness ratios ( ICERs ) were Australian dollars ($A)13 730 per year of life saved ( YOLS ) and $ A22 793 per QALY . The net incremental cost was $ A56.3 million ( $ A414 012/cancer death avoided ) . Cost effectiveness declined ( ICER = $ A27 734/QALY ) in older patients ( age 65 years at treatment initiation).The ICER was driven mainly by the drug acquisition costs , the assumption of the duration of benefit and the discount rate . Cost offsets from reduced costs of treating recurrent or metastatic breast cancer during follow-up were present but these factors were of less importance according to sensitivity analyses . The 9-week treatment schedule approached economic dominance ( ICER = $ A1700/QALY ) because of decreased costs , improved relative risk for prevention of metastases and more cancer deaths avoided ( 196 ) . Conclusion The results suggest that trastuzumab as adjuvant therapy for early breast cancer may be cost effective when given over either 52 or 9 weeks at current acquisition costs in Australia . However , the overall budget impact of the 52-week course is significant , and the 9-week course appears economically attractive The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . 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 . Background Several r and omized controlled trials have confirmed the usefulness of trastuzumab as an adjuvant therapy for HER2-overexpressed breast cancer patients ; however , the costs for 1-year treatment are high . Therefore , we performed an economic analysis regarding the efficient distribution of medical re sources . Methods To analyze the cost-effectiveness for a 1-year adjuvant trastuzumab treatment group compared with the observation group , we constructed a Markov model adopting a 3 % per year discount rate for costs and outcomes . The time horizon was 50 years . The perspective was that of health-care payers , as only direct medical costs were calculated . The outcome was measured as life-year gained ( LYG ) from 2-year follow-up HERA trial data . Results The ICER of the st and ard setting ( 5 years efficacy and 50–60 kg patient weight ) was JPY 2,600,000 ( € 17,000 ) per LYG . The calculation results of other weight class ICER were JPY 2,200,000 ( € 15,000 ) and JPY 3,300,000 ( € 22,000 ) per LYG for the patients , respectively , who weighed less than 50 kg , and 60–75 kg . In the sensitivity analysis , the period of trastuzumab efficacy was the most influential parameter for the result of cost-effectiveness . However , even if the trastuzumab efficacy were to continue for only 2 years , at least , which is a conservative setting judging from the joint analysis ( NSABP B-31 and NCCTG N9831 trials ) , the ICER remains acceptable for any weight class . Conclusion These results suggest that the 1-year adjuvant trastuzumab treatment is cost-effective . Both clinical and economic benefits were superior for the 1-year adjuvant trastuzumab treatment group compared with the observation group BACKGROUND Before the introduction of the immunomodulatory therapies for multiple sclerosis ( MS ) , treatment options for MS consisted of symptomatic management ( physical therapy and pharmacological treatment for symptom management ) . Symptomatic management for MS has been supplemented in the past decade by 2 new classes of immunomodulatory therapies that have been approved as first-line treatments for relapsing-remitting multiple sclerosis ( RRMS ) : subcutaneous glatiramer acetate ( SC GA ) and 3 beta-interferons : intramuscular interferon beta-1a ( IM IFNbeta-1a ) , SC IFNbeta-1a , and SC IFNbeta-1b . OBJECTIVE To estimate the economic outcomes of 5 treatment strategies : symptom management alone , symptom management combined with SC GA , IM IFNbeta1-a , SC IFNbeta1-a , or SC IFNbeta1-b in patients diagnosed with RRMS . METHODS A literature -based Markov model was developed to assess the cost-effectiveness of 5 treatment strategies for managing a hypothetical cohort of patients diagnosed with RRMS in the United States--4 immunomodulatory drug therapies and symptom management alone . Health states were based on the Kurtzke Exp and ed Disability Status Scale ( EDSS ) , a widely accepted scale for assessing RRMS ( higher EDSS scores = increased disease severity ) . Baseline relapse and disease progression transition probabilities for symptom management were obtained from natural history studies . Treatment effects of the immunomodulatory therapies were estimated by applying a percentage reduction to the symptom management transition probabilities for relapse ( 27 % reduction ) and disease progression ( 30 % reduction ) . Transition probabilities were subsequently adjusted to account for ( 1 ) the effects of neutralizing antibodies , specifically on relapse rates by assuming no additional therapy benefits after the second year of continuous therapy , and ( 2 ) treatment discontinuation . Therapy-specific data were obtained from clinical trials and long-term follow-up observational studies . Transitions among health states occurred in 1-month cycles for the lifetime of a patient . Costs ( 2005 US$ ) and outcomes were discounted at 3 % annually . RESULTS The incremental cost per quality -adjusted life-year for the 4 immunomodulatory therapies is $ 258,465 , $ 303,968 , $ 416,301 , and $ 310,691 for SC GA , IM IFNbeta-1a , SC IFNbeta-1a , and SC IFNbeta-1b , respectively , compared with symptom management alone . Sensitivity analyses demonstrated that results were sensitive to changes in utilities , disease progression rates , time horizon , and immunomodulatory therapy cost . CONCLUSIONS The pharmacoeconomic model determined that SC GA was the best strategy of the 4 immunomodulatory therapies used to manage MS and result ed in better outcomes than symptom management alone . Sensitivity analyses indicated that the model was sensitive to changes in a number of key parameters , and thus changes in these key parameters would likely influence the estimated cost-effectiveness results . Head-to-head r and omized clinical trials comparing the immunomodulatory therapies for the treatment of MS are necessary to vali date the projections from the pharmacoeconomic analyses , particularly since the results available today from the clinical trials do not account adequately for treatment dropouts Abstract Objective To determine whether , from a health provider and patient perspective , surgical stabilisation of the spine is cost effective when compared with an intensive programme of rehabilitation in patients with chronic low back pain . Design Economic evaluation alongside a pragmatic r and omised controlled trial . Setting Secondary care . Participants 349 patients r and omised to surgery ( n = 176 ) or to an intensive rehabilitation programme ( n = 173 ) from 15 centres across the United Kingdom between June 1996 and February 2002 . Main outcome measures Costs related to back pain and incurred by the NHS and patients up to 24 months after r and omisation . Return to paid employment and total hours worked . Patient utility as estimated by using the EuroQol EQ-5D question naire at several time points and used to calculate quality adjusted life years ( QALYs ) . Cost effectiveness was expressed as an incremental cost per QALY . Results At two years , 38 patients r and omised to rehabilitation had received rehabilitation and surgery whereas just seven surgery patients had received both treatments . The mean total cost per patient was estimated to be £ 7830 ( SD £ 5202 ) in the surgery group and £ 4526 ( SD £ 4155 ) in the intensive rehabilitation arm , a significant difference of £ 3304 ( 95 % confidence interval £ 2317 to £ 4291 ) . Mean QALYs over the trial period were 1.004 ( SD 0.405 ) in the surgery group and 0.936 ( SD 0.431 ) in the intensive rehabilitation group , giving a non-significant difference of 0.068 ( –0.020 to 0.156 ) . The incremental cost effectiveness ratio was estimated to be £ 48 588 per QALY gained ( –£279 883 to £ 372 406 ) . Conclusion Two year follow-up data show that surgical stabilisation of the spine may not be a cost effective use of scarce healthcare re sources . However , sensitivity analyses show that this could change — for example , if the proportion of rehabilitation patients requiring subsequent surgery continues to increase Background Some patients will experience more or less benefit from treatment than the averages reported from clinical trials ; such variation in therapeutic outcome is termed heterogeneity of treatment effects ( HTE ) . Identifying HTE is necessary to individualize treatment . The degree to which heterogeneity is sought and analyzed correctly in the general medical literature is unknown . We undertook this literature sample to track the use of HTE analyses over time , examine the appropriateness of the statistical methods used , and explore the predictors of such analyses . Methods Articles were selected through a probability sample of r and omized controlled trials ( RCTs ) published in Annals of Internal Medicine , BMJ , JAMA , The Lancet , and NEJM during odd numbered months of 1994 , 1999 , and 2004 . RCTs were independently review ed and coded by two abstract ors , with adjudication by a third . Studies were classified as reporting : ( 1 ) HTE analysis , utilizing a formal test for heterogeneity or treatment-by-covariate interaction , ( 2 ) subgroup analysis only , involving no formal test for heterogeneity or interaction ; or ( 3 ) neither . Chi-square tests and multiple logistic regression were used to identify variables associated with HTE reporting . Results 319 studies were included . Ninety-two ( 29 % ) reported HTE analysis ; another 88 ( 28 % ) reported subgroup analysis only , without examining HTE formally . Major covariates examined included individual risk factors associated with prognosis , responsiveness to treatment , or vulnerability to adverse effects of treatment ( 56 % ) ; gender ( 30 % ) ; age ( 29 % ) ; study site or center ( 29 % ) ; and race/ethnicity ( 7 % ) . Journal of publication and sample size were significant independent predictors of HTE analysis ( p < 0.05 and p < 0.001 , respectively ) . Conclusion HTE is frequently ignored or incorrectly analyzed . An iterative process of exploratory analysis followed by confirmatory HTE analysis will generate the data needed to facilitate an individualized approach to evidence -based medicine PURPOSE One-year adjuvant trastuzumab ( AT ) therapy , with or without anthracyclines , increases disease-free and overall survival in early-stage HER2/neu-positive breast cancer . We sought to evaluate the cost effectiveness of these regimens , which are expensive and potentially toxic . METHODS We used a Markov health-state transition model to simulate three adjuvant therapy options for a cohort of 49-year-old women with HER2/neu-positive early-stage breast cancer : conventional chemotherapy without trastuzumab ; anthracycline-based AT regimens used in the National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831 trials ; and the nonanthracycline AT regimen used in the Breast Cancer International Research group 006 trial . The base case used treatment efficacy measures reported in the r and omized clinical trials of AT . We measured health outcomes in quality -adjusted life-years ( QALYs ) and costs in 2005 United States dollars ( US dollars ) and subjected results to probabilistic sensitivity analysis . RESULTS In the base case , the anthracycline-based AT arm has an incremental cost-effectiveness ratio ( ICER ) of 39,982 dollars/QALY , whereas the nonanthracycline AT arm is more expensive and less effective ; this result is insensitive to changes in recurrence rates , but if there is no benefit after 4 years , ICERs exceed 100,000 dollars/QALY for both AT arms . Results are moderately sensitive to variation in breast cancer survival rates and trastuzumab cost , and less sensitive to variations in cardiac toxicity . CONCLUSION AT has an ICER comparable to those for other widely used interventions . Longer clinical follow-up is warranted to evaluate the long-term efficacy and toxicity of different AT regimens BACKGROUND A short saphenous vein segment is commonly used as a conduit for coronary artery bypass grafting , and clinicians must decide whether to obtain it by performing open ( OVH ) or endoscopic vein harvest ( EVH ) . We conducted a health economic evaluation , using data on re source usage collected alongside a r and omized controlled trial , to investigate whether EVH is cost-effective compared with OVH . METHODS Analyses were performed in accordance with international guidelines for health economic evaluations . We constructed 3 cost-levels as the current literature is inconclusive as to which re source consumptions differ significantly between harvesting methods . Outcomes were measured as purulent infections avoided in the cost-effectiveness analysis and for the cost-utility analysis we estimated quality -adjusted life-years gained . Results were presented as incremental cost-effectiveness ratios : ie , the extra cost of obtaining one extra quality -adjusted life-year and the extra cost of avoiding one purulent infection . To h and le uncertainties , we performed bias corrected bootstrap analyses on 5,000 re sample s and constructed cost-effectiveness acceptability curves . RESULTS The incremental cost-effectiveness ratio was $ 79,391/ quality -adjusted life-year and $ 1,970/purulent infection avoided when costs and outcomes within 35 days postoperatively were compared . Within 35 days postoperatively , EVH was less than 1 % cost-effective at a willingness-to-pay threshold of $ 50,000/ quality -adjusted life-year . CONCLUSIONS The EVH was not cost-effective within 35 days postoperatively . Future studies should investigate long-term cost effectiveness Models for the economic evaluation of health technologies provide valuable information to decision makers . The choice of model structure is rarely discussed in published studies and can affect the results produced . Many papers describe good modelling practice , but few describe how to choose from the many types of available models . This paper develops a new taxonomy of model structures . The horizontal axis of the taxonomy describes assumptions about the role of expected values , r and omness , the heterogeneity of entities , and the degree of non-Markovian structure . Commonly used aggregate models , including decision trees and Markov models require large population numbers , homogeneous sub-groups and linear interactions . Individual models are more flexible , but may require replications with different r and om numbers to estimate expected values . The vertical axis of the taxonomy describes potential interactions between the individual actors , as well as how the interactions occur through time . Models using interactions , such as system dynamics , some Markov models , and discrete event simulation are fairly uncommon in the health economics but are necessary for modelling infectious diseases and systems with constrained re sources . The paper provides guidance for choosing a model , based on key requirements , including output requirements , the population size , and system complexity Abstract This article provides an empirically supported reminder of the importance of accuracy in scientific communication . The authors identify common types of inaccuracies in research abstract s and offer suggestions to improve abstract -article agreement . Abstract s accompanying 13 % of a r and om sample of 400 research articles published in 8 American Psychological Association journals during 1997 and 1998 contained data or cl aims inconsistent with or missing from the body of the article . Error rates ranged from 8 % to 18 % , although between-journal differences were not significant . Many errors ( 63 % ) were unlikely to cause substantive misinterpretations . Unfortunately , 37 % of errors found could be seriously misleading with respect to the data or cl aims presented in the associated article . Although deficient abstract s may be less common in psychology journals than in major medical journals ( R. M. Pitkin , M. A. Branagan , & L. F. Burmeister , 1999 ) , there is still cause for concern and need for improvement BACKGROUND Past observational studies of the R AND /UCLA Appropriateness Method have shown that the composition of panels affects the ratings that are obtained . Panels of mixed physicians make different judgments from panels of single specialty physicians , and physicians who use a procedure are more likely to rate it more highly than those who do not . OBJECTIVES To determine the effect of using physicians and health care managers within a panel design ed to assess quality indicators for primary care and to test the effect of different types of feedback within the panel process . METHOD A two-round postal Delphi survey of health care managers and family physicians rated 240 potential indicators of quality of primary care in the United Kingdom to determine their face validity . Following round one , equal numbers of managers and physicians were r and omly allocated to receive either collective ( whole sample ) or group-only ( own professional group only ) feedback , thus , creating four subgroups of two single-specialty panels and two mixed panels . RESULTS Overall , managers rated the indicators significantly higher than physicians . Second-round scores were moderated by the type of feedback received with those receiving collective feedback influenced by the other professional group . CONCLUSIONS This paper provides further experimental evidence that consensus panel judgments are influenced both by panel composition and by the type of feedback which is given to participants during the panel process . Careful attention must be given to the methods used to conduct consensus panel studies , and methods need to be described in detail when such studies are reported BACKGROUND The efficacy of sequential adjuvant trastuzumab ( aTZ ) after chemotherapy in women with early-stage human epidermal growth factor-2 (HER2/neu)-positive breast cancer reported by the up date d Herceptin Adjuvant ( HERA ) trial appears less favorable than originally reported . Based on these up date d results , we estimated the cost-utility ( CU ) of sequential aTZ relative to chemotherapy alone in terms of incremental cost per quality -adjusted life-year ( QALY ) gained . METHODS A Markov model estimated incremental costs and outcomes of 12 months of aTZ after adjuvant chemotherapy in women with HER2/neu-positive breast cancer over a 25-year horizon . The model incorporated four broad health states ( disease-free , local recurrence [ LCR ] , distant recurrence [ DCR ] , death ) , stratified with or without symptomatic cardiotoxicity . Baseline event rates and 3-year relative risk ( RR = 0.75 ) were derived from the HERA trial . As the duration of the benefit remains uncertain , the analysis considered 5-year and 3-year duration of benefit in two scenarios . Costs and utility weights were from the literature . The analysis took a direct payer perspective , with costs reported in 2007 Canadian dollars . Costs and QALYs were discounted by 3 % annually . RESULTS The mean CU of sequential aTZ at a 25-year horizon was $ 72,292 per QALY gained in the 5-year scenario and $ 127,862 per QALY gained in the 3-year scenario . Results were particularly sensitive to the magnitude and duration of carryover benefit . CONCLUSIONS The CU of sequential aTZ is primarily dependent on the magnitude and duration of benefit . Further clinical research is required to establish the optimum sequence and duration of aTZ therapy and clarify the magnitude and duration of treatment benefit OBJECTIVES To estimate the cost-effectiveness of topical intranasal steroids for the treatment of otitis media with effusion ( OME ) in primary care from the perspective of the UK National Health Service . METHODS An economic evaluation was conducted based on evidence from the double-blind , r and omized , placebo-controlled GPRF [ General Practice Research Framework ] Nasal Steroids for Otitis Media with Effusion ( GNOME ) trial . Participants comprised 217 children aged 4 - 11 years who had at least one episode of otitis media or related ear problem in the previous 12 months and had tympanometrically confirmed bilateral OME . Children were r and omly allocated to receive either mometasone furoate 50 microg or placebo spray once daily into each nostril for 3 months . The main outcome measure was the incremental cost per quality -adjusted life-year ( QALY ) gained for topical steroids compared with placebo . The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative willingness to pay thresholds . RESULTS Children receiving topical steroids accrued nonsignificantly higher costs ( incremental cost/child : pound11 , 95 % confidence interval [ CI ] : - pound199 to pound222 ) and nonsignificantly fewer QALYs ( incremental QALY gain/child : -0.0166 , 95 % CI : -0.0652 to 0.0320 ) than those receiving placebo . Topical steroids had a 24.19 % probability of being cost-effective at a pound20,000 per QALY gained threshold , a 23.82 % probability of being more effective and a 46.25 % probability of being less costly . Sensitivity and subgroup analyses showed incremental costs and benefits to be highly sensitive to the methods used and the patient group considered , although differences between groups did not reach statistical significance in any analysis . CONCLUSIONS Topical steroids are unlikely to be a cost-effective treatment for OME in general practice BACKGROUND Treatment decisions in clinical cardiology are directed by results from r and omized clinical trials ( RCTs ) . We studied the appropriateness of the use and interpretation of subgroup analysis in current therapeutic cardiovascular RCTs . METHODS We review ed main reports of phase 3 cardiovascular RCTs with at least 100 patients , published in 2002 and 2004 , and from major journals ( Circulation , J Am Coll Cardiol , Am Heart J , Am J Cardiol , N Engl J Med , Lancet , JAMA , BMJ , Ann Intern Med ) . Information on subgroups included prespecification , number , interaction test use , significant subgroups found , and emphasis on findings . We examined appropriateness of reporting and differences according to sample size , overall trial result , and CONSORT adoption . RESULTS We selected 63 RCTs , with a median of 496 ( range 100 - 15,245 ) patients . Thirty-nine RCTs were reported with subgroup analyses and 26 with > 5 subgroups . No trial was specifically powered to detect subgroup effects , and only 14 RCTs were reported with fully prespecified subgroups . Only 11 RCTs were reported with interaction tests . Furthermore , 21 RCTs were reported with cl aims of significant subgroups and 15 with equal or more emphasis to subgroups than to the overall results . Subgroup analyses in large RCTs ( > 500 patients ) were reported more often than in small ones ( 24/30 vs 15/33 , P = .005 ) . No differences were found according to overall result ( positive/negative ) or CONSORT adoption . CONCLUSIONS Subgroup analyses in recent cardiovascular RCTs were reported with several shortcomings , including a lack of prespecification and testing of a large number of subgroups without the use of the statistically appropriate test for interaction . Reporting of subgroup analysis needs to be substantially improved because emphasis on these secondary results may mislead treatment decisions The r and omised controlled trial ( RCT ) has developed a central role in applied cost-effectiveness studies in health care as the vehicle for analysis . This paper considers the role of trial-based economic evaluation in this era of explicit decision making . It is argued that any framework for economic analysis can only be judged insofar as it can inform two key decisions and be consistent with the objectives of a health care system subject to its re source constraints . The two decisions are , firstly , whether to adopt a health technology given existing evidence and , secondly , an assessment of whether more evidence is required to support this decision in the future . It is argued that a framework of economic analysis is needed which can estimate costs and effects , based on all the available evidence , relating to the full range of possible alternative interventions and clinical strategies , over an appropriate time horizon and for specific patient groups . It must also enable the accumulated evidence to be synthesis ed in an explicit and transparent way in order to fully represent the decision uncertainty . These requirements suggest that , in most circumstances , the use of a single RCT as a vehicle for economic analysis will be an inadequate and partial basis for decision making . It is argued that RCT evidence , with or without economic content , should be viewed as simply one of the sources of evidence , which must be placed in a broader framework of evidence synthesis and decision analysis OBJECTIVES To explore the cost-effectiveness of fluticasone propionate ( FP ) for the treatment of chronic obstructive pulmonary disease ( COPD ) , we estimated costs and quality -adjusted life-years ( QALYs ) over 3 years , based on an economic appraisal of a previously reported clinical trial ( Inhaled Steroids in Obstructive Lung Disease in Europe [ ISOLDE ] ) . METHODS Seven hundred forty-two patients enrolled in the ISOLDE trial who received either FP or placebo had data available on health-care costs and quality of life over the period of the study . The SF-36-based utility scores for quality of life were used to calculate QALYs . A combined imputation and bootstrapping procedure was employed to h and le missing data and to estimate statistical uncertainty in the estimated cumulative costs and QALYs over the study period . The imputation approach was based on propensity scoring and nesting this approach within the bootstrap ensured that multiple imputations were performed such that statistical estimates included imputation uncertainty . RESULTS Complete data were available on mortality within the follow-up period of the study and a nonsignificant trend toward improved survival of 0.06 ( 95 % confidence interval [CI]-0.01 to 0.15 ) life-years was observed . In an analysis based on a propensity scoring approach to missing data we estimated the incremental costs of FP versus placebo to be 1021 sterling pound(95 % CI 619 - 1338 sterling pound ) with an additional effect of 0.11 QALYs ( CI 0.04 - 0.20 ) . Cost-effectiveness estimates for the within-trial period of 17,700 sterling pound per life-year gained ( 6900 sterling pound to infinity ) and 9500 sterling pound per QALY gained ( CI 4300 - 26,500 sterling pound ) were generated that include uncertainty due to the imputation process . An alternative imputation approach did not material ly affect these estimates . CONCLUSIONS Previous analyses of the ISOLDE study showed significant improvement on disease-specific health status measures and a trend toward a survival advantage for treatment with FP . This analysis shows that joint considerations of quality of life and survival result in a substantial increase in QALYs favoring treatment with FP . Based on these data , the inhaled corticosteroid FP appears cost-effective for the treatment of COPD . Confirmation or refutation of this result may be achieved once the Towards a Revolution in COPD Health ( TORCH ) study reports , a large r and omized controlled trial powered to detect mortality changes associated with the use of FP alone , or in combination with salmeterol , which is also collecting re source use and utility data suitable for estimating cost-effectiveness OBJECTIVES To evaluate the clinical effectiveness , cost-effectiveness and safety of a policy of relatively early laparoscopic surgery compared with continued medical management amongst people with gastro-oesophageal reflux disease ( GORD ) judged suitable for both policies . DESIGN Relative clinical effectiveness was assessed by a r and omised trial ( with parallel non-r and omised preference groups ) comparing a laparoscopic surgery-based policy with a continued medical management policy . The economic evaluation compared the cost-effectiveness of the two management policies in order to identify the most efficient provision of future care and describe the re source impact that various policies for fundoplication would have on the NHS . SETTING A total of 21 hospitals throughout the UK with a local partnership between surgeon(s ) and gastroenterologist(s ) who shared the secondary care of patients with GORD . PARTICIPANTS The 810 participants , who were identified retrospectively or prospect ively via their participating clinicians , had both documented evidence of GORD ( endoscopy and /or manometry/24-hour pH monitoring ) and symptoms for longer than 12 months . In addition , the recruiting clinician(s ) was clinical ly uncertain about which management policy was best . INTERVENTION Of the 810 eligible patients who consented to participate , 357 were recruited to the r and omised arm of the trial ( 178 allocated to surgical management , 179 allocated to continued , but optimised , medical management ) and 453 recruited to the parallel non-r and omised preference arm ( 261 chose surgical management , 192 chose to continue with best medical management ) . The type of fundoplication was left to the discretion of the surgeon . MAIN OUTCOME MEASURES Participants completed a baseline REFLUX question naire , developed specifically for this study , containing a disease-specific outcome measure , the Short Form with 36 Items ( SF-36 ) , the EuroQol-5 Dimensions ( EQ-5D ) and the Beliefs about Medicines and Surgery question naires ( BMQ/BSQ ) . Postal question naires were completed at participant-specific time intervals after joining the trial ( equivalent to approximately 3 and 12 months after surgery ) . Intraoperative data were recorded by the surgeons and all other in-hospital data were collected by the research nurse . At the end of the study period , participants completed a discrete choice experiment question naire . RESULTS The r and omised groups were well balanced at entry . Participants had been taking GORD medication for a median of 32 months ; the mean age of participants was 46 years and 66 % were men . Of 178 r and omised to surgery , 111 ( 62 % ) actually had fundoplication . There was a mixture of clinical and personal reasons why some patients did not have surgery , sometimes related to long waiting times . A total or partial wrap procedure was performed depending on surgeon preference . Complications were uncommon and there were no deaths associated with surgery . By the equivalent of 12 months after surgery , 38 % in the r and omised surgical group ( 14 % amongst those who had surgery ) were taking reflux medication compared with 90 % in the r and omised medical group . There were substantial differences ( one-third to one-half st and ard deviation ) favouring the r and omised surgical group across the health status measures , the size depending on assumptions about the proportion that actually had fundoplication . These differences were the same or somewhat smaller than differences observed at 3 months . The lower the REFLUX score , the worse the symptoms at trial entry and the larger the benefit observed after surgery . The preference surgical group had the lowest REFLUX scores at baseline . These scores improved substantially after surgery , and by 12 months they were better than those in the preference medical group . The BMQ/BSQ and discrete choice experiment did distinguish the preference groups from each other and from the r and omised groups . The latter indicated that the risk of serious complications was the most important single attribute of a treatment option . A within-trial cost-effectiveness analysis suggested that the surgery policy was more costly ( mean 2049 pounds ) but also more effective [ + 0.088 quality -adjusted life-years ( QALYs ) ] . The estimated incremental cost per QALY was 19,000 - 23,000 pounds , with a probability between 46 % ( when 62 % received surgery ) and 19 % ( when all received surgery ) of cost-effectiveness at a threshold of 20,000 pounds per QALY . Modelling plausible longer-term scenarios ( such as lifetime benefit after surgery ) indicated a greater likelihood ( 74 % ) of cost-effectiveness at a threshold of 20,000 pounds , but applying a range of alternative scenarios indicated wide uncertainty . The expected value of perfect information was greatest for longer-term quality of life and proportions of surgical patients requiring medication . CONCLUSIONS Amongst patients requiring long-term medication to control symptoms of GORD , surgical management significantly increases general and reflux-specific health-related quality of life measures , at least up to 12 months after surgery . Complications of surgery were rare . A surgical policy is , however , more costly than continued medical management . At a threshold of 20,000 pounds per QALY it may well be cost-effective , especially when putative longer-term benefits are taken into account , but this is uncertain . The more troublesome the symptoms , the greater the potential benefit from surgery . Uncertainty about cost-effectiveness would be greatly reduced by more reliable information about relative longer-term costs and benefits of surgical and medical policies . This could be through extended follow-up of the REFLUX trial cohorts or of other cohorts of fundoplication patients . TRIAL REGISTRATION Current Controlled Trials IS RCT N15517081 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 This article presents the first version of a reporting format for modelling studies which is based on a general reporting format by our taskforce , which was published in the previous issue of this journal . The use of decision-analytical models for economic evaluations is increasing because , in practice , it is not always possible to derive information from prospect i ve studies . However , the acceptance of modelling studies is generally lower than prospect i ve studies not only because of the use of secondary data , but also because the reports of modelling studies do not always have sufficient transparency . Hence , a st and ardised reporting format may improve the transparency and , consequently , the acceptance of modelling studies . This article presents an example of a reporting format for economic evaluation based on modelling studies , which may facilitate the development of future guidelines for modelling studies . The format consists of a number of headings , which are followed by a brief recommendation on the content . This format does not deal with methodology and data management , but especially addresses validation and quality assurance , which may increase the transparency of the report BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness -- in a primary -care setting --of leukotriene receptor antagonists ( LTRAs ) as an alternative to inhaled corticosteroids ( ICS ) for initial asthma controller therapy . OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy . METHODS An economic evaluation was conducted alongside a 2-year , pragmatic , r and omized controlled trial set in 53 primary -care practice s in the UK . Patients aged 12 - 80 years with asthma and symptoms requiring regular anti-inflammatory therapy ( n = 326 ) were r and omly assigned to LTRAs ( n = 162 ) or ICS ( n = 164 ) . The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Question naire , per point improvement in the Asthma Control Question naire and per QALY gained from the UK NHS and societal perspectives . RESULTS Over 2 years , re source use was similar between the two treatment groups , but the cost to society per patient was significantly higher for the LTRA group , at pounds sterling 711 versus pounds sterling 433 for the ICS group ( adjusted difference pounds sterling 204 ; 95 % CI 74 , 308 ) [ year 2005 values ] . Cost differences were driven primarily by differences in prescription drug costs , particularly study drug costs . There was a nonsignificant ( imputed , adjusted ) difference between treatment groups , favouring ICS , in QALYs gained at 2 years of -0.073 ( 95 % CI -0.143 , 0.010 ) . Therapy with LTRAs was , on average , a dominated strategy , and , at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained , the probability of LTRAs being cost effective compared with ICS was approximately 3 % from both societal and NHS perspectives . CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK , at 2005 values , compared with ICS for initial asthma controller therapy . TRIAL REGISTRATION UK National Research Register N0547145240 ; Controlled Clinical Trials IS RCT N99132811 Background — In patients with severe aortic stenosis who can not have surgery , transcatheter aortic valve replacement ( TAVR ) has been shown to improve survival and quality of life compared with st and ard therapy , but the costs and cost-effectiveness of this strategy are not yet known . Methods and Results — The PARTNER trial r and omized patients with symptomatic , severe aortic stenosis who were not c and i date s for surgery to TAVR ( n=179 ) or st and ard therapy ( n=179 ) . Empirical data regarding survival , quality of life , medical re source use , and hospital costs were collected during the trial and used to project life expectancy , quality -adjusted life expectancy , and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective . For patients treated with TAVR , mean costs for the initial procedure and hospitalization were $ 42 806 and $ 78 542 , respectively . Follow-up costs through 12 months were lower with TAVR ( $ 29 289 versus $ 53 621 ) because of reduced hospitalization rates , but cumulative 1-year costs remained higher ( $ 106 076 versus $ 53 621 ) . We projected that over a patient 's lifetime , TAVR would increase discounted life expectancy by 1.6 years ( 1.3 quality -adjusted life-years ) at an incremental cost of $ 79 837 . The incremental cost-effectiveness ratio for TAVR was thus estimated at $ 50 200 per year of life gained or $ 61 889 per quality -adjusted life-year gained . These results were stable across a broad range of uncertainty and sensitivity analyses . Conclusions — For patients with severe aortic stenosis who are not c and i date s for surgery , TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00530894 |
11,183 | 27,801,522 | We did not note any major adverse events - the main consistent observation was burning or stinging sensation with the use of NSAIDs .
Using topical NSAIDs may reduce the risk of developing macular oedema after cataract surgery , although it is possible that current estimates as to the size of this reduction are exaggerated .
It is unclear the extent to which this reduction has an impact on the visual function and quality of life of patients .
There is little evidence to suggest any important effect on vision after surgery .
Future trials should address the remaining clinical uncertainty of whether prophylactic topical NSAIDs are of benefit , particularly with respect to longer-term follow-up ( at least to 12 months ) , and should be large enough to detect reduction in the risk of the outcome of most interest to patients , which is chronic macular oedema leading to visual loss | BACKGROUND Macular oedema ( MO ) is the accumulation of extracellular fluid in the central retina ( the macula ) .
It may occur after cataract surgery and may give rise to poor visual outcome , with reduced visual acuity and distortion of the central vision .
MO is often self-limiting with spontaneous resolution , but a small proportion of people with chronic persistent MO may be difficult to treat .
Chronic oedema may lead to the formation of cystic spaces in the retina termed ' cystoid macular oedema ' ( CMO ) .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) are commonly used in cataract surgery and may reduce the chances of developing MO .
OBJECTIVES The aim of this review is to answer the question : is there evidence to support the prophylactic use of topical NSAIDs either in addition to , or instead of , topical steroids postoperatively to reduce the incidence of macular oedema ( MO ) and associated visual morbidity . | Background The purpose of this study was to evaluate nepafenac ophthalmic suspension 0.1 % ( Nevanac ® ; Alcon Research Ltd ) in the prevention of macular edema following cataract surgery in diabetic retinopathy patients . Methods This was a multicenter , r and omized , double-masked , vehicle-controlled study of 263 adult diabetic patients with nonproliferative diabetic retinopathy requiring cataract surgery . Patients were r and omized ( 1:1 ) to instill nepafenac or vehicle three times daily beginning 1 day prior to surgery through day 90 . Efficacy included the percentage of patients who developed macular edema ( ≥30 % increase in central subfield macular thickness from baseline ) and the percentage of patients with decreases of more than five letters in best-corrected visual acuity from day 7 to 90 . Results A significantly lower percentage of patients in the nepafenac group developed macular edema relative to patients in the vehicle group ( 3.2 % versus 16.7 % ; P < 0.001 ) . A significantly lower percentage of patients in the nepafenac group had best-corrected visual acuity decreases of more than five letters relative to patients in the vehicle group on day 30 ( P < 0.001 ) , day 60 ( P = 0.002 ) , and day 90 ( P = 0.006 ) . The mean central subfield macular thickness and mean percent change from baseline in macular volume were also significantly lower in the nepafenac group versus the vehicle group at days 14 through 90 ( P ≤ 0.005 ) . No safety issues or trends were identified when dosing was increased to 90 days that negatively impacted the favorable benefit/risk profile of nepafenac . Conclusion Nepafenac demonstrated statistically significant and clinical ly relevant advantages compared with vehicle in preventing macular edema and maintaining visual acuity in diabetic patients following cataract surgery . These advantages were seen at multiple time points over the course of the 90-day therapy period . There was no clinical ly relevant increase in risk from 90 days dosing compared with 14 days . Therefore , with a similar safety profile and benefit in preventing macular edema and maintaining vision , the risk/benefit to the diabetic patient undergoing cataract surgery appears to be positive Purpose To evaluate the use of topical nepafenac 0.1 % after routine phacoemulsification in patients at low risk for cystoid macular oedema ( CME ) using optical coherence tomography ( OCT ) measurement of macular thickness . Methods Seventy-nine subjects with no risk factors for CME had uncomplicated bimanual micro-incision cataract surgery by an experienced surgeon . All subjects received preoperative nepafenac . Subjects were r and omised to postoperative st and ard of care , consisting of a topical antibiotic for 10 days and topical corticosteroid for 1 month ( control ) , or st and ard of care plus nepafenac for 1 month ( treatment ) . OCT and ETDRS best-corrected visual acuity were measured preoperatively and 2 months postoperatively . Primary endpoints were comparison of changes in macular thickness between groups and the relationship of that change to postoperative vision . Results All subjects had excellent visual outcomes , with mean visual improvement of 15 letters . Cataract surgery was very efficient with a mean effective phaco time ( EPT ) of 4.99 and 6.90 s in the control and treatment groups , respectively . There were small increases in the central macular thickness in both the control ( 2.78 μm ) and treatment ( 5.60 μm ) groups . The change in macular thickness was statistically similar between groups and did not correlate with the final visual outcome . Discussion The small increase in macular thickness after routine cataract surgery is probably not clinical ly significant . In subjects undergoing routine cataract surgery , and at low risk for CME , the routine use of preoperative nepafenac may be all that is necessary to achieve excellent visual recovery PURPOSE To access the necessity of topical steroids after uneventful cataract surgery , phaco-emulsification/aspiration plus intraocular lens ( PEA+IOL ) implantation . DESIGN Single-blind , r and omized , prospect i ve study . PARTICIPANTS Twenty-one patients were prospect ively r and omized , 11 patients were assigned to the steroid group , and 10 to the non-steroid group . METHODS Between March and September 2007 , in Mino Tanaka Hospital in Tokushima Prefecture , Japan , we performed PEA+IOL in 28 eyes of 21 patients and examined the visual acuity , corneal endothelium cell density , and anterior aqueous flare value after dividing all the patients into 2 groups , the topical steroid use and the non-steroid group . RESULTS At 1 month postoperatively , no difference was observed between the 2 groups in terms of the outcomes described , and no cystoid macular edema was detected . CONCLUSION Topical steroid medication may not be absolutely essential after uneventful PEA+IOL Purpose To compare the anti-inflammatory efficacy of ketorolac of tromethamine 0.4 % and nepafenac 0.1 % eye drops for prophylaxis of cystoid macular oedema ( CME ) after small-incision cataract extraction . Methods Patients were assigned r and omly to three groups . Group 1 patients received a topical artificial tear substitute ( placebo ) ; group 2 received ketorolac tromethamine 0.4 % ( Acular LS , Allergan ) and group 3 received nepafenac 0.1 % ( Nevanac , Alcon ) . The incidence and severity of CME were evaluated by retinal foveal thickness on optical coherence tomography ( OCT ) after 1 , 4 and 12 weeks . Results One hundred and twenty-six eyes of 126 patients were included in this study . The between-group differences in visual outcomes , central corneal thickness and endothelial cell density were not statistically significant . In all retinal thickness measurements , an increase was detected starting from the postoperative first week until 12 weeks . There was no statistically significant difference between the three groups in any measurement performed by spectral-domain OCT . Conclusions Used prophylactically after uneventful cataract surgery , non-steroidal anti-inflammatory drugs were not efficacious in preventing macular oedema compared with placebo . Trial registration number Clinical Trials : NCT02084576 PURPOSE : To evaluate the effectiveness of a nonsteroidal antiinflammatory drug ( NSAID ) on pseudophakic cystoid macular edema ( CME ) and determine the efficacy when used preoperatively and after uneventful phacoemulsification surgery . SETTING : Department of Ophthalmology , Kocatepe University , School of Medicine , Afyonkarahisar , Turkey . METHODS : One hundred seventy‐nine eyes of 189 patients having uneventful phacoemulsification surgery were enrolled in the study . After surgery , all patients used topical steroids and antibiotics 4 times daily . Sixty‐one eyes , chosen r and omly , received a topical NSAID ( indomethacin ) 4 times daily for 3 days preoperatively and 1 month postoperatively . Sixty eyes received topical indomethacin 4 times daily for 1 month postoperatively . Fifty‐eight eyes served as a control group and received only topical steroids and antibiotics . At the third postoperative month , visual acuity , fluorescein angiograms , and macular thresholds were evaluated . Statistical analysis was by chi‐square and 1‐way analysis of variance tests . RESULTS : Cystoid macular edema was not seen in the group receiving indomethacin preoperatively and postoperatively . The incidence of angiographic CME was 15.0 % in the group receiving postoperative indomethacin and 32.8 % in the control group ( P<.001 ) . Mean sensitivity in the macular threshold test did not show a significant change between groups ( P = .83 ) . Postoperative visual acuity was significantly higher in the group receiving preoperative indomethacin ( P<.001 ) . CONCLUSION : Nonsteroidal antiinflammatory drugs decreased the incidence of CME , and their efficacy increased when begun preoperatively PURPOSE To evaluate whether adding perioperative topical ketorolac tromethamine 0.4 % improves cataract surgery outcomes relative to topical steroids alone in patients without known risk factors for cystoid macular edema ( CME ) . DESIGN Prospect i ve , r and omized , investigator-masked , multicenter clinical trial . METHODS Patients scheduled to undergo phacoemulsification and with no recognized CME risks ( diabetic retinopathy , retinal vascular disease , or macular abnormality ) were r and omized to receive either prednisolone acetate 1 % 4 times daily ( QID ) alone ( steroid group ; n = 278 ) or prednisolone 1 % QID plus ketorolac 0.4 % QID ( ketorolac/steroid group ; n = 268 ) for approximately four weeks postoperatively . In the ketorolac/steroid group , patients also received topical ketorolac 0.4 % QID for three days preoperatively . In both groups , patients received four doses of ketorolac 0.4 % one hour before surgery . Patients with capsular disruption or vitreous loss intraoperatively were exited from the study . Outcome measures included CME incidence , retinal thickness as measured by optical coherence tomography ( OCT ) , best-corrected visual acuity , and contrast sensitivity . RESULTS No patients in the ketorolac/steroid group and five patients in the steroid group had clinical ly apparent CME ( P = .032 ) . Based on OCT , no ketorolac/steroid patient had definite or probable CME , compared with six steroid patients ( 2.4 % ; P = .018 ) . In the ketorolac/steroid group , mean retinal thickening was less ( 3.9 microm vs 9.6 microm ; P = .003 ) , and fewer patients had retinal thickening of more than 10 microm as compared with the steroid group ( 26 % vs 51 % ; P < .001 ) . CONCLUSIONS This study suggests that adding perioperative ketorolac to postoperative prednisolone significantly reduces the incidences of CME and macular thickening in cataract surgery patients already at low risk for this condition Purpose To evaluate the efficacy of adding nepafenac 0.1 % ophthalmic suspension to dexamethasone 0.1 % eyedrops in controlling macular swelling and other manifestations of inflammation after uneventful cataract surgery . Setting Ophthalmology Department , Mölndal Hospital , Gothenburg , and St. Erik Eye Hospital , Stockholm , Sweden . Design R and omized double‐masked clinical trial . Methods Patients at low risk for postoperative inflammation were recruited and r and omized to the nepafenac group or to the control group . Postoperative swelling of the macula was assessed with ocular coherence tomography . Laser flare intensity , corrected distance visual acuity , ocular discomfort , and visual complaints were also recorded . Results The analysis of intent‐to‐treat population comprised 75 patients in the nepafenac group and 77 patients in the control group . Compared with the control regimen , add‐on nepafenac result ed in statistically significant reductions in the following parameters : change in macular volume at 3 weeks and 6 weeks ( P<.001 ) , proportion of patients with more than 10 & mgr;m of swelling in the central macula at 3 weeks ( P<.0001 ) and 6 weeks ( P=.02 ) , mean laser flare intensity at 1 day ( P=.029 ) , pain during the first 24 hours postoperatively ( P<.0001 ) , and ocular discomfort and photophobia during the first 3 postoperative weeks ( P=.0058 and P=.0052 , respectively ) . Conclusion The combination of topical nepafenac and steroid treatment reduced sub clinical macular swelling and inflammation as well as subjective complaints , indicating it is an efficient antiinflammatory regimen after cataract surgery . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned Purpose : To compare bromfenac sodium 0.1 % , fluorometholone 0.1 % and dexamethasone 0.1 % for the control of postoperative inflammation and prevention of cystoid macular edema ( CME ) after phacoemulsification . Methods : Patients were r and omized to receive bromfenac sodium 0.1 % for 1 month ( OBS1 ) or 2 months ( OBS2 ) , or fluorometholone 0.1 % for 1 month ( OFM ) or dexamethasone 0.1 % for 1 month ( ODM ) . Best-corrected visual acuity , intraocular pressure , endothelial cell density , photon count value and retinal foveal thickness were measured . Results : Mean photon count values were lower in the OBS1 and OBS2 groups compared with the ODM group during the first week . Bromfenac sodium cleared the ocular inflammation more rapidly than fluorometholone and dexamethasone . The foveal thickness was thinner in the second month and the incidence of CME was lower in the OBS1 and OBS2 groups compared with the OFM and ODM groups . Conclusion : Bromfenac sodium was more effective and safer than fluorometholone and dexamethasone as an anti-inflammatory , decreasing macular thickness and preventing CME in age-related cataract patients after cataract surgery Purpose To compare the additive effects of two types of non-steroidal anti-inflammatory drugs ( NSAIDs ) , bromfenac 0.1 % or ketorolac 0.45 % , relative to topical steroid alone in cataract surgery . Material s and Methods A total 91 subjects scheduled to undergo cataract operation were r and omized into three groups : Group 1 , pre/postoperative bromfenac 0.1 % ; Group 2 , pre/postoperative preservative-free ketorolac 0.45 % ; and Group 3 , postoperative steroid only , as a control . Outcome measures included intraoperative change in pupil size , postoperative anterior chamber inflammation control , change in macular thickness and volume , and ocular surface status after operation . Results Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group ( p<0.05 ) . There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group . The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30±4.25 , 4.87±6.03 , and 12.47±12.24 µm in groups 1 to 3 , respectively . In the control group , macular thickness and volume increased more in patients with diabetes mellitus ( DM ) , compared to those without DM . In contrast , in both NSAID groups , NSAIDs significantly reduced macular changes in subgroups of patients with or without DM . Although three ocular surface parameters were worse in group 1 than in group 2 , these differences were not significant . Conclusion Adding preoperative and postoperative bromfenac 0.1 % or ketorolac 0.45 % to topical steroid can reduce intraoperative miosis , postoperative inflammation , and macular changes more effectively than postoperative steroid alone Two hundred and eighty-three patients scheduled to undergo extracapsular cataract extraction with intraocular lens implantation were r and omized into four treatment groups that received 1 % topical indomethacin and 0.1 % topical dexamethasone sodium phosphate , either drug and the other drug 's placebo , or two placebos . Inflammation was assessed by clinical grading , and the breakdown of the blood-aqueous barrier was evaluated by slit-lamp anterior segment fluorophotometry . Patients who used either or both anti-inflammatory agents had significantly less inflammation or blood-aqueous barrier breakdown than did those who used neither agent . Also , the use of both topical indomethacin and dexamethasone result ed in less fluorescein leakage during the second postoperative week than did the use of dexamethasone alone . Since this difference could not be detected by clinical measurement , we believe that fluorophotometry is a more sensitive quantitative measure . Clinical assessment of inflammation did correlate with fluorophotometric measurements , as patients with clinical ly unacceptable inflammation had 3.7 times more fluorescein leakage in the surgically treated eye than did patients with clinical ly acceptable inflammation PURPOSE To compare a nonsteroidal topical solution ( 0.1 % diclofenac ) to a steroidal topical solution ( 0.1 % fluorometholone ) in preventing cystoid macular edema ( CME ) and disruption of the blood-aqueous barrier . METHODS A multicentered , prospect i ve clinical trial was performed on eyes undergoing phacoemulsification followed by implantation of a foldable acrylic intraocular lens by the envelope technique . The presence and degree of cystoid macula edema ( CME ) was determined by fluorescein angiography . A breakdown of the blood-aqueous barrier was determined by laser flare-cell photometry . RESULTS Five weeks after surgery , CME was present in 3 of 53 eyes ( 5.7 % ) receiving diclofenac and in 29 of 53 eyes ( 54.7 % ) receiving fluorometholone . This difference was statistically significant ( P < .001 ) . The amount of flare in the anterior chamber at 3 days , 1 , 2 , 5 , and 8 weeks after surgery was also significantly lower ( P < .01-P < .001 ) in the diclofenac group . The degree of flare at 3 days , 1 , 2 , 5 , and 8 weeks after surgery was significantly higher in eyes with CME ( P < .001 ) . CONCLUSIONS These findings suggest that diclofenac effectively prevents CME following cataract surgery and that CME is closely related to the breakdown of the blood-aqueous barrier Purpose : The purpose of this study was to evaluate the addition of topical nonsteroidal antiinflammatory drugs ( NSAIDs ) to intravitreal corticosteroid and antivascular endothelial growth factor injections for the treatment of chronic cystoid macular edema . Methods : Thirty-nine patients with chronic pseudophakic cystoid macular edema completed a single-center , r and omized , investigator-masked study . All patients were treated with an intravitreal triamcinolone and bevacizumab injection at study entry ; the bevacizumab injection was repeated at 1 month . To evaluate the effect of adding an NSAID , patients were r and omized to treatment with 1 of 4 topical NSAIDs ( diclofenac 0.1 % , ketorolac 0.4 % , nepafenac 0.1 % , and bromfenac 0.09 % ) or placebo for 16 weeks . Results : At Weeks 12 and 16 , both the nepafenac and bromfenac groups showed a significant reduction in retinal thickness compared with that in placebo ( nepafenac , P = 0.0048 , bromfenac , P = 0.0113 ) . A difference , however , between these 2 NSAID groups was observed in that only the nepafenac group was able to maintain the demonstrated retinal thickness decrease at Weeks 12 and 16 . The nepafenac group also experienced a significant improvement in visual acuity at Weeks 12 ( P = 0.0084 ) and 16 ( P = 0.0233 ) . The addition of NSAIDs did not produce an increase in mean intraocular pressure over the course of therapy . Conclusion : Although NSAID therapy seems to potentiate the improvements produced by corticosteroids and antivascular endothelial growth factor therapy for chronic pseudophakic cystoid macular edema , only nepafenac- and bromfenac-treated eyes showed reduced retinal thickness at 12 weeks and 16 weeks . Furthermore , nepafenac produced a sustained improvement in visual acuity PURPOSE To determine the efficacy of topical ketorolac tromethamine in preventing cystoid macular edema ( CME ) after uncomplicated cataract surgery . METHODS This single-center , prospect i ve , double-masked , r and omized clinical trial consisted of 81 patients who were scheduled for cataract surgery . Patients were r and omized to receive hypromellose/dextran 70 as a placebo ( n=44 ) or ketorolac tromethamine 0.4 % ( n=37 ) as an adjuvant therapy . These eye drops were administered 4 times daily ( QID ) for 3 days before surgery and 5 weeks postoperatively . All patients received prednisolone acetate 1 % QID during the same period as basal/st and ard anti-inflammatory therapy . The primary outcome was the incidence of angiographic CME 5 weeks after surgery . The secondary outcomes were mean change in best-corrected visual acuity ( BCVA ) [ Early Treatment Diabetic Retinopathy study ( ETDRS ) ] , clinical CME incidence , intraocular pressure , and retinal thickness measured using optical coherence tomography ( OCT ) . RESULTS In the placebo group , 2/44 ( 4.5 % ) patients and in the ketorolac group , 2/37 ( 5.4 % ) patients presented with angiographic CME ( P=0.624 ) . The mean change in postoperative BCVA was 32±15 letters in the placebo group and 26±16 letters in the ketorolac group ( P=0.07 ) . There were no statistically significant between-group differences in the mean central subfield thickness ( P=0.679 ) , minimal central thickness ( P=0.352 ) , or central macular volume ( P=0.729 ) . CONCLUSION There was no difference between ketorolac tromethamine and a placebo with regard to BCVA results or prevention of CME after uncomplicated cataract surgery Objective : To evaluate the effectiveness of prophylactic administration of nepafenac 0.1 % in maintaining mydriasis and in preventing postoperative macular edema following cataract surgery . Methods : This was a prospect i ve , r and omized , single-masked comparative study in 60 patients undergoing phacoemulsification cataract surgery . Patients were r and omized to either the nepafenac or the control group . Nepafenac was administered 3 times daily 1 day before surgery and continued for 6 weeks . The control group received tobramycin-dexamethasone treatment only . Trans-operative mydriasis was measured before surgery , after nuclear emulsification , following cortex aspiration , and at the conclusion of surgery . Macular optical coherence tomography determined central foveal thickness ( FT ) and total macular volume ( TMV ) before surgery and at 2 and 6 weeks after surgery . All patients received tobramycin-dexamethasone for 2 weeks after surgery . Results : The difference in mean pupil size , at the end of surgery , between the control group ( 6.84 ± 0.93 mm ) and the nepafenac group ( 7.91 ± 0.74 mm ) was statistically significant ( p < 0.001 ) . There were no significant differences in FT values between the two groups at any time point ; however , TMV at 2 and at 6 weeks was statistically significantly different ( p < 0.001 ) , with higher TMV in the control group . Conclusion : Prophylactic use of nepafenac was effective in reducing macular edema after cataract surgery and in maintaining trans-operative mydriasis PURPOSE To investigate the efficacy and safety of ketorolac tromethamine 0.5 % ophthalmic solution ( Acular ; Allergan , Inc , Irvine , California ) in the treatment of moderate to severe anterior segment inflammation developing after unilateral cataract surgery with intraocular lens implantation . METHODS Only patients who exhibited moderate or greater levels of cells and flare 1 day after surgery were included in this multicenter , double-masked , r and omly assigned , parallel-group study . Topical ketorolac or vehicle solution ( Allergan , Inc ) was administered to the treated eye four times daily , starting the day after surgery and continuing for 14 days . RESULTS Ketorolac was significantly more effective than the vehicle solution in reducing anterior chamber cells ( P < or = .030 ) and flare ( P < or = .025 ) , conjunctival erythema ( P < or = .046 ) , ciliary flush ( P < or = .006 ) , tearing ( P < or = .012 ) , photophobia ( P < or = .014 ) , and pain ( P < or = .049 ) . Half as many patients from the ketorolac group ( 14/51 ) were discontinued from the study for lack of efficacy , compared with the vehicle group ( 28/51 ; P = .005 ) . There was no significant difference between ketorolac and the vehicle solution in changes in visual acuity , intraocular pressure , biomicroscopic or ophthalmoscopic variables , or adverse events . CONCLUSIONS Ketorolac tromethamine 0.5 % ophthalmic solution is safe and provides substantial anti-inflammatory activity in the treatment of moderate to severe anterior segment inflammation developing after cataract surgery and intraocular lens implantation Anterior chamber fluorophotometry was done after the oral administration of fluorescein sodium in patients undergoing extracapsular cataract extraction and posterior chamber intraocular lens insertion before and after surgery . The administration of ketorolac solution 0.5 % eye drops before and after surgery decreased the breakdown of the blood-aqueous barrier as much as did dexamethasone sodium phosphate solution 0.1 % ( dexamethasone solution ) eye drops at each postoperative time period as measured by fluorophotometry . Slit-lamp observations of postoperative anterior ocular inflammation were not different between treatment groups . Both ketorolac and dexamethasone solutions were well tolerated by patients . No additional corticosteroids were given to any patients during the study . Therefore , ketorolac solution was as effective as dexamethasone solution in suppressing postoperative inflammation after cataract surgery as measured by fluorophotometry and as observed by slit-lamp examinations . This study confirms prior studies that suggest ketorolac ophthalmic solution 0.5 % may be effective and safe as a nonsteroidal antiinflammatory agent for topical use after cataract surgery and intraocular lens implantation and as a substitute for topically applied corticosteroids The effect of ketorolac tromethamine 0.5 % ophthalmic solution ( a new nonsteroidal anti-inflammatory agent ) treatment was compared to placebo treatment in patients with chronic , angiographically proven aphakic or pseudophakic cystoid macular edema ( visual acuity less than or equal to 20/40 for six months ) during a three- to four-month double-masked , r and omized study . Twenty-six patients completed this study without significant ocular or systemic toxicity . The improved distance visual acuity observed in the ketorolac treatment group ( 8/13 patients ) was statistically different from the improved vision observed in the placebo treated group ( 1/13 patients ) ( P = .005 ) . No patient on a regimen of ketorolac therapy had a significant decrease in Snellen distance visual acuity while on treatment , but two patients in the placebo group demonstrated a decrease in visual acuity of two lines or more . Fluorescein angiography was consistent with changes in visual acuity In a r and omized , controlled study drops of 1 % aqueous solution of indomethacin were compared to Placebo to assess efficacy in the prevention of cystoid macular edema . The study involved 124 patients who had undergone intracapsular cataract extraction and 40 patients with implanted lenses . The study parameters -- visual acuity , biomicroscopy observations of the macula and fluorescein angiography -- were assessed for three months postoperatively . The long-term course was review ed by regular outpatient follow-up visits or by question naires completed by the patients ' personal ophthalmologists . Fluorescein angiography could only be carried out in 13 of the 40 patients who had intraocular lenses . The relatively high incidence of secondary cataract or pupillary synechiae made technically perfect exposures difficult . In 73 patients with intracapsular extraction , fluorescein angiography showed a distinct diminution in the incidence of edema in the indomethacin group at all three observation periods ( 3 , 6 and 12 weeks postoperatively ) . The difference compared with placebo was significant at weeks 6 and 12 . Ophthalmoscopically visible macular changes were rare . No evidence of edema was noted in any of the 51 patients who could not have fluorescein angiography for one reason or another . The visual acuity of patients who received indomethacin was not significantly different from that of those who received placebo . Furthermore , and this is important for the patients , in the group with proven edema no conclusion could be made about the effect of therapy on the severity and persistence of visual impairment . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE The purpose of our study was to evaluate the effectiveness of preoperative and postoperative addition of topical diclofenac to chloramphenicol/dexamethasone in patients undergoing uneventful phacoemulsification cataract surgery . METHODS Patients were r and omized to ( 1 ) chloramphenicol 0.5%-dexamethasone 0.1 % , 1 drop 4 times a day ( n=41 ) , or ( 2 ) chloramphenicol 0.5%-dexamethasone 0.1 % , 1 drop 4 times a day , plus diclofenac 0.1 % , 1 drop 3 times a day ( n=38 ) . Patients in the second group also received diclofenac 0.1 % for 3 days before surgery . Topical treatment was administered for 28 days after phacoemulsification . On postoperative days 1 , 14 , and 28 , best corrected visual acuity , macular thickness , endothelial cell density , and central corneal thickness ( CCT ) were measured . RESULTS The 2 groups did not have a statistically significant difference for CCT , endothelial cell density , macular thickness , and visual acuity at the 3 time points of the follow-up period . CONCLUSIONS The addition of diclofenac did not seem to offer any additional benefit after uneventful phacoemulsification A prospect i ve double-masked study of 500 patients was performed to assess the effect of topical indomethacin on the angiographic incidence of cystoid macular edema ( CME ) in patients undergoing intraocular lens implant surgery . All patients received either topical indomethacin or placebo before surgery and for nine months after surgery . All patients underwent planned extracapsular extraction ( PEC ) or posterior chamber phacoemulsification ( PC-KPE ) . Implantation of a posterior chamber lens and a primary capsulotomy were performed in all cases . All cases received postoperative topical corticosteroids . Of the 500 cases , 390 ( 78 % ) underwent fluorescein angiography ; most were performed between 2 1/2 and 5 months after surgery . The incidence of angiographically confirmed CME was significantly higher in the placebo-treated patients as compared to those treated with indomethacin ( 18.5 % vs 9.6 % ; P = 0.04 ) . Patients 60 years of age or older had a significantly higher incidence of CME than younger individuals ( 15 % vs. 3.4 % ; P = 0.03 ) . When corrected for the effects of drug regimen and age , by means of multiple logistic regression , there was no significant correlation between procedure ( PEC vs. PC-KPE ) and CME rate ( P = 0.62 ) . There was no significant difference in postoperative visual acuity between the indomethacin- and placebo-treated patients ( P = 0.65 ) Purpose : To compare the efficacy and tolerance of diclofenac 0.1 % eyedrops with a regimen that included a brief course of steroids in the treatment of postoperative inflammation after extracapsular cataract surgery and posterior chamber intraocular lens implantation . A second objective was to compare the efficacy of diclofenac 0.1 % eyedrops in the same patients and control group in preventing cystoid macular edema ( CME ) . Setting : Eight university/hospital centers and one company in Italy . Methods : The multicenter , controlled , r and omized , prospect i ve , double‐blind study included 281 patients . All were evaluated at baseline , at surgery , and after 1 , 5 , 36 , 67 , and 140 days . Postoperative inflammation was measured by the clinical assessment of inflammation : conjunctival hyperemia , ciliary flush , Tyndall effect , and cells in the anterior chamber . Fluorescein angiography was performed to evaluate the presence/absence of CME before surgery and after 36 and 140 days . Results : During follow‐up , no differences in intraoperative pressure were observed within or between groups or between operated and fellow eyes . No statistically significant between‐group differences in postoperative inflammation were found . After 36 days , angiographic CME was found in 9 patients ( 6.43 % ) in the diclofenac group and 20 ( 15.15 % ) in the control group ( P = .033 ) with a relative risk for developing CME of 0.40 ( Cl95 0.19 to 0.84 ) . At the end of follow‐up , it was found in 4 patients in the diclofenac group ( 3.31 % ) and 10 ( 9.26 % ) in the control group ( P = .05 ) with a relative risk of 0.36 ( Cl95 0.12 to 0.90 ) . Conclusion : Diclofenac sodium was as effective as the control regimen in controlling postoperative inflammation after cataract surgery . It also had a protective effect on the development of angiographic CME after 36 and 140 days PURPOSE : To evaluate the efficacy of prophylactic administration of the topical nonsteroidal antiinflammatory drug ( NSAID ) ketorolac tromethamine 0.5 % on acute ( within 4 weeks of surgery ) cystoid macular edema ( CME ) and total macular volume ( TMV ) in patients having phacoemulsification cataract surgery . SETTING : Department of Ophthalmology , Queen 's University , Hotel Dieu Hospital , Kingston , Ontario , Canada . METHODS : This open‐label nonmasked r and omized ( r and om number assignment ) study comprised 106 eyes of 98 patients . Exclusion criteria included hypersensitivity to the NSAID drug class , aspirin/NSAID‐induced asthma , and pregnancy in the third trimester . Ketorolac tromethamine 0.5 % was administered starting 2 days before surgery and for 29 days after surgery for a total of 31 days . The outcome measure was macular swelling , which was quantified by the optical coherence tomography . RESULTS : At 1 month , there was a statistically significant difference in TMV between the control group ( 0.4420 mm3 ) and the ketorolac group ( 0.2392 mm3 ) , with the ketorolac group having 45.8 % less macular swelling ( P = .009 ) . Multiple linear regression with backward selection indicated a 44.3 % ( P = .013 ) and 46.1 % ( P = .030 ) reduction in macular swelling in the ketorolac group at 1 week and 1 month , respectively . CONCLUSION : Used prophylactically after cataract surgery , ketorolac 0.5 % was efficacious in decreasing postoperative macular edema Diclofenac is superior to other nonsteroid anti-inflammatory drugs ( NAD ) with respect to its antiphlogistic properties , as demonstrated in laboratory animal experiments . The antiphlogistic action of diclofenac eyedrops versus placebo eyedrops in the prophylaxis of cystoid macular edema ( CME ) and postoperative inflammatory symptoms was therefore tested in a prospect i ve r and omized double-blind study . A total of 179 patients with intracapsular cataract operations and Choyce Mark IX anterior chamber lens implantation received 2 drops 5 times preoperatively and 1 drop 5 times postoperatively until they were discharged , and then subsequently for 6 months they used 1 drop of diclofenac or placebo eyedrops 3 times . To evaluate the CME , fluorescence angiography was carried out on all patients on the day of discharge , 6 weeks later , and after 6 months following the operation . The patients who completed the study according to plan numbered 112 . With diclofenac eyedrops , significantly less CME occurred in comparison with treatment with placebo eyedrops ( p = 0.03 ) . Visual acuity improved faster and the postoperative inflammatory symptoms receded more quickly in the diclofenac group A prospect i ve , controlled study utilizing topical 1 % aqueous indomethacin was employed in an attempt to determine the incidence of aphakic cystoid macular edema ( ACME ) following cataract surgery . The incidence of ACME in the indomethacin-treated group was significantly less than in the control group five weeks after cataract surgery ( 36 % vs 18 % ; P less than 0.02 ) . There was no significant difference in the two groups ten weeks after surgery when studied by fluorescein angiography ( 34.6 % vs 21 % ; P less than 0.10 ) . The biochemical and pharmacological rationale for the use of the antiprostagl and in indomethacin in the management of ACME was review ed . This revealed sufficient experimental and clinical evidence for continued research in the area of prostagl and in inhibitors for the possible prevention or treatment of this disorder PURPOSE To ascertain the incidence of cystoid macular edema ( CME ) after phacoemulsification and its relationship to blood-aqueous barrier damage and visual acuity . SETTING A British teaching hospital . METHODS A prospect i ve trial was performed to document the incidence of CME after routine phacoemulsification with continuous curvilinear capsulorhexis . LogMAR visual acuity and laser flare were measured using the KOWA FC 1000 laser cell-flare meter preoperatively and 1 , 14 , 30 , and 60 days postoperatively . At day 60 , a st and ardized fluorescein angiogram was performed and grade d by masked observers . RESULTS The rate of angiographic CME on day 60 was 19 % . Visual acuity at each visit was significantly worse in the CME group ( P < .05 ) . The flare and cell values at days 14 , 30 , and 60 were higher in the CME group at day 60 ; however , the difference was not statistically significance ( P > .05 ) . CONCLUSIONS The incidence of CME after routine phacoemulsification was 19 % . Patients with CME at day 60 had significantly worse visual acuity than those who did not from the first postoperative day throughout the follow-up . There was a trend for patients who had CME at day 60 to have more postoperative inflammation PURPOSE : To assess the clinical benefit , relative efficacy , and pharmacokinetic‐response curve of preoperative and postoperative ketorolac tromethamine 0.4 % ( Acular LS ) to improve outcomes during and after cataract surgery . SETTING : Private clinical practice . METHODS : One hundred patients were r and omized in a double‐masked fashion to 4 groups of 25 to receive ketorolac for 3 days , 1 day , or 1 hour or a placebo before phacoemulsification . All treatment groups received ketorolac 0.4 % for 3 weeks postoperatively ; the placebo group received vehicle . Outcomes measures were preservation of preoperative mydriasis , phacoemulsification time and energy , operative time , corneal clarity , endothelial cell counts , postoperative inflammation , intraoperative and postoperative discomfort , complications , and incidence of clinical ly significant cystoid macular edema ( CME ) . RESULTS : Maintenance of pupil size with 3‐day ketorolac dosing was significantly better than with 1‐day dosing ( P<.01 ) , which was significantly better than with 1‐hour or placebo dosing ( P<.01 ) . Both 3‐day and 1‐day dosing were superior to 1‐hour or placebo dosing . No patient receiving ketorolac 0.4 % for 1 or 3 days developed CME compared with 12 % of patients in the control ( placebo ) group and 4 % in the 1‐hour group . Three‐day and 1‐day dosing of ketorolac reduced surgical time , phacoemulsification time and energy , and endothelial cell loss and improved visual acuity in the immediate postoperative period compared with 1‐hour predosing and the placebo ( P<.05 ) . CONCLUSION : The preoperative use of ketorolac tromethamine 0.4 % for 3 days followed by 1‐day of predosing provided optimum efficacy and superior outcomes relative to 1‐hour pretreatment and a placebo PURPOSE To study the chronological change in choroidal blood flow ( ChBFlow ) , disruption of the blood-aqueous barrier , and incidence of cystoid macular edema ( CME ) in early postoperative pseudophakic eyes , as well as the effect of nonsteroidal anti-inflammatory drug ( NSAID ) eye drops on these phenomena . METHODS Fifty patients who underwent phacoemulsification and foldable intraocular lens ( IOL ) implantation were r and omized to receive either topical diclofenac or fluorometholone for 5 postoperative weeks . An additional 20 subjects , with long-st and ing pseudophakia served as the control . The blood-aqueous barrier was examined by laser flarimetry and choroidal blood velocity ( ChBVel ) , volume ( ChBVol ) , and ChBFlow by laser Doppler flowmetry ( LDF ) at 2 days and 1 , 2 , and 5 weeks after surgery . The incidence and severity of CME were evaluated by fluorescein angiography at 2 and 5 weeks after surgery . RESULTS Compared with patients taking diclofenac , those receiving fluorometholone showed significantly reduced ChBVol at 2 weeks ( 0.38 + /- 0.08 vs. 0.32 + /- 0.07 , P = 0.022 ) and ChBFlow at 1 ( 11.01 + /- 1.74 vs. 9.35 + /- 1.51 , P = 0.003 ) and 2 ( 11.15 + /- 1.43 vs. 8.47 + /- 1.27 , P = 0.000 ) weeks after surgery , as well as a significantly elevated amount of anterior flare at 1 ( 8.9 + /- 2.2 vs. 24.4 + /- 18.9 , P = 0.001 ) and 2 ( 9.2 + /- 3.5 vs. 16.7 + /- 12.3 , P = 0.025 ) weeks after surgery . The ChBVol and ChBFlow in the fluorometholone group , however , returned to normal and was not different from the diclofenac group at 5 weeks after surgery . The incidence of fluorescein angiographic CME trended to be higher ( P = 0.08 ) at 2 weeks and was significantly higher ( P = 0.001 ) at 5 weeks after surgery in eyes with fluoromethalone than with diclofenac . CONCLUSIONS Reduction of ChBFlow , disruption of the blood-aqueous barrier , and incidence of CME in early postsurgical pseudophakic eyes were more effectively prevented chronologically in eyes treated with diclofenac than in those treated with fluorometholone It has been theorized that prostagl and ins E1 and E2 may be responsible for the vascular leakage leading to cystoid macular edema following cataract extraction . Indomethacin is a known inhibitor of prostagl and in synthesis . A prospect i ve , double-blind study to evaluate the effect of oral indomethacin on four and eight week cases of postoperative CME following intracapsular cataract extraction as determined by fluorescein angiography was carried out on 42 patients . Twenty patients received 25 mg of indomethacin three times a day for three days preoperatively and three weeks postoperatively . Twenty-two patients received a placebo on an identical schedule . Four ( 20 % ) patients in the indomethacin group and five ( 22.7 % ) patients in the placebo group had positive angiograms for CME . No contributory factor result ing in CME was found OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) Purpose To evaluate the efficacy of prophylactic ketorolac 0.5 % versus nepafenac 0.1 % versus placebo on macular volume 1 month after uneventful phacoemulsification and evaluate the health‐related quality ‐of‐life ( HRQOL ) of topical nonsteroidal antiinflammatory drugs ( NSAIDs ) in the context of cataract surgery . Setting Hotel Dieu Hospital , Kingston , Ontario , Canada . Design Prospect i ve placebo‐controlled parallel‐assignment double‐masked r and omized clinical trial . Methods In this study , patients 18 years or older scheduled for routine phacoemulsification were r and omized to a placebo , ketorolac 0.5 % , or nepafenac 0.1 % and dosed 4 times a day starting 1 day before surgery and continuing for 4 weeks . Spectral‐domain macular cube ocular coherence tomography scans measuring central subfield thickness , macular cube volume , and average macular cube thickness were performed at baseline and 1 month postoperatively . The HRQOL metrics were determined with the Comparison of Ophthalmic Medications for Tolerability ( COMTOL ) question naire . Results Each study group comprised 54 patients . One month postoperatively , although a trend toward significance occurred for nepafenac and ketorolac , analysis of the means of differences showed no statistically significant differences between the 3 study groups ( P=.2901 ) . The COMTOL analysis found no difference in tolerability , compliance , side‐effect frequency and bother , and effects on HRQOL between ketorolac and nepafenac compared with the placebo . Conclusions One month after uneventful phacoemulsification , there was no difference in macular volume between the placebo , ketorolac , and nepafenac . Ketorolac and nepafenac were well tolerated with minimal side‐effect profiles . Thus , for patients without risk factors having routine surgery , prophylactic topical NSAIDs are not recommended . Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned PURPOSE To compare the efficacy and safety of ketorolac 0.5 % ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation . DESIGN Multicenter clinical study . PARTICIPANTS One hundred four patients were prospect ively r and omized , 52 patients in treatment group , 52 patients in control group . METHODS Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospect i ve , double-masked , r and omized , parallel group study . Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled . MAIN OUTCOME MEASURES The main outcome measures include inflammation ( cell , flare , ciliary flush ) , intraocular pressure and visual acuity . RESULTS Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation , including : anterior chamber cells ( P : = 0.002 ) and flare ( P : = 0.009 ) , conjunctival erythema ( P : = 0.010 ) , ciliary flush ( P : = 0.022 ) , photophobia ( P : = 0.027 ) , and pain ( P : = 0.043 ) . Five times as many patients were dropped from the study for lack of efficacy from the vehicle group ( 22/52 ) than from the ketorolac group ( 4/52 ; P : = 0.001 ) . Ketorolac was found to be equally as safe as vehicle in terms of adverse events , changes in visual acuity , intraocular pressure , and biomicroscopic and ophthalmoscopic variables . CONCLUSIONS Ketorolac tromethamine 0.5 % ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery , while being as safe as vehicle One hundred and seventy-eight patients undergoing uncomplicated cataract extraction with posterior chamber intraocular lens insertion completed a prospect i ve , r and omized , controlled trial of oral piroxicam in the prophylaxis of postoperative cystoid macular edema ( CME ) , with a 1-year follow up . The incidence of " visually significant " CME , the mean interval to onset following surgery , clinical severity , recurrence rate , and the time to achieve best corrected visual result were unaffected by a 17-day piroxicam course . Oral steroid CME treatment produced a rapid response , but could not be shown to change the ultimate visual results . High-performance liquid chromatography analysis of aqueous humor obtained at cataract surgery suggested that piroxicam 's pharmacokinetics might be a factor in this lack of response ; the large number of potential inflammatory mediators uninfluenced by cyclo-oxygenase inhibition also may implicate piroxicam pharmacodynamics Abstract We evaluated two topical cyclo‐oxygenase inhibitors ( COIs ) , 0.03 % flurbiprofen and 1 % indomethacin , for their ability to prevent pseudophakic cystoid macular edema ( CME ) . The study was a r and omized , doublemasked , vehicle‐controlled , parallel group , clinical trial for six months at eight sites in Canada and two in Germany . The study population consisted of 681 patients who had extracapsular cataract extraction and posterior chamber lens implantation . Flurbiprofen , indomethacin , or the vehicle was instilled into the eye four times daily for two days preoperatively and three months postoperatively . Results were measured by angiographic and clinical CME at visit 5 ( day 21–60 ) and visit 7 ( day 121–240 ) and by contrast sensitivity and Snellen visual acuity at all five postoperative visits . At visit 5 , the incidence of angiographic CME was comparable in the two COI treatment groups ( 16.8 % flurbiprofen , 12.4 % indomethacin ) and was significantly lower than in the vehicle group ( 32.2 % ) . The incidence of clinical CME was also significantly lower in the COI‐treated groups ( 10.7 % flurbiprofen , 9.6 % indomethacin ) than in the vehicle group ( 21.9 % ) . By visit 7 , the incidence of angiographic CME had declined to between 4 % and 8 % and the incidence of clinical CME was less than 2 % in all three groups . At visit 5 , contrast sensitivity scores were significantly worse in vehicle‐treated patients with angiographic CME than in those without CME , and Snellen visual acuity was one line worse in patients with CME . Flurbiprofen‐treated patients achieved good Snellen visual acuity ( better than 20/40 ) sooner than vehicle‐treated patients . The results suggest that angiographic evidence of CME is related to a clinical ly relevant decrease in visual function and that treatment with flurbiprofen or indomethacin reduces the incidence and severity of CME and the associated visual dysfunction in the early postoperative period Purpose : To evaluate the effectiveness of diclofenac eyedrops in reducing inflammation and the incidence of angiographic cystoid macular edema ( CME ) after cataract surgery and intraocular lens ( IOL ) implantation . Setting : Eye Clinic , Institute of Biomedical Sciences , San Paolo Hospital , Milan , Italy . Methods : Eighty‐eight patients having cataract extraction were enrolled in a r and omized clinical trial : 42 were given diclofenac eyedrops and 46 , placebo . Postoperative inflammation in both groups was grade d for 6 months using a dedicated system . Results : Eight patients ( 9 % ) had evidence of angiographic CME approximately 1 month after surgery ; seven of these were in the placebo group ( P = .039 ) . This difference was not significant 3 and 6 months postoperatively . The signs of ocular inflammation were greater in the eyes receiving placebo ; the difference was particularly evident up to 1 week after surgery . There was no significant difference in visual acuity between the two groups at any follow‐up point , but the contrast sensitivity of the eyes that received diclofenac improved significantly at 10.5 cycles per degree 1 month postoperatively . Conclusion : Diclofenac eyedrops effectively reduced ocular inflammation and the occurrence of angiographic CME after cataract surgery BACKGROUND To determine the incidence and risk factors for cystoid macular edema ( CME ) after phacoemulsification surgery and its effect on visual acuity . METHODS This prospect i ve study evaluated 98 eyes of 98 patients ( 43 women ) with a mean ( SD ) age of 61.8 ( 11.3 ) years . Phacoemulsification was performed with temporal clear corneal incision and implantation of foldable hydrophilic acrylic intraocular lens in the bag . Postoperative visits were on day 1 , week 1 , and at 1 , 3 , and 6 months . In addition , at week 10 all patients had fundus fluorescein angiography , and presence of CME was determined . Age , sex , iris colour , pseudoexfoliation , type of cataract , phaco time , status of the posterior vitreous , iris trauma , severity of anterior chamber reaction , and visual acuities were evaluated . RESULTS No major intraoperative complications occurred . Twenty-five ( 25.5 % ) eyes were CME(+ ) , and 73 ( 74.4 % ) eyes were CME(- ) . CME occurred in 70 % of patients with iris trauma and 20.5 % of patients with no iris trauma . CME was more common in patients who had postoperative anterior chamber inflammation of 2 + or more than in patients with less inflammation ( 43.2 % vs. 11.5 % ) . Complete posterior vitreous detachment had some apparent protective effect against CME development . The mean visual acuities of CME(+ ) patients were lower than those of CME(- ) patients in all postoperative periods . The difference was significant in the third month ( p < 0.05 ) . INTERPRETATION CME after phacoemulsification was associated with iris trauma and severe postoperative inflammation . Complete posterior vitreous detachment had some apparent protective effect against CME development . CME may be associated with decreased visual acuity Purpose : To evaluate the use of nepafenac 0.1 % in patients with cystoid macular edema who are known steroid responders . Methods : Patients ( N = 15 ) with clinical and angiographic cystoid macular edema ( ≥2 months ) and a history of increased intraocular pressure following administration of topical corticosteroids participated in this prospect i ve , open-label , pilot study . All patients were treated with nepafenac 0.1 % four times daily for 6 weeks and the dose was tapered off over the ensuing 6 weeks . The total treatment duration was 12 weeks . Visual acuity and retinal thickness were measured . Results : For the entire population , there was a mean significant improvement in visual acuity and retinal thickness at 4 weeks and 12 weeks posttreatment compared with baseline ( P < 0.0001 ) . A subgroup analysis revealed that patients with pseudophakic cystoid macular edema ( n = 11 ) had a mean significant improvement in visual acuity and retinal thickness compared with baseline at 4 weeks and 12 weeks posttreatment ( P < 0.0001 ) . Although the improvement in the vitreoretinal interface disorders group was not statistically different from baseline ( probably due to the outlier ) , three of the four patients with vitreoretinal interface disorders had improvement in visual acuity and retinal thickness . Nepafenac was well tolerated . Conclusion : Nepafenac may be an effective and safe therapy for treating chronic cystoid macular edema in patients who are steroid responders Various doses of a new topical nonsteroidal anti-inflammatory agent , diclofenac sodium , were tested against prednisolone sodium phosphate in a r and omized double-masked study to determine comparative efficacy and safety regarding the reduction of postsurgical ocular inflammation . Inflammation was assessed by measuring fluorescein leakage into the anterior chamber using fluorophotometry techniques . Increased leakage in each patient 's operated-on eye compared with the unoperated-on control eye was attributed to a breakdown in the blood-aqueous barrier caused by the cataract surgery . Elimination or significant reduction of fluorescein leakage within a treatment group constituted increased efficacy in controlling inflammation . A total of 124 cases were analyzed . There were no preoperative differences among groups in fluorescein leakage . At 1 week after surgery , all three diclofenac groups had significantly less fluorescein leakage compared with the prednisolone group . Mean percent increases were 56 % to 118 % in diclofenac groups vs 324 % in the prednisolone group . No differences among diclofenac concentrations were detected . The differences between prednisolone and diclofenac were also present , although of lesser magnitude , at 3 weeks . This demonstration of increased efficacy of the nonsteroidal anti-inflammatory agent vs prednisolone is promising given the known side effects of ocular steroids PURPOSE : To compare a topical nonsteroidal antiinflammatory drug ( nepafenac 0.1 % ) and a topical steroidal antiinflammatory drug ( fluorometholone 0.1 % ) in preventing cystoid macular edema ( CME ) and blood – aqueous barrier ( BAB ) disruption after small‐incision cataract extraction with foldable intraocular lens ( IOL ) implantation . SETTING : Shohzankai Medical Foundation , Miyake Eye Hospital , Nagoya , Japan . DESIGN : R and omized double‐masked single‐center clinical trial . METHODS : Patients were r and omized to receive nepafenac 0.1 % eyedrops or fluorometholone 0.1 % eyedrops for 5 weeks after phacoemulsification with foldable IOL implantation . The incidence and severity of CME were evaluated by fluorescein angiography , retinal foveal thickness on optical coherence tomography , and BAB disruption on laser flare – cell photometry . RESULTS : Thirty patients received nepafenac and 29 patients , fluorometholone . Five weeks postoperatively , the incidence of fluorescein angiographic CME was significantly lower in the nepafenac group ( 14.3 % ) than in the fluorometholone group ( 81.5 % ) ( P<.0001 ) . The fovea was thinner in the nepafenac group than in the fluorometholone group at 2 weeks ( P=.0266 ) and 5 weeks ( P=.0055 ) . At 1 , 2 , and 5 weeks , anterior chamber flare was significantly less in the nepafenac group than in the fluorometholone group ( P<.0001 , P<.0001 , and P=.0304 , respectively ) . The visual acuity recovery from baseline was significantly greater in the nepafenac group ( 80.0 % ) than in the fluorometholone group ( 55.2 % ) ( P=.0395 ) . There were no serious side effects in either group . CONCLUSION : Nepafenac was more effective than fluorometholone in preventing angiographic CME and BAB disruption , and results indicate nepafenac leads to more rapid visual recovery . Financial Disclosure : No author has a financial or proprietary interest in any material or method mentioned . Additional disclosures are found in the footnotes The effect of 1 % Indomethacine solution on the development of post-operative macular edema was examined . Starting from the day of the operation , the patients received 1 drop of either the solution or the placebo 4 times daily for 3 months . Using fluorescein angiography it was demonstrated that post-operative macular edema developed with a significantly lower incidence in patients treated with the prostagl and ine inhibitor Indomethacin than in the control group . There was no noticeable difference between the 2 groups with regard to side-effects PURPOSE : To compare the effectiveness of a topical nonsteroidal drug ( diclofenac 0.1 % ) and a topical steroidal drug ( betamethasone 0.1 % ) in preventing cystoid macular edema ( CME ) and blood – aqueous barrier ( BAB ) disruption after small‐incision cataract surgery and foldable intraocular lens ( IOL ) implantation . SETTING S : Shohzankai Medical Foundation Miyake Eye Hospital , Tokyo , Japan . METHODS : This multicenter interventional double‐masked r and omized study comprised 142 patients having phacoemulsification and foldable IOL implantation . Seventy‐one patients were r and omized to receive diclofenac eyedrops and 71 , betamethasone eyedrops for 8 weeks postoperatively . The incidence and severity of CME were evaluated by fluorescein angiography . Blood – aqueous barrier disruption was determined by laser flare – cell photometry . RESULTS : Of the patients , 63 were men and 79 were women . Five weeks after surgery , the incidence of fluorescein angiographic CME was lower in the diclofenac group ( 18.8 % ) than in the betamethasone group ( 58.0 % ) ( P<.001 ) . At 1 and 2 weeks , the amount of anterior chamber flare was statistically significantly less in the diclofenac group than in the betamethasone group ( P<.05 ) . At 8 weeks , intraocular pressure was statistically significantly higher in the betamethasone group ( P = .0003 ) . CONCLUSIONS : Diclofenac was more effective than betamethasone in preventing angiographic CME and BAB disruption after small‐incision cataract surgery . Thus , nonsteroidal antiinflammatory agents should be considered for routine treatment of eyes having cataract surgery Background / Aims : To evaluate the benefit of adding a nonsteroid agent to an antibiotic/steroid combination after uneventful phacoemulsification , adopting a weekly follow-up , to gain insight into the optimal duration of postoperative treatment and to examine whether risk factors for inflammation exist . Methods : Patients were r and omized to ( i ) tobramycin 0.3%-dexamethasone 0.1 % , 1 drop q.i.d . ( n = 72 ) , and ( ii ) a combination of tobramycin 0.3%-dexamethasone 0.1 % , 1 drop q.i.d . , plus ketorolac tromethamine 0.5 % , 1 drop t.i.d . ( n = 73 ) . On days 7 , 14 , 21 and 28 , the frequency of inflammation-related signs ( corneal edema , conjunctival hyperemia , anterior chamber or Tyndall reaction ) as well as best-corrected visual acuity ( BCVA ) were measured . On day 21 , logistic regression was performed to evaluate risk factors for inflammation . Results : The frequency of inflammation-related signs did not differ between the 2 groups at any time point , neither did BCVA . On day 21 , pseudoexfoliation was associated with the presence of any inflammation-related sign ( OR = 4.5 ; 95 % CI : 1.2–16.0 ; p = 0.022 ) . No evidence of clinical ly significant cystoid macular edema became evident in either group . Conclusion : The addition of ketorolac did not seem to offer any additional benefit in terms of inflammation-related signs . Four weeks appeared as an adequate treatment interval . Special attention should be paid to patients with pseudoexfoliation |
11,184 | 23,590,215 | Nasal inhalation of corticosteroids significantly improved morning and evening peak expiratory flow .
There were no significant changes in asthma outcomes with the addition of INCS spray to orally inhaled corticosteroids .
Thus , the results of this meta- analysis demonstrated that intranasal corticosteroid medications significantly improve some asthma-specific outcome measures in patients suffering from both AR and asthma .
This effect was most pronounced with INCS sprays when patients were not on orally inhaled corticosteroids , or when corticosteroid medications were inhaled through the nose into the lungs .
Overall , intranasal corticosteroid medications improve some asthma-specific outcome measures in patients with both AR and asthma . | Given the relationship between allergic rhinitis ( AR ) and asthma , it can be hypothesized that reducing inflammation in the upper airway with intranasal corticosteroid ( INCS ) medications may improve asthma outcomes .
The goal of this study was to perform a systematic review with meta- analysis of the efficacy of INCS medications on asthma outcomes in patients with AR and asthma . | During the ragweed season of 1984 we studied 120 patients with hay fever ; 58 had a history of asthma during the ragweed season the year before . They were divided into four treatment groups to receive nasal sprays of placebo , cromolyn sodium , flunisolide , or beclomethasone . In controlling hay fever symptoms all medications were superior to placebo ; the glucocorticoids were more effective than was cromolyn sodium . Chest symptoms in the 58 patients with a history of asthma were also relieved by the topical nasal treatment . Various explanations for the beneficial effect of topical nasal treatment in asthma symptoms are conceivable . We consider the most likely to be improvement of nasal airway function . With restoration of the filtering action of the nose , less allergen would penetrate to the intrathoracic airways because of reduction in mouth breathing Background Asthma and allergic rhinitis are the two most common chronic disorders in childhood and adolescence . To date , no study has examined the impact of comorbid allergic rhinitis on asthma control in children . Objective To examine the prevalence of allergic rhinitis in children with asthma , and the impact of the disease and its treatment on asthma control . Methods A cross-sectional survey in 203 children with asthma ( 5–18 years ) using vali date d question naires on rhinitis symptoms ( stuffy or runny nose outside a cold ) and its treatment , and the paediatric Asthma Control Question naire ( ACQ ) . Fraction of nitric oxide in exhaled air ( FeNO ) was measured with a Niox Mino analyser ; total and specific IgE levels were assessed by the Immunocap system . Results 157 children ( 76.2 % ) had symptoms of allergic rhinitis but only 88 of these ( 56.1 % ) had been diagnosed with the condition by a physician . ACQ scores were worse in children with allergic rhinitis than in those without the condition ( p=0.012 ) . An ACQ score ≥1.0 ( incomplete asthma control ) was significantly more likely in children with allergic rhinitis than in those without ( OR 2.74 , 95 % CI 1.28 to 5.91 , p=0.0081 ) , also after adjustment for FeNO levels and total serum IgE. After adjustment for nasal corticosteroid therapy , allergic rhinitis was no longer associated with incomplete asthma control ( OR 0.72 , 95 % CI 0.47 to 1.12 , p=0.150 ) . Conclusion Allergic rhinitis is common in children with asthma , and has a major impact on asthma control . The authors hypothesise that recognition and treatment of this condition with nasal corticosteroids may improve asthma control in children , but r and omised clinical trials are needed to test this hypothesis Introduction . Rhinitis and asthma are currently recognized as manifestations of a single syndrome , the chronic allergic respiratory syndrome . Nearly all individuals with asthma have rhinitis , and severe rhinitis has been associated with worse outcomes in asthma patients . Intranasal treatment has been reported to be beneficial for the lower airways . Methods . This was a r and omized , double-blind , placebo-controlled study . The objective was to evaluate the effects that treatment with intranasal beclomethasone dipropionate ( BDP ; 400 μ g/d ) has on nasal and bronchial symptoms , as well as on lung function test results and bronchial responsiveness to histamine in patients with allergic rhinitis and asthma . We evaluated 33 patients , divided into two groups : treatment ( n = 17 ) ; and placebo ( n = 16 ) . Over the course of the 125-day study period , each patient reported daily rhinitis and asthma symptoms , as well as the need for additional medication . All patients were su bmi tted to spirometry and histamine challenge at baseline and at each subsequent evaluation ( on days 50 and 75 ) . Results . In comparison with the patients in the placebo group , those in the BDP treatment group presented significantly fewer nasal symptoms on day 50 and fewer asthma symptoms on day 75 ( p < 0.01 for both ) ; required rescue medications less often ; and presented a significantly lower degree of bronchial responsiveness to histamine on day 75 ( p < 0.01 ) . Conclusion . In this study , intranasal BDP was effective in treating rhinitis as well as asthma . The benefits for the lower airways were observed only after prolonged treatment and might be better evaluated through nonspecific bronchial challenge BACKGROUND It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness ( BHR ) in asthmatic subjects with seasonal rhinitis . The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre ( forced expiratory volume in one second , FEV1 ) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons . METHODS In the first pollen season 25 patients aged 8–28 years were included in a double blind , placebo controlled study . The active treatment group used fluticasone aqueous spray 200 μg once daily . In the second pollen season 72 patients aged 8–28 years participated in a double blind , placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 μg twice daily was included . FEV1 was measured before and after three and six weeks of treatment ; BHR to methacholine ( PD20 ) was measured before and after six weeks of treatment . RESULTS In the first season the mean ( SD ) logPD20 of the patients decreased significantly both in the fluticasone group ( from 2.43 ( 0.8 ) μg to 1.86 ( 0.85 ) μg ) and in the placebo group ( from 2.41 ( 0.42 ) μg to 1.87 ( 0.78 ) μg ) without any intergroup difference in the change in logPD20 . In the second pollen season the mean logPD20 in the fluticasone , beclomethasone , and placebo groups did not change significantly . CONCLUSIONS Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a r and omized , double-blind , placebo-controlled , crossover study . Twenty-one young patients with perennial allergic rhinitis and asthma , with documented lower airway hyperresponsiveness ( PC20 methacholine < 8 mg/ml ) , were treated with intranasal aqueous beclomethasone dipropionate and placebo , each given for 4 weeks . Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening . Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment . PC20 methacholine was performed at baseline and at the end of each treatment period . Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores ( p = 0.05 ) after 4 weeks of treatment . Global asthma scores did not change significantly ( p = 0.2 ) . Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone , but not after placebo ( p = 0.04 ) . Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment , but carryover effect of steroids precluded comparative analysis of the second 4-week block ( morning p = 0.06 , evening p = 0.03 ) . Morning asthma scores tended to decrease ( p = 0.07 ) . Evening asthma scores were significantly decreased at weeks 2 and 3 ( p = 0.001 , p = 0.02 , respectively ) . No change in peak expiratory flow rate was seen . This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity . Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment Background Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms . Leukotriene antagonists may therefore be an alternative to corticosteroid therapy To test the hypothesis that nasal antiinflammatory treatment can modify both upper and lower airway responses to allergen exposure , 12 cat-allergic subjects underwent 1 h cat exposure challenges at baseline , with nasal occlusion , and after 1 wk of treatment with either intranasal triamcinolone acetonide or placebo in a double-blind crossover trial . Challenges were performed in a room containing two cats with airborne Fel d I levels ranging from 35 to 37,525 ng/m3 . Overall , nasal symptoms were moderately reduced by treatment ( p = 0.06 ) , with the greatest reduction occurring in the first 15 and 30 min of the challenge ( p < 0.01 and p < 0.05 , respectively ) . Mean lower respiratory symptoms were also diminished by treatment ( p = 0.02 ) , although those effects were most evident during the last 15 min of the challenge . Maximum changes in FEV1 were slightly reduced by the nasal therapy ( p = 0.07 ) , reaching statistical significance only at the 30-min intervals ( p < 0.05 ) . There were no significant differences in nasal histamine or TAME esterase levels . When challenges were repeated with nasal occlusion , no significant differences were detected in chest symptoms or FEV1 changes . We conclude that treatment with an intranasal corticosteroid led to significant reductions in both upper and lower airway responses to intense cat exposure BACKGROUND Allergic rhinitis ( AR ) and asthma are commonly associated , and similar underlying inflammatory processes link both diseases . AR , even in the absence of asthma , is associated with increased levels of exhaled nitric oxide ( ENO ) and hydrogen peroxide ( H(2)O(2 ) ) in exhaled breath condensate , 2 noninvasive markers of lower airway inflammation . OBJECTIVE We sought to evaluate the effect of treatment with the nasal steroid triamcinolone acetonide on ENO and exhaled H(2)O(2 ) in subjects with AR . METHODS We allocated 23 subjects in a r and omized , double-blind , parallel-controlled fashion to 4-week treatment with triamcinolone acetonide ( 220 microg/d ) or matching placebo . RESULTS ENO levels were greater in the subgroup with concomitant asthma ( 16/23 subjects ) and decreased significantly with triamcinolone acetonide treatment in this subgroup of patients in comparison with patients receiving placebo . Breath condensate levels of H(2)O(2 ) were higher in patients with AR without asthma than in those with asthma but decreased significantly with triamcinolone acetonide treatment in both subgroups . No changes were observed in bronchial hyperresponsiveness , nasal and asthma symptoms , or peak expiratory flow with active treatment or placebo . CONCLUSION We conclude that treatment of AR with triamcinolone acetonide results in decrease of 2 noninvasive markers of lower airway inflammation , ENO and H(2)O(2 ) , supporting that upper and lower airway inflammation should be seen as a continuum in subjects with AR with and without asthma . ENO might be a more specific marker of the lower airway inflammation present in asthma RATIONALE Allergic rhinitis and exercise induced bronchoconstriction ( EIB ) are common in asthmatic children . The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children . METHODS This was a double-blind , r and omized , placebo-controlled , parallel group study . Subjects aged 12 - 17 years , with mild-to-moderate asthma , intermittent allergic rhinitis and ≥ 10 % fall in FEV(1 ) at a screening exercise challenge were r and omized to 22 ± 3 days treatment with intranasal fluticasone furoate or placebo . The primary outcome was change in exercise induced fall in FEV(1 ) . Secondary outcomes were changes in the area under the curve ( AUC ) , asthma control question naire ( ACQ ) , pediatric asthma quality of life question naire ( PAQLQ ) , and exhaled nitric oxide ( FeNO ) . RESULTS Twenty-five children completed the study . Mean exercise induced fall in FEV(1 ) ( ± SD ) decreased significantly ( 95 % CI : 0.7 - 18.2 % , P = 0.04 ) in the fluticasone furoate group from 28.4 ± 15.8 % to 19.0 ± 13.8 % , compared to the placebo group ( 27.4 ± 16.0 % to 27.4 ± 19.2 % ) . The change in AUC was not significantly different between treatment groups . However , within the fluticasone furoate group the AUC decreased significantly ( P = 0.01 ) . Although total PAQLQ score did not improve , the activity limitation domain score improved significantly within the fluticasone furoate group ( P = 0.03 ) . No significant changes were observed in FeNO and ACQ . CONCLUSION Treatment of allergic rhinitis in asthmatic children with an intranasal corticosteroid reduces EIB and tends to improve quality of life Allergic rhinitis ( AR ) and asthma coexist frequently and a dual treatment is recommended by prescribing topical nasal plus oral inhaled corticosteroids . The purpose of this study was to assess the efficacy of a nasally inhaled corticosteroid aim ing at concomitant control of AR and asthma . A controlled trial was conducted among 60 patients with AR and asthma , aged 6–18 years , who were r and omized into two groups . During 8 weeks , the experimental group ( 30 patients ) received exclusively fluticasone propionate hydrofluoroalkane ( FP‐HFA ) inhaled through the nose ( mouth closed ) using a large volume spacer attached to a face mask . The comparison group ( 30 patients ) received a nasal spray of isotonic saline plus oral inhalation of FP‐HFA through a mouthpiece attached to the same spacer . Clinical scores for AR and asthma , nasal inspiratory peak flow ( NIPF ) , and spirometry were assessed by blinded observers . There was a significant improvement in AR scores and NIPF in the experimental group ( P ≤ 0.01 ) up to week 8 , when a worsening was observed after the intervention was interrupted . Asthma symptoms score , forced expiratory volume (FEV)1 , and FEF25−75 % were not statistically different between groups at the baseline visit or along follow‐up visits ( P ≥ 0.20 ) . Prebronchodilator FEV1 ( % predicted value ) improved by 10 % in both groups , comparing values at inclusion with those obtained at the end of follow up . Our results suggest that nasally inhaled FP‐HFA through a spacer may control AR and asthma in children and adolescents . This approach is likely to result in higher compliance , lower costs , and fewer side effects BACKGROUND Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients . OBJECTIVE To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis ( SAR ) and persistent asthma . METHODS A total of 863 patients ( mean baseline FEV1 81 % predicted ) were r and omized to receive open-label fluticasone propionate/salmeterol ( FSC ) , 100/50 microg bid for 4 weeks , plus either blinded fluticasone propionate aqueous nasal spray ( FPANS ) 200 microg/d , montelukast 10 mg/d , or placebo . Patients kept daily records of peak expiratory flow ( PEF ) , asthma , and rhinitis symptoms and rescue albuterol use . RESULTS FPANS added to FSC result ed in superior outcomes for daytime total nasal symptom scores ( D-TNSS ) and individual daytime nasal specific symptoms ( congestion , rhinorrhea , sneezing , and itching ) compared with montelukast plus FSC and placebo plus FSC ( p < or = 0.001 ) . Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing . Morning PEF , asthma symptoms , and rescue albuterol use improved significantly ( p < or = 0.001 ) in all treatment groups , but improvements were comparable across the treatment groups . CONCLUSION In patients with persistent asthma treated with FSC , the addition of montelukast or FPANS for the treatment of SAR result ed in no additional improvements in overall asthma control compared with FSC alone . However , FPANS provided superior rhinitis control compared with montelukast . These data suggest that asthma and rhinitis should each be optimally treated The effect of intranasally administered corticosteroid ( budesonide ) on nasal symptoms , mode of respiration ( nasal versus mouth breathing ) , and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction . After a 2-wk run-in period , the children were allocated r and omly to 4 wk of intranasal therapy with either budesonide ( 400 micrograms/day ) or placebo spray . A double-blind , parallel design was used . Diaries for peak expiratory flow , asthma , and rhinitis symptom scores and degree of mouth breathing were recorded at home . Nasal eosinophilia , nasal airway resistance at a flow of 0.2 L/s ( NAR0.2 ) , and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment . Budesonide , when compared with placebo , significantly decreased nasal obstruction ( p less than 0.05 ) , secretion ( p less than 0.01 ) , and eosinophilia ( p less than 0.02 ) , as well as NAR0.2 ( p less than 0.05 ) and mouth breathing ( p less than 0.01 ) . The improvement in nasal obstruction correlated closely to the changes in mouth breathing ( r = 0.80 , n = 17 , p less than 0.001 ) . Furthermore , intranasally administered budesonide result ed in less exercise-induced asthma ( EIA ) ( p less than 0.02 ) and decreased cough and asthma severity significantly . Pulmonary mechanics were only marginally improved . The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis . An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity , but the results gave no clear evidence of an association between nasal airway function and asthma BACKGROUND Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines . This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device ( Opt-Powder ; OptiNose US Inc. , Yardley , PA , USA ) to that of liquid aerosol administered via a traditional h and -actuated liquid spray pump ( Rexam SP270 , Rexam Pharma , France ) . METHODS The study was an open-label , crossover design in seven healthy subjects ( five females , two males ) . The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either (99m)Tc-labeled lactose powder or liquid (99m)Tc- diethelyne triamine pentaacetic acid-aerosol . The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions . Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated . RESULTS Both powder and spray were distributed to all of the nasal regions . The Opt-Powder device , however , achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray ( upper posterior region ; Opt-Powder 18.3 % ± 11.5 vs. Spray 2.4 % ± 1.8 , p<0.02 ; sum of upper and middle posterior regions ; Opt-Powder 53.5 % ± 18.5 vs. Spray 15.7 % ± 13.8 , p<0.02 ) . The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder ( Opt-Powder 17.4 % ± 24.5 vs. Spray 59.4 % ± 18.2 , p<0.04 ) . OptiNose powder delivery result ed in more rapid overall nasal clearance . No lung deposition was observed . CONCLUSIONS The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions , whereas less was deposited in the lower regions . Overall nasal clearance of powder was slower initially , but due to retention in anterior nonciliated regions the overall nasal clearance after spray was slower BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of allergic rhinitis . Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma Glucorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma . This therapy is highly effective , and side effects are few and mild . It was the aim of the present study to evaluate a physiological nasal inhalation technique , which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles . Thirty adults with grass pollen‐induced rhinitis and asthma inhaled the steroid molectile budesonide through the nose from a pressurized aerosol attached to a spacer device . Compared with inhalation of placebo , the treatment result ed in a significant reduction of nasal symptoms ( P=0.005 ) , of bronchial symptoms ( P=0.005 ) , bat not of eye symptoms . In addition , nasal peak inspiratory flow ( P=0.0003 ) and oral peak expiratory flow ( P=0.02 ) increased . There was no difference between budesonide and placebo with regard to local side effects , such as nose bleeding , hoarseness , and irritation in mouth and throat . It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects . This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma , especially when conventionel spray therapy is associated with local side effects Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness ( BR ) . To assess the clinical relevance of these experimental changes to chronic asthma , we sought to determine the effect of nasal beclomethasone dipropionate ( Bdp ) on BR in patients with seasonal allergic rhinitis and asthma . Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp ( 336 micrograms/day ) or placebo for the entire ragweed season . Patients recorded daily nasal and chest symptoms , nasal blockage index , oral peak expiratory flow rates , and supplemental medication use . BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season . Although the Bdp group did have a significant improvement in nasal blockage index , there was no improvement in daily asthma symptom scores , oral peak expiratory flow , or asthma medication use . However , subjects treated with Bdp were protected from the increase in BR seen in the placebo group ( geometric mean PC20 placebo group : baseline = 0.70 , week 6 = 0.29 ; Bdp group : baseline = 0.80 , week 6 = 0.93 ; intergroup difference , p = 0.022 ) . We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma Background : Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma . We investigated the effect of intranasal , inhaled corticosteroid or the combination of both in patients with both pollen‐induced rhinitis and asthma The st and ard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth . Although this therapy is highly effective , and side‐effects are few and mild , it may be possible further to improve the therapeutic index and patient compliance with the treatment . In the present study , we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma . In principle , it results in an airway deposition of the corticosteroid similar to that of inhaled allergens . Twenty‐four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol , attached to a spacer device , in a double‐blind , placebo‐controlled , crossover study . Compared with placebo , budesonide treatment result ed in a significant reduction of nasal symptoms ( P<0.01 ) and of asthma symptoms ( P<0.05 ) , and in an increase of nasal peak inspiratory flow ( P<0.001 ) and of oral peak expiratory flow ( P=0.01 ) . There were no differences between budesonide and placebo in local side‐effects , such as dry nose , nosebleed , and hoarseness . We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children , but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side‐effects Asthma and allergic rhinitis ( AR ) form a well-recognized comorbidity . This study aims at assessing the efficacy of nasally inhaled beclomethasone dipropionate ( BDP ) in their simultaneous treatment . A r and omized controlled trial was conducted with 78 allergic rhinitis and asthma patients aged 5 - 17 years . Seventy-five individuals completed the study . During 8 weeks , 38 subjects received BDP-CFC aerosol ( > or= 500 mcg/day ) exclusively via nasal inhalation through a facemask attached to a plastic valved spacer . The control group ( 37 patients ) received 200 mcg/day of aqueous intranasal beclomethasone plus oral inhalation of BDP-CFC ( > or= 500 mcg/day ) through a mouthpiece connected to the same spacer . Primary outcomes analyzed in order to assess the response to treatment were clinical scoring for allergic rhinitis and measurements of nasal inspiratory peak flow ( NIPF ) . AR clinical scoring and NIPF did not differ in the two groups at admission or at nearly all follow-up visits . Nasal inhalation of beclomethasone dipropionate provides AR symptom relief while maintaining control of asthma by delivering it to the lungs . Therefore , this therapeutic strategy might be considered for patients suffering from this comorbidity , especially in low-re source countries , since it is less expensive than the conventional treatment Rhinitis is common in asthmatic schoolchildren who are allergic to animal d and er and constantly and indirectly exposed to these allergens in their everyday environment . As a patho-physiological linkage between nasal and bronchial inflammation has been proposed to exist , the primary objective of this study was to determine whether nasal administration of mometasone furoate ( MSNF ) can reduce bronchial inflammation , as reflected in the level of exhaled nitric oxide ( F(E)NO ) in asthmatic schoolchildren with d and er allergy and mild-to-moderate rhinitis . Forty such children were assigned r and omly to be treated for 4 wk with MSNF or placebo , employing a double-blind procedure . F(E)NO was the primary end-point measured and secondary end-points were nasal levels of NO , the concentration of eosinophilic cationic protein ( ECP ) in nasal lavage , the relative numbers of eosinophils in blood , forced expiratory volume in 1 s ( FEV(1 ) ) , peak expiratory flow ( PEF ) and scoring of symptoms . There was no significant difference in the F(E)NO values of the treated and control groups at any time-point , whereas the nasal level of ECP was lower in the treated group compared with placebo ( p = 0.05 ) on both days 7 and 28 , and compared with baseline for the treated group ( p = 0.06 on day 7 , p = 0.02 on day 28 ) . Furthermore , the mean blood eosinophil count decreased in the treated group , which also demonstrated lower scores for nasal symptoms compared with placebo , but neither of these differences were statistically significant . FEV(1 ) , PEF and nasal levels of NO remained unchanged in both groups . Four weeks of nasal treatment with MSNF had no effect on bronchial inflammation , as reflected by exhaled NO , whereas signs of nasal and systemic eosinophil activation were reduced . Thus , nasal administration of a steroid as a strategy to reduce asthmatic inflammation remains question able in mild-to-moderately severe cases of perennial rhinitis and asthma Limited information exists comparing fluticasone propionate/salmeterol combination ( FSC ) versus montelukast ( MON ) in patients with coexistent asthma and allergic rhinitis . The purpose of this study was to compare the addition of MON to patients receiving FSC on asthma control while experiencing asthma and allergy symptoms . Additionally , the effect of fluticasone propionate aqueous nasal spray ( FPANS ) and MON were assessed in allergic rhinitis control . Symptomatic patients ( n = 1385 ) with asthma and seasonal allergic rhinitis were r and omized to receive FSC , 100/50 micrograms twice daily ; FSC twice daily + FPANS , 200 micrograms once daily ; FSC twice daily + MON , 10 mg once daily ; or MON once daily for 4 weeks during the allergy pollen season . Patients recorded peak expiratory flow , rescue albuterol use , and asthma and rhinitis symptoms . No additional improvements in overall asthma control were seen when MON was added to FSC . Treatment with FSC produced significant ( p < 0.001 ) improvements in all clinical and patient-reported measures versus MON . FSC + FPANS was superior to FSC + MON ( p < or = 0.001 ) in improving daytime and nighttime total nasal symptom scores . Adverse events were similar . In patients with asthma and allergic rhinitis , adding MON to FSC provided no additional benefit in asthma control . FSC result ed in superior improvement in asthma control compared with MON . FPANS also provided superior nasal symptom control versus MON in allergic patients treated with FSC for asthma . Optimal disease control in patients with asthma and allergic rhinitis should be achieved by the most effective therapy directed toward each disease component Background . The mechanisms through which rhinitis affects asthma have not been completely eluci date d. We explored whether the effect of nasal treatment on asthma control and respiratory-related quality of life ( HRQoL ) is mediated by inflammatory changes of the upper and lower airways . Methods . Allergic rhinitics with mild asthma were r and omized to a 14-day treatment period with either nasal budesonide 100 μg , 1 puff per nostril twice a day , or placebo . Clinical , functional , and biological evaluations were performed before and after treatment . Results . Twenty subjects ( M/F : 10/10 ; age : 31 ± 15 years ; mean ± SD ) were enrolled , and a total of 17 individuals completely participated in the study . Lung function was within the normal range . The total asthma control test ( ACT ) score was 20 ± 5.3 and the RHINASTHMA Global Summary ( GS ) was 44 ± 15 . The percentage proportion of eosinophils in nasal lavage was 9.9 % and significantly correlated with spirometric parameters reflecting peripheral airway function ( for FEF50 : r = 0.48 , p = .03 ; for FEF25 : r = 0.47 , p = .03 ) . The pH of the exhaled breath condensate ( EBC ) was 7.33 ± 0.4 . After nasal treatment , the percentage proportion of eosinophils fell significantly ( p = .002 ) , and changes in percentage proportion of eosinophils were associated with changes both in the ACT score ( r = 0.76 , p = .04 ) and in the RHINASTHMA GS ( r = 0.77 , p = .02 ) . The increase in the pH of the EBC was not associated with changes in the ACT score or with the RHINASTHMA GS . Conclusions . These findings confirm that , in subjects with allergic rhinitis with mild asthma , nasal inflammation impacts on asthma control and HRQoL. The improved control of respiratory symptoms obtained with nasal corticosteroids seems to be mediated by functional changes in the peripheral airways |
11,185 | 27,388,487 | Conclusions There appears to be a fair accuracy of FENO for making the diagnosis of asthma .
The overall specificity was higher than sensitivity , which indicates a higher diagnostic potential for ruling in than for ruling out the diagnosis of asthma | Background Measurement of FENO might substitute bronchial provocation for diagnosing asthma .
We aim ed to investigate the diagnostic accuracy of FENO measurement compared with established reference st and ard . | Background To evaluate the sensitivity , specificity and predictive values of fractional exhaled nitric oxide ( FENO ) for the diagnosis of asthma in general practice . Methods Prospect i ve diagnostic study with 160 patients attending 10 general practice s for the first time with complaints suspicious of obstructive airway disease ( OAD ) . Patients were referred to a lung function laboratory for diagnostic investigation . The index test was FENO measured with a portable FENO analyser based on electrochemical sensor . The reference st and ard was the Tiffeneau ratio ( FEV1/VC ) as received by spirometric manoeuvre and /or results of bronchial provocation . Bronchial provocation with methacholine was performed to determine bronchial hyper-responsiveness ( BHR ) in the event of inconclusive spirometric results . Results 88 ( 55 % ) were female ; their average age was 43.9 years . 75 ( 46.9 % ) patients had asthma , 25 ( 15.6 % ) had COPD , 8 ( 5.0 % ) had an overlap of COPD and asthma , and 52 ( 32.5 % ) had no OAD . At a cut-off level of 46 parts per billion ( ppb ) ( n = 30 ; 18.8 % ) , sensitivity was 32 % ( 95%CI 23–43 % ) , specificity 93 % ( 95%CI 85–97 % ) , positive predictive value ( PPV ) 80 % ( 95%CI 63–91 % ) , negative predictive value ( NPV ) 61 % ( 95%CI 52–69 % ) when compared with a 20 % fall in FEV1 from the baseline value ( PC20 ) after inhaling methacholine concentration ≤ 16 mg/ml . At 76 ppb ( n = 11 ; 6.9 % ) specificity was 100 % ( 95%CI 96–100 % ) and PPV was 100 % ( 95%CI 72–100 ) . At a cut-off level of 12 ppb ( n = 34 ; 21.3 % ) , sensitivity was 90 % ( 95%CI 79–95 % ) , specificity 25 % ( 95%CI 17–34 % ) , PPV 40 % ( 95%CI 32–50 ) , NPV 81 % ( 95%CI 64–91 % ) when compared with a 20 % fall of FEV1 after inhaling methacholine concentration ≤ 4 mg/ml . Three patients with unsuspicious spirometric results have to be tested with FENO to save one bronchial provocation test . Conclusion Asthma could be ruled in with FENO > 46 ppb . Mild and moderate to severe asthma could be ruled out with FENO ≤ 12 ppb . FENO measurement with an electrochemical sensor might be reasonable with respect to the time consuming procedure of bronchial provocation , which carries also some risk of severe bronchospasm . Further research is necessary to evaluate the effectiveness of this dual diagnostic strategy . The number needed to diagnose might be improved when the diagnostic precision could be enhanced by future technical developments BACKGROUND Assessing bronchial hyper-responsiveness ( BHR ) is a main diagnostic criterion of asthma . Provocation testing is not readily available in general practice , but peak expiratory flow ( PEF ) is . Several guidelines promote the use of PEF variability as a diagnostic tool for BHR . This study tested the agreement between histamine challenge testing and PEF variability , and the consequences for diagnosing asthma . AIM To investigate the possibility of assessing BHR by PEF variability , using a histamine provocation test as a reference . METHOD Subjects with signs of symptoms indicating asthma ( persistent or recurrent respiratory symptoms or signs of reversible bronchial obstruction ) ( n = 323 ) were studied . They had been identified in a population screening for asthma . A histamine provocation test and PEF variability were assessed over a three-week period . Asthma was defined as signs or symptoms together with a reversible airflow obstruction or BHR to the histamine challenge test . BHR was defined as a PC20 histamine of < or = 8 mg/ml or a PEF variability of > or = 15 % . Overall correlation between PC20 and PEF variability was calculated using Spearman 's rho . Furthermore , a decision tree was constructed to clarify the role of BHR in diagnosing asthma . RESULTS Thirty-two patients had a reversibility in forced expiratory volume in 1 second ( FEV1 ) of > or = 9 % predicted , 131 patients showed a PC20 of < or = 8 and 11 patients had a PEF variability of > or = 15 % . Overall correlation was poor at only -0.27 ( P < 0.0001 ) . One hundred and fourteen of the 131 patients diagnosed as having asthma when the histamine challenge test was used were not diagnosed by PEF variability . CONCLUSION PEF variability can not replace bronchial provocation testing in assessing BHR . This indicates that PEF variability and bronchial provocation do not measure the same aspects of BHR . If BHR testing is required in diagnosing asthma , a bronchial provocation test has to be used in general practice as well In athletes , exercise‐induced respiratory symptoms are common and their assessment is time and re source consuming . BACKGROUND Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability . Airway inflammation measured by fractional exhaled nitric oxide , measured at a flow rate of 50 ml/s ( FE(NO50 ) ) remains a controversial diagnostic tool . AIM To assess the ability of FE(NO50 ) to identify bronchial hyperresponsiveness ( BHR ) to methacholine ( provocative concentration of methacholine causing a 20 % fall in FEV(1 ) ; PC20 M ≤ 16 mg/ml ) and to establish whether or not symptoms relate to FE(NO50 ) and PC20 M in patients with no demonstrated reversibility to β(2 ) -agonist . METHODS We conducted a prospect i ve study on 174 steroid naive patients with respiratory symptoms , forced expiratory volume in 1 s ( FEV(1 ) ) ≥ 70 % predicted and no demonstrated reversibility to β(2 ) -agonist . Patients answered to a st and ardised symptom question naire and underwent FE(NO50 ) and methacholine challenge . Receiver-operating characteristic ( ROC ) curve and logistic regression analysis assessed the relationship between PC20 M and FE(NO50 ) , taking into account covariates ( smoking , atopy , age , gender and FEV(1 ) ) . RESULTS A total of 82 patients had a PC20 M ≤ 16 mg/ml and had significantly higher FE(NO50 ) ( 19 ppb vs. 15 ppb ; p < 0.05 ) . By constructing ROC curve , we found that FE(NO50 ) cut-off value of 34 ppb was able to identify not only BHR with high specificity ( 95 % ) and positive predictive value ( 88 % ) but low sensitivity ( 35 % ) and negative predictive value ( 62 % ) . When combining all variables into the logistic model , FE(NO50 ) ( p = 0.0011 ) and FEV(1 ) ( p < 0.0001 ) were independent predictors of BHR whereas age , gender , smoking and atopy had no influence . The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50 ) ( p < 0.001 and p < 0.05 , respectively ) . CONCLUSION The value of FE(NO50 ) > 34 ppb has high predictive value of PC20 M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated . However , FE(NO50 ) ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge INTRODUCTION Exercise-induced bronchoconstriction ( EIB ) is present in 40 to 90 % of patients with asthma . Exhaled NO ( eNO ) levels have been correlated with bronchial hyperresponsiveness to methacholine , and have correlated with the degree of decrease in FEV(1 ) with exercise . The purpose of our study was to examine whether eNO measurements prior to or after exercise could be used as a surrogate marker of exertional bronchoconstriction in a population referred specifically for the evaluation of EIB . METHODS We studied 50 consecutive subjects without a history of asthma who were referred for the clinical evaluation of EIB . eNO levels were measured prior to exercise challenge and every 5 min for a total of 30 min after exercise . Forced expiratory flows were measured prior to and serially after exercise challenge . RESULTS Seven subjects had a decrease in FEV(1 ) of > or = 15 % with exercise . The mean eNO level prior to exercise was 41 parts per billion ( ppb ) [ median + /- SD , 23 + /- 42.2 ppb ] in the EIB group and 25.6 ppb ( median , 19.95 + /- 18.47 ppb ) in the group without EIB . A receiver operator characteristic curve yielded a value of 0.636 . When using an eNO level of < 12 ppb , the sensitivity , specificity , negative predictive value , and positive predictive value for EIB were 1.0 , 0.31 , 0.19 , and 1.0 , respectively ; therefore , no one with a baseline eNO of < 12 ppb demonstrated EIB . CONCLUSIONS No subjects with very low pre-exercise eNO levels ( < 12 ppb ) demonstrated bronchial hyperresponsiveness to exercise . eNO measurement may obviate the need for bronchoprovocation testing in patients who complain of exertional dyspnea BACKGROUND Whole-body plethysmography ( WBP ) with bronchial challenge testing to measure the ( specific ) airway resistance , (s)R(AW ) , is considered to be a more sensitive diagnostic procedure than spirometry , which can only measure the forced expiratory volume in one second ( FEV1 ) . The evidence for the added diagnostic value of WBP is not yet conclusive . METHODS In a prospect i ve diagnostic study , we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011 . The bronchial provocation test was considered positive if the FEV1 fell by at least 20 % and /or the airway resistance doubled , with an increase of the sR(AW ) to at least 2.0 kPA × s and /or of the R(AW ) to 0.5 kPA × s/L. Follow-up evaluation was performed one year later . RESULTS The prevalence of asthma in the 302 patients who completed follow-up was 27.5 % . The sensitivity of WBP with sR(AW ) measurement for asthma was 95.2 % ( 95 % confidence interval [ CI ] 88.3%-98.1 % ) , and its specificity was 81.7 % ( 95 % CI 76.1%-86.3 % ) . The sensitivity of FEV1 was 44.6 % ( 95 % CI 34.4%-55.3 % ) , and its specificity was 91.3 % ( 95 % CI 86.6%-94.4 % ) . The negative predictive value ( NPV ) of WBP with sR(AW ) measurement was 97.8 % ( 95 % CI 94.5%-99.1 % ) , while that of FEV1 was 81.3 % ( 95 % CI 76.0%-85.7 % ) . The positive predictive value ( PPV ) of WBP with sR(AW ) measurement was 66.4 % ( 95 % CI 57.5%-74.2 % ) , while that of FEV1 was 66.1 % ( 95 % CI 53.0%-77.1 % ) . CONCLUSION With sR(AW ) measurement , asthma can be ruled out with high certainty . Improving the positive predictive value of testing for asthma remains a challenge , however , as sR(AW ) measurement does not yield any increase in specificity BACKGROUND The fraction of exhaled NO ( FeNO ) is valuable for the follow-up of asthmatic patients . However , its usefulness as a screening tool for asthma is not established . METHODS We screened a population of 961 university students with a modified European Community Respiratory Health Survey question naire that has been previously used for the screening of respiratory symptoms related to asthma . All subjects with a positive answer to at least one question ( n = 149 ) were su bmi tted to FeNO measurement with a portable nitric oxide analyzer . Subsequently , they were su bmi tted to spirometry and evaluated by a physician blinded to FeNO measurements . Seventy students with no respiratory symptoms served as control subjects . RESULTS Asthma was diagnosed in 63 subjects , and allergic rhinitis was diagnosed in 57 subjects . Asthmatics presented higher FeNO values than control subjects ( median , 20 parts per billion [ ppb ] ; interquartile range , 14 to 31 ppb ; vs median , 11 ppb ; interquartile range , 7 to 13 ppb , respectively ; p < 0.0001 ) , whereas they did not differ from patients with allergic rhinitis ( median , 17 ppb ; interquartile range , 12 to 23 ppb ; p = 0.28 ) . FeNO values > 19 ppb presented 85.2 % specificity and 52.4 % sensitivity for the diagnosis of asthma ( area under the curve [ AUC ] , 0.723 ) . The diagnostic performance of FeNO was better in nonsmokers ( AUC , 0.805 ) , yet FeNO values > 25 ppb were characterized by specificity > 90 % for the diagnosis of asthma both in smokers and in nonsmokers . However , FeNO was not a good marker for the differentiation between asthma and allergic rhinitis . CONCLUSIONS FeNO measurement with a portable analyzer is useful for the screening for asthma in young adults . Significant confounding factors are allergic rhinitis and current smoking BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects OBJECTIVES To determine the diagnostic accuracy of fractional exhaled nitric oxide ( FENO ) measurement in pneumologists routine diagnostic work-up ; and to determine the impact of the inflammatory pattern on diagnostic accuracy . METHODS Prospect i ve diagnostic study in 393 patients attending a private practice of pneumologists with complaints suspicious of obstructive airway disease ( OAD ) . Index test was FENO measurement . Reference st and ard was the Tiffeneau ratio ( FEV(1)/VC ) or airway resistance as assessed by whole body plethysmography , with additional bronchoprovocation or bronchodilator testing . Morning sputum was analysed with smear slides which were prepared and stained by Giemsa . RESULTS 154 patients were diagnosed as having asthma ( 145 diagnoses based on bronchial provocation , 9 based on bronchodilator results ) , 5 had COPD . For the whole group , asthma could be ruled in at FENO > 71 ppb ( PPV 80 % ; 95 % CI 63 - 90 % ) and ruled out at FENO ≤ 9 ppb ( NPV 82 % ; 95 % CI 67 - 91 % ) ( area under the curve ( AUC ) = 0.656 ; 95 % CI 0.600 - 0.712 ; p < 0.001 ) . 128 patients delivered sputum . FENO was 44.3 ppb ( sd 48.9 ) in patients with predominant eosinophilic inflammation , 18.5 ppb with neutrophilic inflammation , and 23.1 ppb in others ( p = 0.003 ) . Diagnostic accuracy of FENO increased when patients with neutrophilic inflammation were omitted from analysis ( AUC = 0.745 ; 95 % CI 0.651 - 0.838 ; p < 0.001 ) . Then asthma could be ruled in at FENO > 31 ppb ( PPV 82 % ; 95 % CI 63 - 92 % ) and ruled out at FENO ≤ 12 ppb ( NPV 81 % ; 95 % CI 62 - 91 % ) . CONCLUSIONS FENO measurement can be useful as an additional diagnostic tool in pneumologists ' practice . The diagnostic value of FENO could be improved when inflammatory patterns are taken into account RATIONALE The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy . To date , this has required undertaking a " trial of steroid " to identify responders . There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation , and this can be assessed indirectly using exhaled nitric oxide ( FENO ) measurements . OBJECTIVES We aim ed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind , fixed-sequence , placebo-controlled trial of inhaled fluticasone for 4 weeks . METHODS Comparisons of predictive accuracy were made between FENO and other conventional predictors : peak flows , spirometry , bronchodilator response , and airway hyperresponsiveness measured at baseline . " Steroid response " was defined as change in symptoms , peak flows , spirometry , or airway hyperresponsiveness to adenosine based on established guidelines and recommendations . RESULTS Steroid response was significantly greater in the highest FENO tertile ( > 47 ppb ) for each endpoint . This outcome was independent of the diagnostic label . The predictive values for FENO were significantly greater than for almost all other baseline predictors , with an optimum cut point of 47 ppb . CONCLUSIONS FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms . Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy BACKGROUND The fraction of nitric oxide in exhaled air ( FeNO ) is used in asthma diagnosis and management . Smoking reduces FeNO and 20 - 35 % of asthmatics are smoking . However no guidelines exist on the diagnostic value of FeNO in smokers . Therefore we assessed the value of FeNO to diagnose asthma in a population of subjects with asthma-like symptoms and different smoking habits . METHODS Measurements of FeNO , lung function , bronchial responsiveness and allergy testing were performed in 282 subjects ( 108 never- , 62 ex- and 112 current smokers ) aged 14 - 44 years , with symptoms suggestive of asthma . These subjects were a subset of subjects reporting respiratory symptoms ( n = 686 ) in a r and om population sample ( n = 10,400 ) . RESULTS A diagnosis of asthma was given to 96 of the 282 subjects . Subjects with asthma had higher FeNO levels than subjects with non-specific asthma symptoms in all three smoking strata ( p < 0.001 ) , with a percentual increase of FeNO by 76 % in never- , 71 % in ex- and 60 % in current smokers . The area under the ROC-curve was similar in never- , ex- and current smokers ( 0.72 vs. 0.74 vs. 0.70 ) . The cut-offs were approximately 30 % lower for either 90 % specificity ( 22 vs. 31 ppb ) or 90 % sensitivity ( 7 vs. 10 ppb ) in current vs. never-smokers . CONCLUSIONS FeNO could differentiate asthmatic subjects from non-asthmatic subjects with asthma-like symptoms equally well in both never- and current smokers within a r and om population sample . The FeNO cut-off levels needed in order to achieve high sensitivity or specificity were lower in current smokers BACKGROUND Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care re sources . Preventing exacerbations remains an important goal of therapy . There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations . METHODS We conducted a r and omized , double-blind , placebo-controlled , parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations . Subjects received infusions of either mepolizumab , an anti-interleukin-5 monoclonal antibody ( 29 subjects ) , or placebo ( 32 ) at monthly intervals for 1 year . The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase . Secondary outcomes included a change in asthma symptoms , scores on the Asthma Quality of Life Question naire ( AQLQ , in which scores range from 1 to 7 , with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinical ly important ) , forced expiratory volume in 1 second ( FEV(1 ) ) after use of a bronchodilator , airway hyperresponsiveness , and eosinophil counts in the blood and sputum . RESULTS Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks ( 2.0 vs. 3.4 mean exacerbations per subject ; relative risk , 0.57 ; 95 % confidence interval [ CI ] , 0.32 to 0.92 ; P=0.02 ) and with a significant improvement in the score on the AQLQ ( mean increase from baseline , 0.55 vs. 0.19 ; mean difference between groups , 0.35 ; 95 % CI , 0.08 to 0.62 ; P=0.02 ) . Mepolizumab significantly lowered eosinophil counts in the blood ( P<0.001 ) and sputum ( P=0.002 ) . There were no significant differences between the groups with respect to symptoms , FEV(1 ) after bronchodilator use , or airway hyperresponsiveness . The only serious adverse events reported were hospitalizations for acute severe asthma . CONCLUSIONS Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma . The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population . ( Current Controlled Trials number , IS RCT N75169762 . |
11,186 | 30,462,676 | Finally , two annual applications of silver diamine fluoride showed the best nonrestorative approach to arrest caries lesions on occlusal and smooth surfaces .
However , few of the included studies provided evidence to strongly recommend the best treatment option . | BACKGROUND A systematic quantitative evaluation of the available evidence of the treatment for caries lesions in primary teeth that considers how different caries progressions lead to the need for distinct interventions might provide additional useful information for clinical evidence -based decision making .
The aim of this systematic review and network meta- analysis was to verify the effect of the treatments on caries lesion arrestment ( CLA ) or the success rate ( SR ) of dentin caries lesion treatments in the primary teeth .
DISCUSSION / CONCLUSIONS The treatments for dentin caries lesions in primary teeth depend on the depth of progression and the surface involved . | OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome Objectives This study aim ed to test the hypothesis that there is no difference in the survival rates of molars treated according to the conventional restorative treatment ( CRT ) using amalgam , atraumatic restorative treatment ( ART ) using high-viscosity glass ionomer , and ultraconservative treatment ( UCT ) protocol after 3.5 years . Material s and methods Cavitated primary molars were treated according to CRT , ART , and UCT ( small cavities were restored with ART and medium/large cavities were daily cleaned with toothpaste/toothbrush under supervision ) . Molar extraction s result ing from toothache , sepsis , or pulp exposure were failures . The Kaplan – Meier method was used to estimate the survival curves . Results The numbers of treated teeth , among the 302 6–7-year-old children , were 341 ( CRT ) , 244 ( ART ) , and 281 ( for UCT group : 109 small ART , 166 open cavities , and 6 combinations ) . Protocol groups were similar at baseline regarding gender and mean decayed missing filled tooth score , but not regarding age and type of surface . The numbers of molars extracted were 22 ( CRT ) , 16 ( ART ) , and 26 ( UCT ) . Fistulae were most often recorded . After 3.5 years , the cumulative survival rate ± st and ard error for all molars treated was 90.9 ± 2.0 % with CRT , 90.4 ± 2.4 % with ART , and 88.6 ± 1.9 % with UCT ( p = 0.13 ) . Only a type of surface effect was observed over the 3.5-year period : survival rates for molars were higher for single- than for multiple-surface cavities . Conclusion There was no difference in the cumulative survival rates of primary molars treated according to the CRT , ART , and UCT protocol s over a 3.5-year period . Clinical relevance Keeping cavities in primary molars biofilm-free might be another treatment option alongside restoring such cavities through conventional and ART protocol OBJECTIVE To compare the survival of glass ionomer cement ( GIC ) restorations placed in a dental clinic setting using both the atraumatic restorative treatment ( ART ) approach with h and instruments , and conventional cavity preparation with rotary instruments . METHOD AND MATERIAL S Two encapsulated high-strength conventional GICs ( Fuji IX GP , Ketac-Molar Aplicap ) were placed in 82 Class I and 53 Class II preparations and one encapsulated non-gamma 2 amalgam alloy ( GK-amalgam ) was placed in 32 Class I preparations , in the primary molars of 60 Chinese children with a mean age of 7.40 + /- 1.24 ( SD ) years . Thus , 9 treatment groups were formed . RESULTS After two years , there were no significant survival differences found among 7 of the 9 treatment groups ( p = 0.99 ) . However , two groups comprising Fuji IX GP and Ketac-Molar Aplicap placed in Class II cavities prepared using the ART approach showed significantly lower restoration survivals ( p < 0.001 ) . Only 3 of the 72 initially sealed fissures adjacent to the restorations appeared to retain any GIC material . CONCLUSIONS In a clinic setting , both the ART h and instrument and conventional rotary instrument methods were equally suitable for high Class I restoration survival , but not for Class II restoration survival where the conventional cavity preparation method was preferable Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background The resin-based pit and fissure sealant is considered a successful tool in caries prevention , however there is a growing evidence of its use in controlling already established caries in posterior teeth . The aim of this clinical trial is to verify the efficacy of pit and fissure sealants in arresting dentinal caries lesions compared to partial excavation and restorative treatment in primary molar teeth . Methods Thirty six patients with occlusal cavitated primary molar reaching outer half of dentin were selected . The patients were r and omly allocated into two groups : sealant application ( experimental group – n = 17 ) and restoration with composite resin ( control group – n = 19 ) . Clinical and radiograph evaluation were performed after 6 , 12 and 18 months . The chi-square test was used to verify the distribution of characteristics variables of the sample among the groups . The survival rate of treatments was evaluated using Kaplan – Meier survival and log-rank test . Fisher ’s Exact and logistic regression tests were calculated in each evaluation period ( α = 5 % ) . Results The control group showed significantly better clinical survival after 18 months ( p = 0.0025 ) . In both groups , no caries progression was registered on the radiographic evaluations . Conclusions Sealing had similar efficacy in the arrestment of caries progression of cavitated occlusal lesions compared to partial excavation of the lesions , even though the frequency of re-treatments was significantly higher in sealed lesions . Trial registration Registro Brasileiro de Ensaios Clínicos ( ReBEC ) : Atraumatic restorative treatment ( ART ) and minimal intervention treatment ( MIT ) techniques were evaluated under field conditions in 5 regions of the Western Cape Province of South Africa , where caries prevalence exceeds 60 % and remains mostly untreated . The purpose of the study was to compare and evaluate results of ART and MIT techniques in the primary dentition of 6 - 9 year-old schoolchildren using glass-ionomer ( GI ) ( Fuji IX ) and compomer ( Dyract AP ) material s. At baseline 401 children were treated , and 1,119 restorations placed by 5 calibrated dentists , 53 % with ART ( using h and instruments only ) and 47 % with MIT ( minimal use of slow h and -piece ) techniques . Evaluations were done with a CPI periodontal probe to measure marginal defects and to detect decay . A pain assessment for the restoration procedures indicated that 80 % of subjects experienced no pain , 18 % discomfort and slight pain , and 2 % required local anaesthetic . After one year 90.5 % of subjects and 80 % of restorations were followed up ( 11.1 % lost as a result of exfoliation ) ; of these restorations 86 % were clinical ly acceptable ( 84.1 % of the ART and 88 % of the MIT ) . With the art technique 82.7 % of GI restorations and 85.6 % , of compomer restorations were acceptable . With the MIT technique 86.5 % of GI restorations and 89.9 % of compomer restorations were acceptable . Success of restorations per region varied significantly : regions 1 and 2 - 90 % , region 3 - 80 % , region 4 - 70 % and region 5 - 95 % . There were no significant statistical differences in respect of material s or methods employed . ART and MIT techniques were well accepted as complementary caries approaches by operators . One-year results show that ART and MIT techniques were successful , substantiating its use for the primary dentition in areas with high caries prevalence . Longer-term assessment s are required Aims To prospect ively report on the survival of resin-modified glass ionomer cement ( RMGIC ) , photac-fil and pre-formed stainless steel crown ( SSC ) restorations in primary molar teeth placed over a seven-year period in a specialist paediatric dental practice under private contract of remuneration . Method All primary molar restorations placed by a specialist paediatric dentist over a seven-year period were review ed and the outcome results recorded . Data were recorded at review visits until June 30 , 2003 . Data recorded included Class I restorations , Class II restorations and SSC . The Class II cavities were either mesial or distal , with or without buccal/palatal extensions . If both proximal surfaces were decayed or if after cavity preparation the result ant outline form was significantly larger than the minimal classical form , RMGIC was not used ; an SSC was placed instead . Stainless steel crown preparation followed conventional guidelines . The crowns were cemented with reinforced zinc oxide and eugenol ( Kalzinol ) . The status was recorded as satisfactory restoration , tooth exfoliated , tooth extracted for orthodontic reasons with the date of extraction , or needing replacement . If replaced then the reason for replacement was also recorded . Results A total of 544 Class I RMGICs , 962 Class II RMGICs , and 1,010 SSCs were placed . At the last review of each restoration , 98.3 % of Class I , 97.3 % of Class II RMGICs and 97.0 % of SSCs were either satisfactory or withdrawn intact . Conclusion Under the conditions of private specialist practice -based study SSCs continued to prove very successful for the restoration of larger cavities and for pulp-treated primary molar teeth . For the smaller cavities RMGIC were also very successful The aim of this study was to assess the possibility to arrest occlusal caries lesions in adults by sealant as well as to assess the presence of radiographic progression , arrest , and regression of the sealed lesions . Seventy-two occlusal caries lesions in 52 adult patients referred to restorative treatment by senior lecturers at School of Dentistry , Copenhagen , Denmark were included . In case the patient had more than one occlusal caries lesion , r and omization between sealing and restoration was made ; otherwise , the lesion was sealed . In total , 60 resin sealants and 12 composite restorations were made . Follow-up period was 25–38 months ( mean = 33 months ) . Data were analyzed using non-parametric statistics including kappa statistics . After 2–3 years , the dropout rate was 15 % ; two patients did not show up for control and nine previously sealed lesions were restored by the patients ' general practitioners . All 12 restorations and 39 of the remaining 49 sealants were well functioning , seven ( 14 % ) sealants were repaired/replaced due to failure , and three ( 6 % ) sealed lesions were restored due to caries progression ( p > 0.05 ) . The radiographic assessment showed caries progression beneath five ( 10 % ) sealants , caries regression beneath one ( 2 % ) sealant , and unchanged depth beneath 43 ( 88 % ) sealants and all restorations ( p > 0.05 ) . The majority of the referred lesions were successfully arrested by sealants , indicating the possibility for extending the criteria for sealing occlusal caries lesions in adults . However , a longer observation period is needed for final conclusion . Extending the criteria of therapeutic sealing of occlusal caries lesions in adults will lead to increased dental health BACKGROUND Silver diamine fluoride ( SDF ) is an effective agent for the arrest of caries in children , is easy to apply and can be used outside the clinical environment . Interim restorative treatment ( IRT ) using glass ionomer cement has also been cl aim ed to be a simple and effective method to arrest caries in deciduous teeth . OBJECTIVE To examine whether , for underprivileged schoolchildren with cavities , treatment with 30 % SDF gives better results than IRT for carries arrest . METHOD This r and omised controlled study compares the effect of IRT ( FUJI IX ) with 30 % SDF in 91 children aged 5 - 6 years . RESULTS After 1 year , treatment with SDF was more effective [ relative risk ( RR ) = 66.9 % ] than IRT ( RR = 38.6 % ) for the arrest of caries ; this was statistically significant ( P < 0.05 ) . CONCLUSION The SDF technique showed better results than IRT for the arrest of cavities in deciduous teeth , indicating that its use for underprivileged communities may justify a paradigm shift in paediatric dentistry This study compared the survival of restorations produced through the atraumatic restorative treatment ( ART ) approach using glass-ionomer with those produced through the traditional approach using amalgam ( MTA ) in deciduous dentitions over a period of 3 years . Using a parallel group design , 835 grade 1 children , aged 6–7 years , participated . A total of 482 children were treated through the ART and 353 children through the MTA approach . Eight dentists produced a total of 1,891 single- and multiple-surface restorations . After 3 years , 22.1 % of the restorations were lost for evaluation . There was a statistically significant difference in the combined survival of all single- and multiple-surface restorations between the two approaches in favour of the ART approach ( p = 0.04 ) . The study revealed a 3-year cumulative survival percentage of single-surface ART and MTA restorations of 86.1 and 79.6 % , respectively . The difference was statistically significant ( p = 0.03 ) . The main reasons for both single-surface ART and MTA restorations to fail was ‘ restoration missing ’ followed by ‘ gross marginal defect ’ . The 3-year cumulative survival percentages of multiple-surface ART and MTA restorations were 48.7 and 42.9 % , respectively . The difference was not statistically significant ( p > 0.05 ) . The 3-year survival percentages of single- and multiple- surface ART and MTA restorations varied widely amongst the 8 operators with an operator effect ( p = 0.001 ) for multiple-surface MTA restorations . It can be concluded that the ART approach using glass-ionomer yielded better results in treating dentinal lesions in deciduous teeth than did the traditional approach using amalgam after 3 years . It is recommended to select the ART approach to complement the other activities of the school oral health programme BACKGROUND The authors evaluated the 24-month performance of a packable resin-based composite/dentin bonding system and a high-viscosity glass ionomer cement ( GIC ) in restorations placed in primary molars with the atraumatic restorative treatment ( ART ) approach . METHODS Three dentists placed 419 restorations in 219 children aged 6 through 10 years who had bilateral matched pairs of carious posterior Class I and II primary teeth . They used a split-mouth design to place the two material s , which were assigned r and omly to contralateral sides . The authors evaluated the restorations according to U.S. Public Health Service Ryge criteria . RESULTS After 24 months , 96.7 percent of the Class I GIC restorations and 91 percent of the resin-based composite restorations survived , while the success rates for the Class II restorations were 76.1 percent and 82 percent for the GIC and resin-based composite restorations , respectively . The survival rate of the Class II resin-based composite restorations was 5.9 percent higher than that of the GIC restorations at the 24-month evaluation , but this difference was not statistically significant . However , the study results showed a statistically significant difference in survival rates between Class I and II restorations for both material s. CONCLUSION AND CLINICAL IMPLICATION S The two-year clinical performance of both material s was satisfactory for the restoration of Class I and II primary molars using the ART approach OBJECTIVES The aims of this study are to assess the feasibility of the Atraumatic Restorative Treatment ( ART ) approach in primary teeth and to compare the ART approach with traditional amalgam restorations in primary molars . METHODS This study was conducted in a paediatric dentistry clinic in Kuwait between April 1999 and December 2001 . The ART and amalgam restorations were placed r and omly on comparable pairs of primary molars , if available . In addition , the ART approach was used for other primary teeth that had no pulpal involvement and no perceived pain before treatment . The restorations were assessed by both the ART evaluation criteria and USPHS criteria in August-September 2000 and in August-December 2001 . The mean follow-up period for the restorations was 8.3 months in the first assessment ( 2000 ) and 22 months in the second assessment ( 2001 ) . The assessment was possible for 35 children ( mean age = 5.7 years ) , 18 of whom had comparable pairs ( n = 35 pairs ) of restorations in their primary molars . In addition , 48 other ART restorations were assessed in 2000 and 42 in 2001 . RESULTS In a 2-year follow-up , 89.6 % of all ART restorations were considered successful . The failure rate of the comparable pairs of ART and amalgam restorations was 5.7 % . There was no significant difference in success rate between ART and amalgam techniques . CONCLUSIONS Based on a 2-year follow-up evaluation , the class I ART restorations seemed to have a high success rate , indicating the appropriateness of the ART approach in primary teeth OBJECTIVES This study aim ed to compare the effectiveness of three topical fluoride application protocol s in arresting dentine caries in primary teeth of preschool children in a fluori date d area . METHODS Children aged 3 - 4 years who had at least one active dentine caries lesion were r and omly allocated into three intervention groups : Group 1-application of 30 % silver diammine fluoride ( SDF ) solution every 12 months ; Group 2-three applications of 30 % SDF solution at weekly interval at baseline ; and Group 3-three applications of 5 % sodium fluoride ( NaF ) varnish at weekly interval at baseline . A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested . RESULTS A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline . After 18 months , 275 children ( 91 % ) remained in the study . The caries arrest rates at tooth surface level were 40 % , 35 % and 27 % for Groups 1 , 2 and 3 , respectively ( p<0.001 ) . Result of the multi-level survival analysis showed that the two SDF application protocol s could shorten the time to arrest of dentine caries compared with the NaF application protocol . Presence of plaque on lesion surface , tooth type and tooth surface all had significant effects on caries arrest rates . CONCLUSIONS Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish . CLINICAL SIGNIFICANCE In a water fluori date d area , application of SDF solution , either three weekly applications at baseline or annually , can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline Minimal invasive approaches to managing caries , such as partial caries removal techniques , are showing increasing evidence of improved outcomes over the conventional complete caries removal . There is also increasing interest in techniques where no caries is removed . We present the 1-yr results of clinical efficacy for 3 caries management options for occlusoproximal cavitated lesions in primary molars : conventional restorations ( CR ; complete caries removal and compomer restoration ) , Hall technique ( HT ; no caries removal , sealing in with stainless steel crowns ) , and nonrestorative caries treatment ( N RCT ; no caries removal , opening up the cavity , teaching brushing and fluoride application ) . In sum , 169 children ( 3 - 8 yr old ; mean , 5.56 ± 1.45 yr ) were enrolled in this secondary care – based , 3-arm , parallel-group , r and omized clinical trial . Treatments were carried out by specialist pediatric dentists or postgraduate trainees . One lesion per child received CR , HT , or N RCT . Outcome measures were clinical failure rates , grouped as minor failure ( restoration loss/need for replacement , reversible pulpitis , caries progression , etc . ) and major failure ( irreversible pulpitis , abscess , etc . ) . There were 148 children ( 87.6 % ) with a minimum follow-up of 11 mo ( mean , 12.23 ± 0.98 mo ) . Twenty teeth were recorded as having at least 1 minor failure : N RCT , n = 8 ( 5 % ) ; CR , n = 11 ( 7 % ) ; HT , n = 1 ( 1 % ) ( p = .002 , 95 % CI = 0.001 to 0.003 ) . Only the comparison between N RCT and CR showed no significant difference ( p = .79 , 95 % CI = 0.78 to 0.80 ) . Nine ( 6 % ) experienced at least 1 major failure : N RCT , n = 4 ( 2 % ) ; CR , n = 5 ( 3 % ) ; HT , n = 0 ( 0 % ) ( p = .002 , 95 % CI = 0.001 to 0.003 ) . Individual comparison of N RCT and CR showed no statistically significant difference in major failures ( p = .75 , 95 % CI = 0.73 to 0.76 ) . Success and failure rates were not significantly affected by pediatric dentists ’ level of experience ( p = .13 , 95 % CI = 0.12 to 0.14 ) . The HT was significantly more successful clinical ly than N RCT and CR after 1 yr , while pairwise analyses showed comparable results for treatment success between N RCT and CR ( Clinical Trials.gov NCT01797458 ) BACKGROUND . Despite the efficacy of non-drilling approaches to manage non-cavitated dentin occlusal lesions ( NCDOL ) in permanent teeth , there is no data validating this type of therapy in the primary dentition . AIM . To compare the efficacy of a traditional fissure sealant in managing NCDOL in primary molars . DESIGN . This study is a r and omized controlled clinical trial with a split-mouth design . Thirty schoolchildren with two NCDOL were selected and divided into two groups . The experimental group received a resin-based fissure sealant , whereas the control group was treated with a conventional composite resin . Treatment efficacy was evaluated after 1 year by means of clinical and radiographic examinations . RESULTS . The two treatment modalities were found to be similarly effective in managing DONCL in primary molars . CONCLUSION . For the management of non-cavitated dentin occlusal caries in primary teeth , the invasive approach can be replaced with non-drilling fissure sealing techniques OBJECTIVES the purpose of this study was to determine the mineral loss on surrounding enamel restored with glass ionomer cements ( GIC ) after erosive and cariogenic challenges . METHODS Bovine enamel specimens were r and omly assigned into six groups according to the restorative material : G1 - composite resin ; G2 - high viscous GIC ; G3 - resin-modified glass ionomer with nanoparticles ; G4 - encapsulated resin-modified GIC ; G5 - encapsulated high viscous GIC ; G6 - resin-modified GIC . After restorative procedures , half of specimens in each group were su bmi tted to caries challenge using a pH cycling model for 5 days , and the other half were su bmi tted to erosive challenge in citric acid for 10 min . Before and after the challenges , surface Knoop microhardness assessment s were performed and mineral changes were calculated for adjacent enamel at different distances from restorative margin . RESULTS Data were compared for significant differences using two-way ANOVA and Student-Newman-Keuls tests ( p<0.05 ) . Erosive challenge significantly reduced enamel surface hardness , but no significant difference was observed irrespectively restorative material s ( p>0.05 ) . The cariogenic challenge promoted a higher surface hardness loss for the resin-modified GIC ( G4 ) and only for the High viscous GIC ( G2 ) an increase in surface hardness was observed . For enamel analyses , significant differences were observed with respect to the different material s ( p<0.001 ) and distances ( p=0.023 ) . Specimens restored with the composite resin presented higher mineral loss and specimens restored with the conventional high viscous GIC and the encapsulated resin-modified GIC presented the lowest values for mineral loss . CONCLUSION The GICs exerts protective effect only for cariogenic challenge |
11,187 | 30,656,650 | Most trials were conducted in secondary care setting s. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin .
There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration .
We did not find any evidence that appetite loss , dizziness , headache , respiratory symptoms , blood infections , skin and soft tissue infections , itching , or rashes were reported more often by participants treated with macrolides compared to placebo .
Macrolides caused less cough ( OR 0.57 , 95 % CI 0.40 to 0.80 ; moderate- quality evidence ) and fewer respiratory tract infections ( OR 0.70 , 95 % CI 0.62 to 0.80 ; moderate- quality evidence ) compared to placebo , probably because these are not adverse events , but rather characteristics of the indications for the antibiotics .
Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic .
The macrolides as a group clearly increased rates of gastrointestinal adverse events .
This was especially true for the adverse event of bacterial resistance | BACKGROUND Macrolide antibiotics ( macrolides ) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections .
However , macrolides also expose people to the risk of adverse events .
The current underst and ing of adverse events is mostly derived from observational studies , which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated .
Because adverse events are treatment-specific , rather than disease-specific , it is possible to increase the number of adverse events available for analysis by combining r and omised controlled trials ( RCTs ) of the same treatment across different diseases .
OBJECTIVES To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication . | OBJECTIVE To compare the efficacy and safety of azithromycin with ofloxacin in patients with uncomplicated typhoid fever . MATERIAL AND METHODS Forty adult patients with bacteriologically or serologically diagnosed , uncomplicated typhoid fever were included from Medicine out-patient department at Government medical college , Amritsar , India . They were r and omized into 2 groups of 20 patients each . Group I : patients received ofloxacin 200 mg orally twice daily for 7 days . Group II : Patients received Azithromycin orally 1 gm on day 1 and then 500 mg daily from day 2 to day 6 . The following parameters were noted a ) fever clearance time b ) cure rate c ) adverse drug reaction d ) recurrence of symptoms , if any , during 4 weeks follow up . RESULTS Nineteen out of 20 patients from group I were cured with mean fever clearance time of 3.68 days while all 20 patients from group II were cured with mean fever clearance time of 3.65 days . No significant side effects were noted in any of the patients . No relapse was recorded in the present study in a follow up period of 4 weeks in both study groups . CONCLUSION Both ofloxacin and Azithromycin are almost equally efficacious and safe in treatment of typhoid fever with no major adverse effect . Azithromycin is an effective alternative in conditions where ofloxacin is contraindicated i.e. , children , pregnant women and quinolone resistant cases of typhoid fever Although long-term azithromycin decreases exacerbation frequency in bronchiectasis , increased macrolide resistance is concerning . We investigated macrolide resistance determinants in a secondary analysis of a multicenter r and omized controlled trial . Indigenous Australian children living in remote regions and urban New Zeal and Māori and Pacific Isl and er children with bronchiectasis were r and omized to weekly azithromycin ( 30 mg/kg ) or placebo for up to 24 months and followed post-intervention for up to 12 months . Nurses administered and recorded medications given and collected nasopharyngeal swabs 3–6 monthly for culture and antimicrobial susceptibility testing . Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups , while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher . Australian children , compared to New Zeal and children , had higher carriage overall , significantly higher carriage of macrolide-resistant bacteria at baseline ( 16/38 versus 2/40 children ) and during the intervention ( 69/152 versus 22/239 swabs ) , and lower mean adherence to study medication ( 63 % versus 92 % ) . Adherence ≥70 % ( versus < 70 % ) in the Australian azithromycin group was associated with lower carriage of any pathogen [ odds ratio ( OR ) 0.19 , 95 % confidence interval ( CI ) 0.07–0.53 ] and fewer macrolide-resistant pathogens ( OR 0.34 , 95 % CI 0.14–0.81 ) . Post-intervention ( median 6 months ) , macrolide resistance in S. pneumoniae declined significantly in the azithromycin group , from 79 % ( 11/14 ) to 7 % ( 1/14 ) of positive swabs , but S. aureus strains remained 100 % macrolide resistant . Azithromycin treatment , the Australian remote setting , and adherence < 70 % were significant independent determinants of macrolide resistance in children with bronchiectasis . Adherence to treatment may limit macrolide resistance by suppressing carriage Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections ( LRTI ) . Severe asthma is heterogeneous , encompassing eosinophilic and non-eosinophilic ( mainly neutrophilic ) phenotypes . Patients with neutropilic airway diseases may benefit from macrolides . Methods We performed a r and omised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma . Subjects received low-dose azithromycin ( n=55 ) or placebo ( n=54 ) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months . The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase . Secondary efficacy outcomes included lung function and scores on the Asthma Control Question naire ( ACQ ) and Asthma Quality of Life Question naire ( AQLQ ) . Results The rate of primary endpoints ( PEPs ) during 6 months was not significantly different between the two treatment groups : 0.75 PEPs ( 95 % CI 0.55 to 1.01 ) per subject in the azithromycin group versus 0.81 PEPs ( 95 % CI 0.61 to 1.09 ) in the placebo group ( p=0.682 ) . In a predefined subgroup analysis according to the inflammatory phenotype , azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma ( blood eosinophilia ≤200/µl ) : 0.44 PEPs ( 95 % CI 0.25 to 0.78 ) versus 1.03 PEPs ( 95 % CI 0.72 to 1.48 ) ( p=0.013 ) . Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function . Azithromycin was well tolerated , but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci . Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma . However , the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study . Clinical Trials.gov number NCT00760838 Treatment of osteitis after surgical removal of the third molar of the m and ible is still a clinical problem . A total of 140 patients undergoing operations for removal of an impacted third molar of the m and ible , were included in a double-blind study . Placebo or antibiotics - azidocillin , erythromycin , clindamycin and doxycycline - were given to the patients preoperatively and for the following 7 days . The concentrations in serum , alveolar serum and m and ibular bone were measured and the postoperative courses - pain , trismus , swelling and wound-healing - were recorded . No correlation was obtained between the antibiotic concentration and the postoperative complaints , except in the azidocillin group on day 2 , in which fewer complaints were noticed in patients with high concentrations of the drug at the time of operations . The 80 patients in the antibiotic groups responded significantly better with respect to wound-healing than the 60 patients in the placebo groups . Only 15 operations lasted more than 15 min and the three of them which subsequently result ed in alveolitis were in the placebo groups . Antibiotics significantly reduced pain on day 7 postoperatively . In general , no statistically significant differences in trismus and swelling could be demonstrated between the patient groups . However , there was a significant difference between the placebo and doxycycline groups with respect to swelling ( day 2 postoperative , P < 0.01 ; day 5 postoperative , P < 0.05 ) . Thus systemically administered antibiotics offered only slight advantages in routine operations of impacted third m and ibular molars , but could decrease the rate of infections after traumatic operations OBJECTIVE To determine the efficacy of clarithromycin in the treatment of Pityriasis Rosea ( PR ) . STUDY DESIGN Double blind r and omized controlled trial . PLACE AND DURATION OF STUDY Dermatology OPD , Military Hospital , Rawalpindi , from July 2008 to July 2009 . METHODOLOGY Patients aged above 10 years , diagnosed with PR , were r and omly assigned to two groups of 30 each to receive either clarithromycin or similar-looking placebo for one week . Neither the patient nor the treating physician knew to which group the patient belonged . Patients were assessed at 1 , 2 , 4 and 6 weeks after presentation and compared for complete , partial or no response . RESULTS Among the 60 patients , no significant difference was found between the two groups at 2 weeks after presentation ( p = 0.598 ) . In the placebo group , complete response was seen in 20 ( 66.7 % ) , partial response in 3 ( 10.0 % ) while no response was seen in 7 ( 23.3 % ) . In clarithromycin group , there was complete response in 23 ( 76.7 % ) , partial response in 3 ( 10.0 % ) and no response in 4 ( 13.3 % ) patients . CONCLUSION Clarithromycin is not effective in treatment of pityriasis rosea Serial quantitative nasal cultures were performed on 87 healthy nasal carriers of Staphylococcus aureus , who were r and omly assigned to 7 days of oral therapy with erythromycin , rosamicin ( an investigational macrolide antibiotic ) , or placebo . Staphylococcal carrier rates decreased during therapy with both antibiotics ; however , erythromycin was significantly more effective in lowering carrier rates than was rosamicin . The anti-staphylococcal effects of both antibiotics were similar when the mean numbers of S. aureus isolated from positive cultures during therapy were compared . Side effects to each regimen were minimal New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria . The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83 % . We conducted a double-blind , placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity . After radical cure therapy , 300 r and omized subjects received azithromycin ( 148 subjects , 750-mg loading dose followed by 250 mg/d ) , placebo ( 77 ) , or doxycycline ( 75 , 100 mg/d ) . The end point was slide-proven parasitemia . There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks . Using incidence rates , the protective efficacy of azithromycin relative to placebo was 71.6 % ( 95 % confidence interval [ CI ] , 50.3 - 83.8 ) against P. falciparum malaria and 98.9 % ( 95 % CI , 93.1 - 99.9 ) against P. vivax malaria . Corresponding figures for doxycycline were 96.3 % ( 95 % CI , 85.4 - 99.6 ) and 98 % ( 95 % CI , 88.0 - 99.9 ) , respectively . Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria Summary Because of the significant morbidity and mortality associated with opportunistic infections , prophylaxis has become routine practice in the management of immunocompromised patients such as those with AIDS . Clarithromycin , an antimicrobial agent with a broad spectrum of activity against most common respiratory pathogens as well as many protozoa , has proven to be effective for both treatment and prophylaxis of Mycobacterium avium-intracellulare complex ( MAC ) infection in AIDS patients . Results of a large multinational placebo-controlled study suggest that clarithromycin for MAC prophylaxis provides additional benefits . In this study , clarithromycin statistically significantly reduced the incidence of Pneumocystis carinii pneumonia ( 5.3 % of clarithromycin recipients vs 10.0 % of placebo recipients ; p=0.021 ) , community-acquired pneumonia ( 7.1 vs 13.0 % ; p=0.010 ) , Giardia lamblia infection ( 0.9 vs 2.9 % ; p=0.048 ) , and neoplastic diseases ( 1.8 vs 4.1 % ; p=0.010 ) in AIDS patients with CD4 + counts of ≤ 100 cells/μl Background We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome ( BOS ) post lung transplantation . Methods We compared azithromycin ( 250 mg alternate days , 12 weeks ) with placebo . Primary outcome was FEV1 change at 12 weeks . Results 48 patients were r and omised ; ( 25 azithromycin , 23 placebo ) . It was established , post r and omisation that two did not have BOS . 46 patients were analysed as intention to treat ( ITT ) with 33 ‘ Completers ’ . ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal . Outcome The ITT analysis ( n=46 , 177 observations ) estimated mean difference in FEV1 between treatments ( azithromycin minus placebo ) was 0.035 L , with a 95 % CI of −0.112 L to 0.182 L ( p=0.6 ) . Five withdrawals , who were identified at the end of the study as having been r and omised to placebo ( four with rapid loss in FEV1 , one withdrawn consent ) had received rescue open-label azithromycin , with improvement in subsequent FEV1 at 12 weeks . Study Completers showed an estimated mean difference in FEV1 between treatment groups ( azithromycin minus placebo ) of 0.278 L , with 95 % CI for the mean difference : 0.170 L to 0.386 L ( p=<0.001 ) . Nine of 23 ITT patients in the azithromycin group had ≥10 % gain in FEV1 from baseline . No patients in the placebo group had ≥10 % gain in FEV1 from baseline while on placebo ( p=0.002 ) . Seven serious adverse events , three azithromycin , four in the placebo group , were deemed unrelated to study medication . Conclusions Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo . This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS . Trial registration number EU-CTR , 2006 - 000485 - 36/GB Summary Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children , suggesting antibiotics as a potential treatment for such episodes . We aim ed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms , hypothesising that it reduces the duration of the symptomatic period . Methods In this r and omised , double-blind , placebo-controlled trial , we recruited children aged 1–3 years , who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort ; a birth cohort consisting of the general Danish population of Zeal and , including Copenhagen . Exclusion criteria were macrolide allergy , heart , liver , neurological , and kidney disease , and , before each treatment , one or more clinical signs of pneumonia ( respiratory frequency of ≥50 breaths per min ; fever of ≥39 ° C ; C-reactive protein concentration of ≥476·20 nmol/L [ ≥50 mg/L ] ) . Each episode of asthma-like symptoms lasting at least 3 days was r and omly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospect i ve Studies on Asthma research unit . Each episode was r and omly allocated independently of previous treatment from a computer-generated list of r and om numbers in blocks of ten ( generated at the Pharmacy of Glostrup ) . Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases . The primary outcome was duration of the respiratory episode after treatment , verified by prospect i ve daily diaries and analysed with Poisson regression . Analyses were per protocol ( excluding those without a primary outcome measure or who did not receive treatment ) . This trial is registered with Clinical Trials.gov , number NCT01233297 . Findings Between Nov 17 , 2010 , and Jan 28 , 2014 , we r and omly allocated 158 asthma-like episodes in 72 children ( 79 [ 50 % ] to azithromycin and 79 [ 50 % ] to placebo ) . The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo . Azithromycin caused a significant shortening of the episode of 63·3 % ( 95 % CI 56·0–69·3 ; p<0·0001 ) . The effect size increased with early initiation of treatment , showing a reduction in episode duration of 83 % if treatment was initiated before day 6 of the episode compared with 36 % if initiated on or after day 6 ( p<0·0001 ) . We noted no differences in clinical adverse events between the azithromycin ( 18 [ 23 % ] of 78 episodes included in final analysis ) and placebo ( 24 [ 30 % ] of 79 ) groups ( p=0·30 ) , but we did not investigate bacterial resistance patterns after treatment . Interpretation Azithromycin reduced the duration of episodes of asthma-like symptoms in young children , suggesting that this drug could have a role in acute management of exacerbations . Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation . Funding Lundbeck Foundation , Danish Ministry of Health , Danish Council for Strategic Research , Capital Region Research Foundation Background Chronic obstructive pulmonary disease ( COPD ) is characterised by progressive development of airflow limitation that is poorly reversible . Because of a poor underst and ing of COPD pathogenesis , treatment is mostly symptomatic and new therapeutic strategies are limited . There is a direct relationship between the severity of the disease and the intensity of the inflammatory response . Besides smoking , one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections . Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases . There is consistent evidence that macrolide therapy reduces infectious exacerbations , decreases the requirement for additional antibiotics and improves nutritional measures . Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations . The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown . Until now , studies investigating macrolide therapy in COPD are limited . The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment . Methods / design The study is set up as a prospect i ve r and omised double-blind placebo-controlled single-centre trial . A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included . Subjects will be r and omised to receive either azithromycin 500 mg three times a week or placebo . Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment . Discussion We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD . Additionally , our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD . We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms . Trial registration http://www . clinical trials.gov OBJECTIVE Since preventive therapies for bronchopulmonary dysplasia ( BPD ) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD . METHODS Infants less than 1,250 g birth weight were r and omized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth . The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks . Aspirates were collected during the study to assay for Ureaplasma . The primary endpoints were incidence of BPD or mortality . ( Clinical Trials Identifier : NCT00319956 . ) RESULTS A total of 220 infants were enrolled ( n=111 azithromycin , and 109 placebo ) . Mortality was 18 % for the azithromycin group versus 22 % for the placebo group ( P = 0.45 ) . Incidence of BPD was 76 % for the azithromycin group versus 84 % for the placebo group ( P=0.2 ) . The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group , but was not statistically significant . The incidence of BPD in the Ureaplasma subgroup was 73 % in the azithromycin group versus 94 % in the placebo group ( P=0.03 ) . Analysis of patients in the Ureaplasma subgroup only , using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 ( 0.001 - 0.618 , 95 % confidence interval ) . CONCLUSIONS Routine use of azithromycin therapy for the prevention of BPD can not be recommended . The early treatment of Ureaplasma colonized/infected patients might be beneficial , but a larger multi-centered trial is required to assess this more definitively BACKGROUND AND OBJECTIVE We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis . The objectives were to demonstrate that this treatment reduces sputum volume , improves quality of life and to assess the lengths of effects after cessation of therapy . METHODS Seventy-eight patients with bronchiectasis confirmed by high-resolution computed tomography were included in this study . Subjects received oral azithromycin or placebo in a r and omized manner for 12 weeks followed by placebo for another 12 weeks . Sputum volume , St George 's Respiratory Question naire ( SGRQ ) score and spirometry were recorded at baseline , 12 weeks and 24 weeks , respectively . End-point measurements were compared from baseline to the end of each study phase . RESULTS Sixty-eight subjects were included in the analysis . Mean 24-h sputum volume significantly decreased ( P < 0.01 ) during the active treatment phase and remained low during the control phase ( P < 0.01 ) . The mean SGRQ total score with azithromycin decreased ( i.e. improved health status ) from baseline by more than the 4 points at the end of 12 and 24 weeks . Lung functions remained stable during oral azithromycin therapy and the subsequent control phase . CONCLUSIONS Twelve weeks administration of azithromycin in bronchiectasis produces significant reductions in mean sputum volume , health status and stabilization of lung function values . Sputum volume reduction and the improvement of quality of life were sustained for 12 weeks after cessation of azithromycin . ( Clinical trials.gov number NCT02107274 ) BACKGROUND Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome ( AIDS ) . We studied the efficacy and safety of prophylactic treatment with clarithromycin , a macrolide antibiotic . METHODS We conducted a r and omized , placebo-controlled , double-blind study of clarithromycin in patients with AIDS in the United States and Europe . Entry criteria included blood cultures that were negative for M. avium complex , a Karnofsky performance score of 50 or higher , a CD4 cell count of 100 or less per cubic millimeter , and a life expectancy of at least six months . RESULTS After the first interim analysis , the study was stopped . M. avium complex infection developed in 19 of the 333 patients ( 6 percent ) assigned to clarithromycin and in 53 of the 334 ( 16 percent ) assigned to placebo ( adjusted hazard ratio , 0.31 ; 95 percent confidence interval , 0.18 to 0.53 ; P<0.001 ) . During the follow-up period of about 10 months , 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died ( hazard ratio , 0.75 ; P=0.026 ) . In the clarithromycin group , isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin . Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion ( 11 percent in the clarithromycin group vs. 2 percent in the placebo group , P<0.001 ) and rectal disorders ( 8 percent vs. 3 percent , P = 0.007 ) ; however , the frequency of more severe adverse events was similar in the two groups ( 7 percent and 6 percent , respectively ) . CONCLUSIONS In patients with advanced AIDS , the prophylactic administration of clarithromycin is well tolerated , prevents M. avium complex infection , and reduces mortality Purpose : To compare the clinical benefit of isotretinoin ( 0.05 % ) and erythromycin ( 2 % ) gels alone and in combination ( Isotrexin ™ ) in acne patients . Procedure : The study was a r and omised placebo-controlled trial in acne patients who should benefit from topical therapy . Results : All treatment groups except placebo produced a time-related reduction in lesion counts , with the combined therapy producing the largest mean decrease . Between-group comparisons showed several significant differences . Conclusion : Isotrexin was significantly better than placebo at all time points for inflamed and total lesions , and was better than isotretinoin at week 4 . Side-effects were minimal Objectives : The respiratory pathogen Chlamydia pneumoniae ( C. pneumoniae ) produces acute and chronic lung infections and is associated with asthma . Evidence for effectiveness of antichlamydial antibiotics in asthma is limited . The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice setting s where most asthma is encountered and managed . The secondary objectives were to investigate ( 1 ) whether azithromycin treatment would affect any asthma outcomes and ( 2 ) whether C. pneumoniae serology would be related to outcomes . This report presents the secondary results . Design : R and omized , placebo-controlled , blinded ( participants , physicians , study personnel , data analysts ) , allocation-concealed parallel group clinical trial . Setting : Community-based health-care setting s located in four states and one Canadian province . Participants : Adults with stable , persistent asthma . Interventions : Azithromycin ( six weekly doses ) or identical matching placebo , plus usual community care . Outcome Measures : Juniper Asthma Quality of Life Question naire ( Juniper AQLQ ) , symptom , and medication changes from baseline ( pretreatment ) to 3 mo posttreatment ( follow-up ) ; C. pneumoniae IgG and IgA antibodies at baseline and follow-up . Results : Juniper AQLQ improved by 0.25 ( 95 % confidence interval ; −0.3 , 0.8 ) units , overall asthma symptoms improved by 0.68 ( 0.1 , 1.3 ) units , and rescue inhaler use decreased by 0.59 ( −0.5 , 1.6 ) daily administrations in azithromycin-treated compared to placebo-treated participants . Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up ( p = 0.04 ) , but IgG was not ( p = 0.63 ) . Overall asthma symptom improvement attributable to azithromycin was 28 % in high IgA participants versus 12 % in low IgA participants ( p for interaction = 0.27 ) . Conclusions : Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms . Larger community-based trials of antichlamydial antibiotics for asthma are warranted BACKGROUND Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries , similarly to other oral vaccines . The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem . Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens , we aim ed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity . METHODS We did a double-blind , r and omised , placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district , India . Infants were eligible to participate if they were 6 - 11 months old , available for the study duration , and lacked serum neutralising antibodies to serotype-3 poliovirus . Infants were r and omly assigned ( 1:1 ) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days , followed by serotype-3 monovalent oral poliovirus vaccine on day 14 . The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per- protocol population ( ie , all those who received azithromycin or placebo , oral poliovirus vaccine , and provided a blood sample according to the study protocol ) . Safety outcomes were assessed in all infants enrolled in the study . The trial is registered with the Clinical Trials Registry India , number CTRI/2014/05/004588 . FINDINGS Between Aug 5 , 2014 , and March 21 , 2015 , 754 infants were r and omly assigned : 376 to receive azithromycin and 378 to placebo . Of these , 348 ( 93 % ) of 376 in the azithromycin group and 357 ( 94 % ) of 378 infants in the placebo group completed the study per protocol . In the azithromycin group , 175 ( 50 % ) seroconverted to serotype-3 poliovirus compared with 192 ( 54 % ) in the placebo group ( risk ratio 0·94 , 95 % CI 0·81 - 1·08 ; p=0·366 ) . Azithromycin reduced faecal biomarkers of environmental enteropathy ( calprotectin , myeloperoxidase , α1-antitrypsin ) and the prevalence of bacterial but not viral or eukaryotic pathogens . Viral pathogens were associated with lower seroconversion . Three serious adverse events were reported ( two in the azithromycin group and one in the placebo group ) , but none was considered related to the study interventions . INTERPRETATION Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria . Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines . FUNDING Bill & Melinda Gates Foundation BACKGROUND Respiratory syncytial virus ( RSV ) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma . Because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model , demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing . OBJECTIVES We sought to investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of postbronchiolitis recurrent wheezing . METHOD We performed a r and omized , double-masked , placebo-controlled proof-of-concept trial in 40 otherwise healthy infants hospitalized with RSV bronchiolitis who were treated with azithromycin or placebo for 14 days . IL-8 levels were measured in nasal lavage fluid and serum on r and omization , day 8 , and day 15 ( nasal lavage only ) . The occurrence of wheezing episodes was assessed monthly over the ensuing 50 weeks . RESULTS Compared with placebo , azithromycin treatment did not reduce serum IL-8 levels at day 8 ( P = .6 ) but result ed in a greater decrease in nasal lavage fluid IL-8 levels by day 15 ( P = .03 ) . Twenty-two percent of azithromycin-treated participants experienced at least 3 wheezing episodes compared with 50 % of participants in the placebo group ( P = .07 ) . Azithromycin treatment result ed in prolonged time to the third wheezing episode ( P = .048 ) and in fewer days with respiratory symptoms over the subsequent year in comparison with placebo ( 36.7 vs 70.1 days , P = .01 ) . CONCLUSION In this proof-of-concept study azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels , prolonged the time to the third wheezing episode , and reduced overall respiratory morbidity over the subsequent year Background : Antibodies against Chlamydia pneumoniae are associated with an increased rate of expansion of small abdominal aortic aneurysms ( AAAs ) . Short-term follow-up trials have shown a transient reduction AAA growth rate , in macrolide treated compared with placebo . Therefore we analysed the influence of intermittent , long-term roxithromycin treatment on AAA expansion and referral for surgery . Methods : Eighty-four patients with small AAAs were r and omized to either an annual 4 weeks ’ treatment with roxithromycin or placebo , and followed prospect ively . Results : Intermittent , long-term Roxithromycin-treatment reduced mean annual growth rate by 36 % compared with placebo after adjustment for potential confounders . Long-term roxithromycin-treated patients had a 29 % lower risk of being referred for surgical evaluation , increasing to 57 % after adjusting for potential confounders . Conclusion : Annual 4 week treatment with 300 mg roxithromycin daily may reduce the progression of small AAAs , and later need for surgical repair . However , more robust studies are needed for confirmation BACKGROUND Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity . OBJECTIVE To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing . METHODS Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind , r and omized trial of clarithromycin vs placebo . Concentrations of tumor necrosis factor alpha ( TNF-alpha ) , interferon-gamma ( IFN-gamma ) , interleukin-1beta ( IL-1beta ) , IL-2 , IL-4 , IL-5 , IL-6 , IL-8 , IL-10 , granulocyte-macrophage colony-stimulating factor , RANTES , eotaxin , macrophage inflammatory protein 1alpha , macrophage inflammatory protein 1beta , and monocyte chemoattractant protein 1 were measured in serum and /or nasopharyngeal aspirates before , during , and after therapy . Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing . RESULTS Nasopharyngeal concentrations of TNF-alpha , IL-1beta , and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo . There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection . No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo . CONCLUSION Clarithromycin therapy reduces mucosal TNF-alpha , IL-1beta , and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing Background Neonatal deaths , estimated at approximately 4 million annually , now account for almost 40 % of global mortality in children aged under-five . Bacterial sepsis is a leading cause of neonatal mortality . Assuming the mother is the main source for bacterial transmission to newborns , the primary objective of the trial is to determine the impact of one oral dose of azithromycin , given to women in labour , on the newborn ’s bacterial carriage in the nasopharynx . Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life . Methods / design This is a Phase III , double -blind , placebo controlled r and omized clinical trial in which 830 women in labour were r and omized to either a single dose of 2 g oral azithromycin or placebo ( ratio 1:1 ) . The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia . A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8–10 days after delivery . Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery . Vaginal swabs and breast milk sample s were collected from the mothers , and the pathogens Streptococcus pneumoniae , Group B Streptococcus ( GBS ) and Staphylococcus aureus were isolated from the study sample s. For bacterial isolates , susceptibility pattern to azithromycin was determined using disk diffusion and E-test . Eye swabs were collected from newborns with eye discharge during the follow up period , and Chlamydial infection was assessed using molecular methods . Discussion This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn . If the trial confirms this hypothesis , the next step will be to assess the impact of this intervention on neonatal sepsis . The proposed intervention should be easily implementable in developing countries . Trial registration Clinical Trials.gov Identifier -NCT01800942- First received : February 26 , 2013 Background Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria . The optimum antibiotic choice remains unknown . We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo . Methods This was a single-centre , single-blind , r and omised placebo-controlled trial . Patients aged ≥45 years with COPD , FEV1<80 % predicted and chronic productive cough were r and omised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks , doxycycline 100 mg/day , azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks . The primary outcome was the change in total cultured bacterial load in sputum from baseline ; secondary outcomes included bacterial load by 16S quantitative PCR ( qPCR ) , sputum inflammation and antibiotic resistance . Results 99 patients were r and omised ; 86 completed follow-up , were able to expectorate sputum and were analysed . After adjustment , there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL ( 95 % CI −0.08 to 0.91 , p=0.10 ) with moxifloxacin , 0.11 ( −0.33 to 0.55 , p=0.62 ) with doxycycline and 0.08 ( −0.38 to 0.54 , p=0.73 ) with azithromycin from placebo , respectively . There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation . More treatment-related adverse events occurred with moxifloxacin . Of note , mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms . Conclusions Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy . Large increases in antibiotic resistance were seen in all treatment groups and this has important implication s for future studies . Trial registration number clinical trials.gov ( NCT01398072 ) BACKGROUND Chlamydia pneumoniae commonly causes respiratory infection , is vasotropic , causes atherosclerosis in animal models , and has been found in human atheromas . Whether it plays a causal role in clinical coronary artery disease ( CAD ) and is amenable to antibiotic therapy is uncertain . METHODS AND RESULTS CAD patients ( n=302 ) who had a seropositive reaction to C pneumoniae ( IgG titers > /=1:16 ) were r and omized to receive placebo or azithromycin , 500 mg/d for 3 days , then 500 mg/wk for 3 months . Circulating markers of inflammation ( C-reactive protein [ CRP ] , interleukin [IL]-1 , IL-6 , and tumor necrosis factor [TNF]-alpha ) , C pneumoniae antibody titers , and cardiovascular events were assessed at 3 and 6 months . Treatment groups were balanced , with age averaging 64 ( SD=10 ) years ; 89 % of the patients were male . Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 ( but not 3 ) months ( P=0 . 011 ) as well as the mean global rank sum change score : 531 ( SD=201 ) for active drug and 587 ( SD=190 ) for placebo ( P=0.027 ) . Specifically , change-score ranks were significantly lower for CRP ( P=0.011 ) and IL-6 ( P=0.043 ) . Antibody titers were unchanged , and number of clinical cardiovascular events at 6 months did not differ by therapy ( 9 for active drug , 7 for placebo ) . Azithromycin decreased infections requiring antibiotics ( 1 versus 12 at 3 months , P=0.002 ) but caused more mild , primarily gastrointestinal , adverse effects ( 36 versus 17 , P=0.003 ) . CONCLUSIONS In CAD patients positive for C pneumoniae antibodies , global tests of 4 markers of inflammation improved at 6 months with azithromycin . However , unlike another smaller study , no differences in antibody titers and clinical events were observed . Longer-term and larger studies of antichlamydial therapy are indicated Introduction Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response . Macrolides have anti-inflammatory properties , including the ability to downregulate the inflammatory cascade , attenuate excessive cytokine production in viral infections , and may reduce virus-related exacerbations . In this study , we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade . Methods and analysis A r and omised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3–6 months during two respiratory syncytial virus ( RSV ) seasons ( 2015–2016 and 2016–2017 ) . We expect a reduction of at least 20 % in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group . St and ard frequentist and Bayesian analyses will be performed using an intent-to-treat approach . Discussion We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidence d by a reduction in the total number of days with unscheduled face-to-face provider encounters . Ethics and dissemination This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014 . On completion , the results will be published . Trial registration number NCT02544984 RATIONALE Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) , but long-term side effects are unknown . OBJECTIVES To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin , 250 mg daily , added to usual care . METHODS Enrollment criteria included irreversible airflow limitation and AE COPD requiring corticosteroids , emergency department visit , or hospitalization in the prior year or use of supplemental oxygen . Recurrent events and cumulative incidence analyses compared treatment received for AE COPD by r and omization group , stratified by subgroups of interest . Cox proportional hazards models estimated treatment effects in subgroups adjusted for age , sex , smoking status , FEV1 % predicted , concomitant COPD medications , and oxygen use . MEASUREMENTS AND MAIN RESULTS Azithromycin was most effective in reducing AE COPD requiring both antibiotic and steroid treatment ( n = 1,113 ; cumulative incidence analysis , P = 0.0002 ; recurrent events analysis , P = 0.002 ) . No difference in treatment response by sex ( P = 0.75 ) , presence of chronic bronchitis ( P = 0.19 ) , concomitant inhaled therapy ( P = 0.29 ) , or supplemental oxygen use ( P = 0.23 ) was observed . Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response ( P = 0.02 and 0.04 , respectively ) . A significant interaction between treatment and current smoking was seen ( P = 0.03 ) and azithromycin did not reduce exacerbations in current smokers ( hazard ratio , 0.99 ; 95 % confidence interval , 0.71 - 1.38 ; P = 0.95 ) . CONCLUSIONS Azithromycin is most effective in preventing AE COPD requiring both antibiotic and steroid treatment . Adjusting for confounders , we saw no difference in efficacy by sex , history of chronic bronchitis , oxygen use , or concomitant COPD therapy . Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages . We found little evidence of treatment effect among current smokers . Clinical trial registered with www . clinical trials.gov ( NCT0011986 and NCT00325897 ) IMPORTANCE Macrolide antibiotics have been shown beneficial in cystic fibrosis ( CF ) and diffuse panbronchiolitis , and earlier findings also suggest a benefit in non-CF bronchiectasis . OBJECTIVE To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis . DESIGN , SETTING , AND PARTICIPANTS The BAT ( Bronchiectasis and Long-term Azithromycin Treatment ) study , a r and omized , double-blind , placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherl and s among 83 out patients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year . INTERVENTIONS Azithromycin ( 250 mg daily ) or placebo for 12 months . MAIN OUTCOME MEASURES Number of infectious exacerbations during 12 months of treatment . Secondary end points included lung function , sputum bacteriology , inflammatory markers , adverse effects , symptom scores , and quality of life . RESULTS Forty-three participants ( 52 % ) received azithromycin and 40 ( 48 % ) received placebo and were included in the modified intention-to-treat analysis . At end of study , the median number of exacerbations in the azithromycin group was 0 ( interquartile range [ IQR ] , 0 - 1 ) , compared with 2 ( IQR , 1 - 3 ) in the placebo group ( P < .001 ) . Thirty-two ( 80 % ) placebo-treated vs 20 ( 46 % ) azithromycin-treated individuals had at least 1 exacerbation ( hazard ratio , 0.29 [ 95 % CI , 0.16 - 0.51 ] ) . In a mixed-model analysis , change in forced expiratory volume in the first second of expiration ( percent of predicted ) over time differed between groups ( F1,78.8 = 4.085 , P = .047 ) , with an increase of 1.03 % per 3 months in the azithromycin group and a decrease of 0.10 % per 3 months in the placebo group . Gastrointestinal adverse effects occurred in 40 % of patients in the azithromycin group and in 5 % in the placebo group ( relative risk , 7.44 [ 95 % CI , 0.97 - 56.88 ] for abdominal pain and 8.36 [ 95 % CI , 1.10 - 63.15 ] for diarrhea ) but without need for discontinuation of study treatment . A macrolide resistance rate of 88 % was noted in azithromycin-treated individuals , compared with 26 % in the placebo group . CONCLUSIONS AND RELEVANCE Among adults with non-CF bronchiectasis , the daily use of azithromycin for 12 months compared with placebo result ed in a lower rate of infectious exacerbations . This could result in better quality of life and might influence survival , although effects on antibiotic resistance need to be considered . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00415350 Background : Mannose-binding lectin is a collectin involved in host defense against infection . Whether mannose-binding lectin deficiency is associated with acute exacerbations of chronic obstructive pulmonary disease is debated . Methods : Participants in a study design ed to determine if azithromycin taken daily for one year decreased acute exacerbations had serum mannose-binding lectin concentrations measured at the time of enrollment . Results : Sample s were obtained from 1037 subjects ( 91 % ) in the trial . The prevalence of mannose-binding lectin deficiency ranged from 0.5 % to 52.2 % , depending on how deficiency was defined . No differences in the prevalence of deficiency were observed with respect to any demographic variable assessed , and no differences were observed in time to first exacerbation , rate of exacerbations , or percentage of subjects requiring hospitalization for exacerbations in those with deficiency versus those without , regardless of how deficiency was defined . Conclusion : In a large sample of subjects with chronic obstructive pulmonary disease selected for having an increased risk of experiencing an acute exacerbation of chronic obstructive pulmonary disease , only 1.9 % had mannose-binding lectin concentrations below the normal range and we found no association between mannose-binding lectin concentrations and time to first acute exacerbation or frequency of acute exacerbations during one year of prospect i ve follow-up BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is characterised by airway inflammation , poor health status and recurrent infective exacerbations . Macrolide antibiotics have been shown to improve symptoms and exacerbation rate in chronic lung disease , particularly cystic fibrosis ( CF ) and diffuse pan-bronchiolitis . The effect of long-term oral clarithromycin on health status , sputum bacterial numbers and exacerbation rate in subjects with clinical ly stable COPD is undetermined . METHODS Subjects with moderate-to-severe COPD were recruited into a prospect i ve , double-blind , r and omised-controlled trial of 3-months oral clarithromycin ( Klaricid XL ) or placebo once-daily . The effect of clarithromycin on health status ( St. George respiratory and Short Form-36 question naires ) , sputum quantitative bacterial numbers and exacerbation rate were investigated . RESULTS Sixty-seven subjects ( 46 males ) were recruited ; 31 and 36 subjects received clarithromycin and placebo , respectively . There were 7(10 % ) withdrawals . Compared to placebo , clarithromycin did not significantly improve health status , sputum bacterial numbers , or exacerbation rate . CONCLUSIONS Three months of oral clarithromycin given to subjects with stable COPD does not improve health status , sputum bacterial numbers or exacerbation rate . Treatment of COPD with clarithromycin during the clinical stable state yields no clinical advantages and therefore can not be recommended as means of eliminating sputum bacteria or preventing infective exacerbations ABSTRACT To investigate the effect of slow-release ( SR ) clarithromycin on colonization and the development of resistance in oropharyngeal and nasal flora , a double-blind , r and omized , placebo-controlled trial was performed with 8 weeks of follow-up . A total of 296 patients with documented coronary artery disease were r and omized in the preoperative outpatient clinic to receive a daily dose of SR clarithromycin ( 500 mg ) ( CL group ) or placebo tablets ( PB group ) until the day of surgery . Nose and throat swabs were taken before the start of therapy , directly after the end of therapy , and 8 weeks later . The presence of potential pathogenic bacteria was determined , and if they were isolated , MIC testing was performed . Quantitative culture on media with and without macrolides was performed for the indigenous oropharyngeal flora . In addition , analysis of the mechanism of resistance was performed with the macrolide-resistant indigenous flora . Basic patient characteristics were comparable in the two treatment groups . The average number of tablets taken was 15 ( st and ard deviation = 6.4 ) . From the throat swabs , Haemophilus parainfluenzae was isolated and carriage was not affected in either of the treatment groups . Nasal carriage of Staphylococcus aureus , however , was significantly reduced in the CL group ( from 35.3 to 4.3 % ) compared to the PB group ( from 32.4 to 30.3 % ) ( P < 0.0001 ; relative risk [ RR ] , 7.0 ; 95 % confidence interval [ CI ] , 3.1 to 16.0 ) . Resistance to clarithromycin was present significantly more frequently in H. parainfluenzae in the CL group after treatment ( P = 0.007 ; RR , 1.6 ; 95 % CI , 1.1 to 2.3 ) ; also , the percentage of patients with resistance to macrolides in the indigenous flora after treatment was significantly higher in the CL group ( 31 to 69 % ) ( P < 0.0001 ; RR , 1.9 ; 95 % CI , 1.4 to 2.5 ) . This persisted for at least 8 weeks . This study shows that besides the effective elimination of nasal carriage of S. aureus , treatment with SR clarithromycin for approximately 2 weeks has a marked and sustained effect on the development of resistance in the oropharyngeal flora for at least 8 weeks INTRODUCTION Macrolide treatment has been reported to reduce the risk of recurrent ischaemic heart disease . The influence of a macrolide on the expansion rate of small abdominal aortic aneurysms ( AAA ) is unknown at present . The aim of this study was to investigate the effect of roxithromycin on the expansion rate of small AAA . MATERIAL S AND METHODS A total of 92 patients with a small AAA were recruited from two population s. One population consisted of 6.339 men aged 65 - 73 years who were offered participation in a mass screening programme for AAA at the local hospital . From this population 66 subjects were recruited . The remaining 26 were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 mm and 29 mm . The patients were r and omized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo , and followed for a mean of 1.5 years . RESULTS During the first year the mean annual expansion rate of AAA was reduced by 44 % in the macrolid group ( 1.56 mm/year ) compared to 2.80 mm/year after placebo ( p = 0.02 ) . During the second year the difference was only 5 % . Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking , diastolic blood pressure , and IgA level > or = 20 . The logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups , OR = 0.09 ( 95 % CI : 0.01 - 0.83 ) . DISCUSSION In comparison to placebo , roxithromycin 300 mg daily for four weeks reduced the expansion rate of AAA BACKGROUND There is serological evidence for an association between Chlamydia pneumoniae and coronary heart disease . We investigated the hypothesis that an antichlamydial macrolide antibiotic , roxithromycin , can prevent or reduce recurrent major ischaemic events in patients with unstable angina . METHODS The effect of roxithromycin was assessed in a double-blind , r and omised , prospect i ve , multicentre , parallel-group , placebo-controlled pilot study of 202 patients with unstable angina or non-Q-wave myocardial infa rct ion . Patients were r and omly assigned either roxithromycin 150 mg orally twice a day ( n = 102 ) or placebo orally twice a day ( n = 100 ) . The treatment was for 30 days . Patients were followed up for 6 months . We report the primary clinical endpoints ( cardiac ischaemic death , myocardial infa rct ion , and severe recurrent ischaemia ) , assessed at day 31 , in 202 patients on an intention-to-treat basis . FINDINGS A statistically significant reduction in the primary composite triple endpoint rates was observed in the roxithromycin group : p = 0.032 . The rate of severe recurrent ischaemia , myocardial infa rct ion , and ischaemic death was 5.4 % , 2.2 % , and 2.2 % in the placebo group and 1.1 % , 0 % , and 0 % , in the roxithromycin group , respectively . No major drug-related adverse effects were observed . INTERPRETATION Antichlamydial antibiotics may be useful in therapeutic intervention in addition to st and ard medication in patients with coronary-artery disease . Large-scale trials are needed to confirm these preliminary observations STUDY OBJECTIVES To determine the effect of clarithromycin therapy in patients with asthma . DESIGN R and omized , double blind , placebo-controlled trial . SETTING A tertiary referral center . PATIENTS OR PARTICIPANTS Fifty-five subjects with chronic , stable asthma recruited from the general Denver , CO , community . INTERVENTIONS Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction ( PCR ) and culture , followed by treatment with clarithromycin , 500 bid , or placebo for 6 weeks . MEASUREMENTS AND RESULTS Outcome variables were lung function , sinusitis as measured by CT , and the inflammatory mediators tumor necrosis factor (TNF)-alpha , interleukin (IL)-2 , IL-4 , IL-5 , and IL-12 messenger RNA ( mRNA ) measured via in situ hybridization , in airway biopsies , and BAL . Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics . Treatment result ed in a significant improvement in the FEV(1 ) , but only in the PCR-positive subjects ( 2.50 + /- 0.16 to 2.69 + /- 0.19 L , mean + /- SEM ; p = 0.05 ) . This was not appreciated in the PCR-negative subjects ( 2.59 + /- 0.24 to 2.54 + /- 0.18 L , p = 0.85 ) or the PCR-positive or PCR-negative subjects who received placebo . Sinus CTs revealed no change in sinusitis with clarithromycin treatment . In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects . However , the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha ( p = 0.006 ) , IL-5 ( p = 0.007 ) , and IL-12 ( p = 0.004 ) mRNA in BAL and TNF-alpha mRNA in airway tissue ( p = 0.0009 ) . The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha ( p = 0.01 ) and IL-12 ( p = 0.002 ) mRNA in BAL and TNF-alpha mRNA in airway tissue ( p = 0.004 ) . There were no significant differences in cytokine expression in those subjects who received placebo . CONCLUSIONS These observations support the hypothesis that clarithromycin therapy improves lung function , but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae This r and omized controlled trial examined the effects of preoperative oral erythromycin or nizatidine on gastric pH and volume . Sixty patients , ASA 1 and 2 status scheduled for elective surgery were studied . All subjects received oral study medication with 10 ml of water 60 minutes prior to surgery . Patients in Group 1 ( n=20 ) were given erythromycin 200 mg , in Group 2 ( n=20 ) nizatidine 300 mg , and in Group 3 ( n=20 ) placebo capsule . A nasogastric tube was inserted immediately after anaesthesia induction . Gastric content was aspirated , and volume and pH recorded . pH values determined in Group 1 were 5.6±1.87 ; in Group 2 , 5.65±1.92 and in Group 3 , 3.5±1.93 . There was no statistical difference between Groups 1 and 2 , but there was a statistically significant difference between Group 3 and Groups 1 and 2 ( P<0.001 ) . The volume of gastric content was 10.25±6.65 ml in Group 1 , 10.3±6.29 ml in Group 2 , and 20.25±16.72 ml in Group 3 . Again , there was no statistical difference between Groups 1 and 2 , but there was a statistically significant difference between Group 3 and Groups 1 and 2 ( P<0.05 ) . The proportion of patients considered “ at risk ” of significant lung injury should aspiration occur was 10 % of Group 1 , 5 % of Group 2 and 20 % of Group 3 ( not statistically different ) . We conclude that oral erythromycin and nizatidine given one hour prior to surgery are effective in reducing gastric pH and volume IMPORTANCE Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents . Erythromycin has strong gastric prokinetic properties . OBJECTIVE To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery . DESIGN , SETTING , AND PARTICIPANTS The Erythro-Emerge trial was a single-center , r and omized , double-blinded , placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals . We included 132 patients from March 25 , 2009 , through April 10 , 2013 , and all patients completed the study . R and omization was stratified for trauma and nontrauma procedures . The r and omization code was opened on April 23 , 2013 , and analyses were performed through July 26 , 2013 . We performed an intention-to-treat analysis . INTERVENTIONS Patients were r and omized to intravenous erythromycin lactobionate , 3 mg/kg , or placebo 15 minutes before tracheal intubation . Patients were followed up for 24 hours . MAIN OUTCOMES AND MEASURES The primary outcome was a clear stomach , defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation . The secondary outcome was the pH level of residual gastric content . RESULTS A clear stomach was diagnosed in 42 of 66 patients ( 64 % ) receiving placebo compared with 53 of 66 patients ( 80 % ) receiving erythromycin ( risk ratio , 1.26 [ 95 % CI , 1.01 - 1.57 ] ) . In the population undergoing surgery for nontrauma , the association between receipt of erythromycin and having a clear stomach ( adjusted odds ratio [ 95 % CI ] ) was statistically significant ( 13.4 [ 1.49 - 120 ] ; P = .02 ) ; in the population undergoing surgery for trauma , it was not ( 1.81 [ 0.64 - 5.16 ] ; P = .26 ) . Median ( interquartile range ) pH of the residual gastric liquid was 2 ( 1 - 4 ) in 36 patients receiving placebo and 6 ( 3 - 7 ) in 16 receiving erythromycin ( P = .002 ) . Patients receiving erythromycin had nausea ( 20 [ 30 % ] vs 4 [ 6 % ] ) and stomach cramps ( 15 [ 23 % ] vs 2 [ 3 % ] ) more often than those receiving placebo . One patient receiving erythromycin vomited before induction of anesthesia . CONCLUSIONS AND RELEVANCE In patients undergoing general anesthesia for emergency procedures , erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid . Erythromycin was particularly efficacious in the nontrauma population . Adverse effects were minor . Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00827216 Background Chlamydia pneumoniae is associated with coronary artery disease ( CAD ) , although its causal role is uncertain . A small preliminary study reported a > 50 % reduction in ischemic events by azithromycin , an antibiotic effective against C pneumoniae , in seropositive CAD patients . We tested this prospect ively in a larger , r and omized , double-blind study . Methods and Results CAD patients ( n=302 ) seropositive to C pneumoniae ( IgG titers ≥1:16 ) were r and omized to placebo or azithromycin 500 mg/d for 3 days and then 500 mg/wk for 3 months . The primary clinical end point included cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion ( MI ) , stroke , unstable angina , and unplanned coronary revascularization at 2 years . Treatment groups were balanced , and azithromycin was generally well tolerated . During the trial , 47 first primary events occurred ( cardiovascular death , 9 ; resuscitated cardiac arrest , 1 ; MI , 11 ; stroke , 3 ; unstable angina , 4 ; and unplanned coronary revascularization , 19 ) , with 22 events in the azithromycin group and 25 in the placebo group . There was no significant difference in the 1 primary end point between the 2 groups ( hazard ratio for azithromycin , 0.89 ; 95 % CI , 0.51 to 1.61;P = 0.74 ) . Events included 9 versus 7 occurring within 6 months and 13 versus 18 between 6 and 24 months in the azithromycin and placebo groups , respectively . Conclusions This study suggests that antibiotic therapy with azithromycin is not associated with marked early reductions ( ≥50 % ) in ischemic events as suggested by an initial published report . However , a clinical ly worthwhile benefit ( ie , 20 % to 30 % ) is still possible , although it may be delayed . Larger ( several thous and patient ) , longer-term ( ≥3 to 5 years ) antibiotic studies are therefore indicated Objective Bronchiolitis , one of the most common reasons for hospitalisation in young children , is particularly problematic in Indigenous children . Macrolides may be beneficial in setting s where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness . The aim of our double-blind placebo-controlled r and omised trial was to determine if a large single dose of azithromycin ( compared to placebo ) reduced length of stay ( LOS ) , duration of oxygen ( O2 ) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis . We also determined the effect of azithromycin on nasopharyngeal microbiology . Methods Children aged ≤18 months were r and omised to receive a single large dose ( 30 mg/kg ) of either azithromycin or placebo within 24 hrs of hospitalisation . Nasopharyngeal swabs were collected at baseline and 48hrs later . Primary endpoints ( LOS , O2 ) were monitored every 12 hrs . Hospitalised respiratory readmissions 6-months post discharge was collected . Results 97 children were r and omised ( n = 50 azithromycin , n = 47 placebo ) . Median LOS was similar in both groups ; azithromycin = 54 hours , placebo = 58 hours ( difference between groups of 4 hours 95%CI -8 , 13 , p = 0.6 ) . O2 requirement was not significantly different between groups ; Azithromycin = 35 hrs ; placebo = 42 hrs ( difference 7 hours , 95%CI -9 , 13 , p = 0.7 ) . Number of children re-hospitalised was similar 10 per group ( OR = 0.9 , 95%CI 0.3 , 2 , p = 0.8 ) . At least one virus was detected in 74 % of children . The azithromycin group had reduced nasopharyngeal bacterial carriage ( p = 0.01 ) but no difference in viral detection at 48 hours . Conclusion Although a single dose of azithromycin reduces carriage of bacteria , it is unlikely to be beneficial in reducing LOS , duration of O2 requirement or readmissions in children hospitalised with bronchiolitis . It remains uncertain if an earlier and /or longer duration of azithromycin improves clinical and microbiological outcomes for children . The trial was registered with the Australian and New Zeal and Clinical Trials Register . Clinical trials number : ACTRN12608000150347 . http://www.anzctr.org.au/Trial Search .aspx In this double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous setting s globally , high quality evidence to inform management is scarce . It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations , but not all practitioners agree . Inadequately treated exacerbations may risk lung function deterioration . Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis . Methods We are conducting a b ronchiectasis e xacerbation st udy ( BEST ) , which is a multicentre , r and omised , double-blind , double-dummy , placebo-controlled , parallel group trial , in five centres ( Brisbane , Perth , Darwin , Melbourne , Auckl and ) . In the component of BEST presented here , 189 children fulfilling inclusion criteria are r and omised ( allocation-concealed ) to receive amoxicillin-clavulanic acid ( 22.5 mg/kg twice daily ) with placebo-azithromycin ; azithromycin ( 5 mg/kg daily ) with placebo-amoxicillin-clavulanic acid ; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days . Clinical data and a paediatric cough-specific quality of life score are obtained at baseline , at the start and resolution of exacerbations , and at day 14 . In most children , blood and deep nasal swabs are also collected at the same time points . The primary outcome is the proportion of children whose exacerbations have resolved at day 14 . The main secondary outcome is the paediatric cough-specific quality of life score . Other outcomes are time to next exacerbation ; requirement for hospitalisation ; duration of exacerbation ; and spirometry data . Descriptive viral and bacteriological data from nasal sample s and blood markers will also be reported . Discussion Effective , evidence -based management of exacerbations in people with bronchiectasis is clinical ly important . Yet , there are few r and omised controlled trials ( RCTs ) in the neglected area of non-cystic fibrosis bronchiectasis . Indeed , no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist . Our multicentre , double-blind RCT is design ed to determine if azithromycin and amoxicillin-clavulanic acid , compared with placebo , improve symptom resolution on day 14 in children with acute respiratory exacerbations . Our planned assessment of the predictors of antibiotic response , the role of antibiotic-resistant respiratory pathogens , and whether early treatment with antibiotics affects duration and time to the next exacerbation , are also all novel . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) number ACTRN12612000011886 In the CLARICOR trial , significantly increased cardiovascular ( CV ) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin . We report on the impact of statin treatment at entry on the CV and all-cause mortality . The multicenter CLARICOR trial r and omized patients to oral clarithromycin ( 500 mg daily ; n = 2172 ) versus matching placebo ( daily ; n = 2201 ) for 2 weeks . Patients were followed through public data bases . In the 41 % patients on statin treatment at entry , no significant effect of clarithromycin was observed on CV ( hazard ratio [ HR ] , 0.68 , 95 % confidence interval [ CI ] , 0.38 - 1.22 ; P = 0.20 ) or all-cause mortality ( HR , 1.08 ; 95 % CI , 0.71 - 1.65 ; P = 0.72 ) at 2.6-year follow up . In the patients not on statin treatment at entry , clarithromycin was associated with a significant increase in CV ( HR , 1.90 ; 95 % CI , 1.34 - 2.67 ; P = 0.0003 ; statin-clarithromycin interaction P = 0.0029 ) and all-cause mortality ( HR , 1.33 ; 95 % CI , 1.05 - 1.67 ; P = 0.016 ; statin-clarithromycin interaction P = 0.41 ) . Multivariate analysis and 6-year follow up confirmed these results . Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin Purpose Anti-virulence strategies have not been evaluated for the prevention of bacterial infections . Prolonged colonization of intubated patients with Pseudomonas aeruginosa isolates producing high-levels of the quorum sensing (QS)-regulated virulence factor rhamnolipids has been associated with ventilator-associated pneumonia ( VAP ) . In this pathogen , azithromycin reduces QS-regulated virulence . We aim ed to assess whether azithromycin could prevent VAP in patients colonized by rhamnolipids producing isolates . Methods In a r and omized , double-blind , multicenter trial , intubated colonized patients received either 300 mg/day azithromycin or placebo . Primary endpoint was the occurrence of P. aeruginosa VAP . We further identified those patients persistently colonized by isolates producing high-levels of rhamnolipids and therefore at the highest risk to develop VAP linked to this QS-dependent virulence factor . Results Ninety-two patients were enrolled ; 43 azithromycin-treated and 42 placebo patients were eligible for the per- protocol analysis . In the per- protocol population , the occurrence of P. aeruginosa VAP was reduced in the azithromycin group but without reaching statistical significance ( 4.7 vs. 14.3 % VAP , p = 0.156 ) . QS-dependent virulence of colonizing isolates was similarly low in both study groups , and only five patients in each arm were persistently colonized by high-level rhamnolipids producing isolates . In this high-risk subgroup , the incidence of VAP was reduced fivefold in azithromycin versus placebo patients ( 1/5 vs. 5/5 VAP , p = 0.048 ) . Conclusions There was a trend towards reduced incidence of VAP in colonized azithromycin-treated patients . In addition , azithromycin significantly prevented VAP in those patients at high risk of rhamnolipid-dependent VAP , suggesting that virulence inhibition is a promising anti-microbial strategy Over a 9-month period from September of 1991 to May of 1992 , 339 patients were included in a r and omized , double-blind , placebo-controlled study using azithromycin as the prophylactic agent to determine whether it effects a clinical ly meaningful reduction in postoperative surgical infections in plastic surgery . Azithromycin was given as prophylaxis in 171 patients and placebo in 168 patients . The study medication was a single oral dose taken at 8 P.M. the day before surgery . The patients were followed up for a minimum of 4 weeks after surgery . The patients who received wound infection prophylaxis had 5.1 percent infections compared with 20.5 percent in the placebo group ( p = 0.00009 ) . Eighty percent of all wound infections were first seen after discharge , explaining why plastic surgeons might overlook their infectious complications . There was a significant reduction in postoperative complications ( p = 0.04 ) and in the additional use of antibiotics postoperatively ( p = 0.007 ) in the prophylaxis group . Subgroup analysis showed a significant reduction in surgical infections in breast surgery ( p < 0.05 ) and reconstructive surgery with flaps ( p < 0.05 ) . No effect of the prophylactic regime was demonstrated in patients undergoing secondary surgery for cleft lip and palate disease Background Clinical management of primary ciliary dyskinesia ( PCD ) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections , through the administration of antibiotics . Treatment practice s in PCD are largely extrapolated from more common chronic respiratory disorders , particularly cystic fibrosis , but no r and omized controlled trials ( RCT ) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD . Maintenance therapy , with the macrolide antibiotic azithromycin , is currently widely used in chronic respiratory diseases including PCD . In addition to its antibacterial properties , azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties . The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD . The secondary objectives are to evaluate the efficacy of azithromycin on lung function , ventilation inhomogeneity , hearing impairment , and symptoms ( respiratory , sinus , ears and hearing ) measured on a PCD-specific health-related quality of life instrument , and to assess the safety of azithromycin maintenance therapy in PCD . Methods The BESTCILIA trial is a European multi-centre , double-blind , r and omized , placebo-controlled , parallel group study . The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months . Subjects with a confirmed diagnosis of PCD , age 7–50 years , are eligible for inclusion . Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria . The planned number of subjects to be included is 125 . The trial has been approved by the Research Ethics Committees of the participating institutions . Discussion We present a study protocol of an ongoing RCT , evaluating for the first time , the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD . The RCT evaluates azithromycin maintenance therapy , a drug already commonly prescribed in other chronic respiratory disorders . Furthermore , the trial will utilize the Lung clearance index and new , PCD-specific quality of life instruments as outcome measures for PCD . Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection , exacerbations at enrolment , and the patients ’ perception of disease severity and necessity of additional management and treatment during trial participation . Trial registration EudraCT 2013 - 004664 - 58 ( date of registration : 2014 - 04 - 08 ) Background : Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases . The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis . Methods : A multicentre , r and omised , double blind , placebo controlled trial was conducted from October 2001 to June 2003 . The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second ( FEV1 ) of 40 % or more . The active group received either 250 mg or 500 mg ( body weight < or ⩾40 kg ) of oral azithromycin three times a week for 12 months . The primary end point was change in FEV1 . Results : Eighty two patients of mean ( SD ) age 11.0 ( 3.3 ) years and mean ( SD ) FEV1 85 (22)% predicted were r and omised : 40 in the azithromycin group and 42 in the placebo group . Nineteen patients were infected with Pseudomonas aeruginosa . The relative change in FEV1 at month 12 did not differ significantly between the two groups . The number of pulmonary exacerbations ( count ratio 0.50 ( 95 % CI 0.32 to 0.79 ) , p<0.005 ) , the time elapsed before the first pulmonary exacerbation ( hazard ratio 0.37 ( 95 % CI 0.22 to 0.63 ) , p<0.0001 ) , and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status ( count ratio 0.55 ( 95 % CI 0.36 to 0.85 ) , p<0.01 ) . No severe adverse events were reported . Conclusion : Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression , even before infection with Pseudomonas aeruginosa Abstract Background Food residue in the remnant stomach after subtotal gastrectomy ( STG ) interferes with endoscopic observation . We investigated whether intravenous erythromycin improves gastric mucosa visualization in patients with STG . Methods This study was conducted from April 2012 to October 2012 as a double-blinded , placebo-controlled , r and omized trial . Patients who received STG with complete resection ( stage T1–2N0M0 ) were included . Exclusion criteria were diabetes mellitus , neurologic disease , myopathy , recent viral enteritis history , concomitant therapy influencing gastrointestinal motility and severe comorbidity . Patients were instructed to consume a soft diet for dinner between 1800 and 2000 h , and endoscopies were performed between 0900 and 1200 h. Patients were assigned r and omly to receive either erythromycin ( 125 mg in normal saline 50 cc ) or placebo saline . The endoscopy was performed 15 min after infusion . Grade of residual food was rated as follows : G0 , no residual food ; G1 , a small amount of residual food ; G2 , a moderate amount of residual food ; G3 , a moderate amount of residual food that hinders observation of the entire surface , even with body rolling ; G4 , a great amount of residual food such that endoscopic observation is impossible . Results When good visibility was defined as G0+G1 , visibility was significantly better in the erythromycin group ( 61 + 19 % ) than in the placebo group ( 38 + 12 % , p < 0.001 ) . However , this effect was not seen in patients within 6 months after gastrectomy . The risk factor for food stasis in the placebo group ( n = 58 ) was food stasis at last endoscopy . The only factor predicting erythromycin response in the erythromycin group ( n = 56 ) was elapsed time since surgery . Adverse effects included nausea [ 11 ( 19.7 % ) ] and vomiting [ 1 ( 1.8 % ) ] in the erythromycin group and vomiting [ 3 ( 5.2 % ) ] in the placebo group . However , they were transient and tolerable . Conclusions Premedication with erythromycin improves mucosal visualization during endoscopy in patients with STG . ( Clinical Trials registration number : NCT01659619 ) Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease ( COPD ) . As risks and side effects of long-term intervention outweigh the benefits in the general COPD population , the optimal dose , duration of treatment , and target population are yet to be defined . Hospitalization for an acute exacerbation ( AE ) of COPD may offer a targeted risk group and an obvious risk period for study ing macrolide interventions . Methods / design Patients with COPD , hospitalized for an AE , who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter , r and omized , double-blind , placebo-controlled trial ( NCT02135354 ) . On top of a st and ardized treatment of systemic corticosteroids and antibiotics , subjects will be r and omized to receive either azithromycin or placebo during 3 months , at an uploading dose of 500 mg once a day for 3 days , followed by a maintenance dose of 250 mg once every 2 days . The primary endpoint is the time-to-treatment failure during the treatment phase ( ie , from the moment of r and omization until the end of intervention ) . Treatment failure is a novel composite endpoint defined as either death , the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons , or the diagnosis of a new AE after discharge . Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation , with a limited duration and at a low dose , might be effective and safe in the highest risk period during and immediately after the acute event . If proven effective and safe , this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs Background Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis . Bronchopulmonary dysplasia ( BPD ) is a pulmonary disorder which causes significant morbidity and mortality in premature infants . BPD is pathologically characterized by inflammation , fibrosis and impaired alveolar development . The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight ( ≤ 1000 grams ) population . Methods Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit ( level III , regional referral center ) from 9/1/02 - 6/30/03 were eligible for this pilot study . The pilot study was double-blinded , r and omized , and placebo-controlled . Infants were r and omized to treatment or placebo within 12 hours of beginning mechanical ventilation ( IMV ) and within 72 hours of birth . The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study . Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen , to a maximum of 6 weeks . Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation , post-natal steroid use , days of IMV , and mortality . Data was analyzed by intention to treat using Chi-square and ANOVA . Results A total of 43 extremely premature infants were enrolled in this pilot study . Mean gestational age and birth weight were similar between groups . Mortality , incidence of BPD , days of IMV , and other morbidities were not significantly different between groups . Post-natal steroid use was significantly less in the treatment group [ 31 % ( 6/19 ) ] vs. placebo group [ 62 % ( 10/16 ) ] ( p = 0.05 ) . Duration of mechanical ventilation was significantly less in treatment survivors , with a median of 13 days ( 1–47 days ) vs. 35 days ( 1–112 days)(p = 0.02 ) . Conclusion Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants . Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects , before any recommendations regarding routine clinical use can be made Healthy nasal carriers of Staphylococcus aureus were r and omly assigned to one of three treatment regimens : josamycin ( 1.5 g/day ) , erythromycin stearate ( 1.0 g/day ) , or placebo , each administered orally for 7 days . Quantitative nasal cultures were obtained from each subject at intervals before , during , and after treatment . All 25 placebo-treated subjects had positive nasal cultures for S. aureus at all culture intervals . Both josamycin and erythromycin were equally effective in reducing the carrier rates and in decreasing the total numbers of S. aureus isolated from subjects with positive cultures during treatment . No increase in in vitro antibiotic resistance was detected in isolates obtained after therapy . Both antibiotics were well tolerated , and toxicity was not encountered with either drug Outbreaks of Mycoplasma pneumoniae ( MP ) in closed communities can have a high attack rate and can last several months . Azithromycin chemoprophylaxis has not been evaluated as a means of limiting transmission . This r and omized , double-blinded placebo-controlled trial of azithromycin was conducted among asymptomatic hospital employees during an MP outbreak . Oropharyngeal swabs were obtained for detection of MP by polymerase chain reaction , and question naires were administered to assess clinical illness . Of the 147 employees who were enrolled , 73 received azithromycin and 74 received placebo . Carriage was similar within and between groups at weeks 1 and 6 ( 9.6 % vs. 6.7 % and 10.3 % vs. 13.2 % , respectively ) . Four episodes of clinical ly significant respiratory illness occurred in the azithromycin group versus 16 episodes in the placebo group ( protective efficacy , 75 % ; 95 % confidence interval , 28%-91 % ) . Use of azithromycin prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may be of value in reducing clinical illness ABSTRACT Increasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide , while novel therapies have proven both expensive and ineffective . We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia ( VAP ) . Two hundred patients with sepsis and VAP were enrolled in a published r and omized clinical trial ; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days . Long-term mortality was recorded . The hospitalization cost was calculated by direct quantitation of imaging tests , medical interventions , laboratory tests , nonantibiotic drugs and antibiotics , intravenous fluids , and parenteral and enteral nutrition . Quantities were priced by the respective prices defined by the Greek government in 2002 . The primary endpoint was 90-day mortality ; cumulative hospitalization cost was the secondary endpoint . All-cause mortality rates on day 90 were 60 % in the placebo arm and 43 % in the clarithromycin arm ( P = 0.023 ) ; 141 patients were alive on day 28 , and mortality rates between days 29 and 90 were 44.4 % and 17.4 % , respectively ( P = 0.001 ) . The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were € 14,701.10 and € 13,100.50 per patient staying alive , respectively ( P = 0.048 ) . Respective values on day 45 were € 26,249.50 and € 19,303.10 per patient staying alive ( P = 0.011 ) ; this was associated with the savings from drugs other than antimicrobials . It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost . ( This study has been registered at Clinical Trials.gov under registration no. NCT00297674 . BACKGROUND Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis . Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease . Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease ( PAD ) . PATIENTS AND METHODS Five hundred and nine PAD- patients were r and omised to receive either a 3-day course of azithromycin ( 500 mg daily ) or placebo , with 2 years of follow-up . C. pneumoniae serology was determined at baseline . Clinical endpoints were death , coronary events ( myocardial infa rct ion , unstable angina , and /or coronary revascularization procedures ) , cerebral events ( stroke , TIA , and /or carotid endarterectomy ) and peripheral arterial complications ( increased PAD-symptoms with decreased ankle-brachial index ( ABPI , 0.1-point decrease after 12 months ) , and /or peripheral revascularization procedures ) . RESULTS Five hundred and nine patients ( 160 women ) with an atherosclerotic risk factor profile were r and omised , 257 patients to azithromycin and 252 to placebo . Four hundred and forty nine patients ( 88 % ) had intermittent claudication and 60 ( 12 % ) had critical limb ischemia . By 24-month follow up , 182 patients ( 36 % ) developed 252 complications ( 45 deaths , 34 coronary events , 34 cerebral events and 139 peripheral arterial complications ) . C. pneumoniae IgA-titres were associated with the development of cardiovascular events . Nevertheless , the number of complications ( 131 in the azithromycin group vs. 121 in the placebo group ) and the number of patients that developed complications ( 98 ( 38 % ) in the azithromycin vs. 84 ( 33 % ) in the placebo group ) was comparable in both treatment groups . Life table analysis showed no effect of azithromycin on survival or ABPI . CONCLUSION A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD- patients BACKGROUND AND OBJECTIVES : We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor . Here , we aim to assess the effect of the intervention on maternal and neonatal clinical infections . METHODS : This was a double-blind , placebo-controlled r and omized trial . Gambian women in labor were given either an oral dose of azithromycin ( 2 g ) or placebo . Follow-up was conducted for 8 weeks after delivery . RESULTS : From April 2013 to April 2014 , we recruited 829 mothers and their 830 newborns . Sixteen infants died during the follow-up period ( 8 per arm ) . No maternal deaths or serious adverse events related to the intervention were reported . Maternal infections were lower in the azithromycin group ( 3.6 % vs 9.2 % ; relative risk [ RR ] , 0.40 ; 95 % confidence interval [ CI ] , 0.22–0.71 ; P = .002 ) , as was the prevalence of mastitis ( 1.4 % vs 5.1 % ; RR , 0.29 ; 95 % CI , 0.12–0.70 ; P = .005 ) and fever ( 1.9 % vs 5.8 % ; RR , 0.33 ; 95 % CI , 0.15–0.74 ; P = .006 ) . Among newborns , the overall prevalence of infections was also lower in the azithromycin group ( 18.1 % vs 23.8 % ; RR , 0.76 ; 95 % CI , 0.58–0.99 ; P = .052 ) and there was a marked difference in prevalence of skin infections ( 3.1 % vs 6.4 % ; RR , 0.49 ; 95 % CI , 0.25–0.93 ; P = .034 ) . CONCLUSIONS : Azithromycin given to women in labor decreases infections in both women and newborns during the puerperal period . Larger studies design ed to evaluate the effect of the intervention on severe morbidity and mortality are warranted Azithromycin reduces airway inflammation and improves forced expiratory volume in 1 s ( FEV1 ) in chronic rejection or bronchiolitis obliterans syndrome ( BOS ) after lung transplantation ( LTx ) . Azithromycin prophylaxis might prevent BOS . A double-blind r and omised controlled trial of azithromycin ( n = 40 ) or placebo ( n = 43 ) , initiated at discharge and administered three times a week for 2 yrs , was performed in 2005–2009 at the Leuven University Hospital ( Leuven , Belgium ) . Primary end-points were BOS-free and overall survival 2 yrs after LTx ; secondary end-points were acute rejection , lymphocytic bronchiolitis and pneumonitis rate , prevalence of pseudomonal airway colonisation or gastro-oesophageal reflux , and change in FEV1 , airway and systemic inflammation over time . Patients developing BOS were assessed for change in FEV1 with open-label azithromycin . BOS occurred less in patients receiving azithromycin : 12.5 versus 44.2 % ( p = 0.0017 ) . BOS-free survival was better with azithromycin ( hazard ratio 0.27 , 95 % CI 0.092–0.816 ; p = 0.020 ) . Overall survival , acute rejection , lymphocytic bronchiolitis , pneumonitis , colonisation and reflux were comparable between groups . Patients receiving azithromycin demonstrated better FEV1 ( p = 0.028 ) , and lower airway neutrophilia ( p = 0.015 ) and systemic C-reactive protein levels ( p = 0.050 ) over time . Open-label azithromycin for BOS improved FEV1 in 52.2 % patients . No serious adverse events were noted . Azithromycin prophylaxis attenuates local and systemic inflammation , improves FEV1 and reduces BOS 2 yrs after LTx Background The prevalence of chronic suppurative lung disease ( CSLD ) and bronchiectasis unrelated to cystic fibrosis ( CF ) among Indigenous children in Australia , New Zeal and and Alaska is very high . Antibiotics are a major component of treatment and are used both on a short or long-term basis . One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms . However , there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children . This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis . Methods / design We are conducting a multicentre , r and omised , double-blind , placebo controlled clinical trial in Australia and New Zeal and . Inclusion criteria are : Aboriginal , Torres Strait Isl and er , Maori or Pacific Isl and children aged 1 to 8 years , diagnosed with bronchiectasis ( or probable bronchiectasis ) with no underlying disease identified ( such as CF or primary immunodeficiency ) , and having had at least one episode of pulmonary exacerbation in the last 12 months . After informed consent , children are r and omised to receive either azithromycin ( 30 mg/kg once a week ) or placebo ( once a week ) for 12–24 months from study entry . Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records . Secondary outcomes include length and severity of pulmonary exacerbation episodes , changes in growth , school loss , respiratory symptoms , forced expiratory volume in 1-second ( FEV1 ; for children ≥6 years ) , and sputum characteristics . Safety endpoints include serious adverse events . Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored . Data derived from medical records and clinical assessment s every 3 to 4 months for up to 24 months from study entry are recorded on st and ardised forms . Discussion Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations , it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children . Trial registration Australian New Zeal and Clinical Trials Registry : BACKGROUND Elevated antibodies against Chlamydia pneumoniae have been associated with coronary artery disease . In patients undergoing percutaneous coronary angioplasty , we therefore investigated the effect of roxithromycin on symptomatic restenosis and determined antichlamydial antibodies as well as inflammatory and immunological parameters . METHODS A total of 327 patients undergoing coronary angioplasty were r and omized to roxithromycin or placebo and followed-up for 1 year . Antibodies were determined by microimmunofluorescence and enzyme-linked immunosorbent assay ; C-reactive protein , interleukin-10 , tumor necrosis factor-alpha ( TNF-alpha ) , and eotaxin were determined by enzyme-linked immunosorbent assay . RESULTS Although the frequency of restenosis was not affected by roxithromycin ( 25 restenoses vs 32 in the control group ) , antichlamydial antibodies increased during follow-up ( anti-CP IgG + 12 + /- 2 % , P < .001 ) . Concentrations of TNF-alpha and eotaxin increased as well ( TNF-alpha + 9 + /- 1 % and eotaxin + 10 + /- 2 % ) and correlated with antichlamydial antibody concentrations ( TNF-alpha , r = 0.23 , P = .02 ; eotaxin , r = 0.32 , P = .002 ) . CONCLUSIONS Treatment with roxithromycin was not associated with a reduction of symptomatic restenoses . During follow-up , a marked increase in antichlamydial antibodies , TNF-alpha , and eotaxin was observed , suggesting that angioplasty-induced plaque rupture induces a specific immunological response without activation of inflammatory mechanisms as represented by C-reactive protein . Whether this mechanism occurs in all plaque ruptures remains to be determined Objective To determine the st and ard of reporting of harms-related data , in r and omised controlled trials ( RCTs ) according to the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement extension for harms . Design Systematic review . Data sources The Cochrane library , Ovid MEDLINE , Scopus and ISI Web of Knowledge were search ed for relevant literature . Eligibility criteria for selecting studies We included publications of studies that used the CONSORT harms extension to assess the reporting of harms in RCTs . Results We identified 7 studies which included between 10 and 205 RCTs . The clinical areas of the 7 studies were : hypertension ( 1 ) , urology ( 1 ) , epilepsy ( 1 ) , complimentary medicine ( 2 ) and two not restricted to a clinical topic . Quality of the 7 studies was assessed by a risk of bias tool and was found to be variable . Adherence to the CONSORT harms criteria reported in the 7 studies was inadequate and variable across the items in the checklist . Adverse events are poorly defined , with 6 studies failing to exceed 50 % adherence to the items in the checklist . Conclusions Readers of RCT publications need to be able to balance the trade-offs between benefits and harms of interventions . This systematic review suggests that this is compromised due to poor reporting of harms which is evident across a range of clinical areas . Improvements in quality could be achieved by wider adoption of the CONSORT harms criteria by journals reporting RCTs BACKGROUND The relationship between cigarette smoking and periodontal disease has been examined extensively . Local delivery of antimicrobials into periodontal pockets improves periodontal health . The present study is design ed to investigate the adjunctive effects of subgingivally delivered 0.5 % clarithromycin ( CLM ) as an adjunct to scaling and root planing for treating chronic periodontitis in smokers . METHODS Sixty-one patients were r and omized and categorized into two treatment groups : group 1 , in which 31 individuals received scaling and root planing plus 0.5 % CLM , and group 2 , in which 30 individuals received scaling and root planing plus placebo gel . Clinical parameters were recorded at baseline and at 1 , 3 , and 6 months ; they included plaque index ( PI ) , modified sulcus bleeding index ( mSBI ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) . The mean concentration of 0.5 % CLM in gingival crevicular fluid ( GCF ) was estimated by reverse-phase high-performance liquid chromatography . RESULTS Both therapies result ed in significant improvements . At the end of 6 months , the mean GI , PI , mSBI , PD , and CAL for the CLM group were 1.06 ± 0.28 , 2.82 ± 0.64 , 1.36 ± 0.24 , 4.64 ± 0.63 , and 4.90 ± 0.46 , respectively , versus 1.38 ± 0.41 , 3.22 ± 0.57 , 1.44 ± 0.27 , 6.07 ± 0.88 , and 5.69 ± 0.46 , respectively , for the placebo group . Using an individual-based analysis , individuals in group 1 showed enhanced clinical outcome ( P < 0.05 ) over a period of 6 months compared with those in group 2 . CLM was detected in GCF until a period of 7 weeks after the local drug delivery . CONCLUSION Although both treatment strategies seemed to benefit the individuals , the adjunctive use of 0.5 % CLM as a controlled drug delivery system enhanced the clinical outcome OBJECTIVE To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis ( AB ) . STUDY DESIGN We performed a r and omized , double-blinded , placebo-controlled trial in southern Brazil , from 2009 to 2011 . Infants ( < 12 months of age ) hospitalized with AB were recruited in 2 hospitals . Patients were r and omized to receive either azithromycin or placebo , administered orally , for 7 days . At enrollment , clinical data were recorded and nasopharyngeal sample s were collected for viral identification through immunofluorescence . Main outcomes were duration of oxygen requirement and length of hospitalization . RESULTS One hundred eighty-four patients were included in the study ( azithromycin 88 subjects , placebo 96 subjects ) . Baseline clinical characteristics and viral identification were not different between the groups studied . A virus was detected in 112 ( 63 % ) patients , and of those , 92 % were positive for respiratory syncytial virus . The use of azithromycin did not reduce the median number of days of either hospitalization ( P = .28 ) or oxygen requirement ( P = .47 ) . CONCLUSIONS Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB , even when restricting the findings to those with positive respiratory syncytial virus sample s. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance BACKGROUND Along with conventional periodontal surgical therapy , local delivery of antibiotics may provide more effective treatment in smokers by targeting tissue-invasive bacteria . The aim of this r and omized , placebo-controlled , double-masked clinical trial was to evaluate the adjunctive effects of subgingivally delivered 0.5 % azithromycin ( AZM ) as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis in smokers . METHODS Fifty-four patients were r and omized and categorized into two treatment groups : Group 1 - 26 subjects who received ( SRP ) plus placebo gel and Group 2 - 28 subjects who received ( SRP ) plus 0.5 % azithromycin . Clinical parameters were recorded at baseline , 3 , 6 and 9 months . They included Plaque Index ( PI ) , modified Sulcus Bleeding Index ( mSBI ) , probing depth ( PD ) and clinical attachment level ( CAL ) . RESULTS Azithromycin result ed in significant improvements . A single application of AZM result ed in attachment gain at 9 months of 2.44 ± 0.64 mm as compared to 0.18 ± 0.68 mm for the placebo . Similarly , pocket depth and PI were significantly reduced but no change in the mSBI was noted . CONCLUSIONS When compared to the placebo , the adjunctive use of 0.5 % AZM result ed in significant improvement in clinical outcome in the treatment of chronic periodontitis among smokers We attempted to determine whether the administration of erythromycin shortens the period of postoperative ileus by a prospect i ve , double-blind , placebo-controlled study . Seventy-seven patients were r and omized and included in the statistical calculations . The patients were stratified according to the operation performed ( cholecystectomy , celiotomy , or other major abdominal operations ) . Forty-one patients ( group 1 ) received 250 mg erythromycin intravenously every 8 h for nine doses upon admission to the recovery room . Thirty-six patients ( group 2 ) received placebo . The time ( in hours ) to first passage of flatus , first liquid meal , first bowel movement , and total length of hospital stay was recorded . There was no significant difference between group 1 and group 2 in time to first flatus ( 54.9 + /- 29 vs. 53.9 + /- 27 h , respectively ) , first meal ( 70.4 + /- 44 vs. 71.7 + /- 65 ) , first bowel movement ( 81.8 + /- 32 vs. 80.1 + /- 28 ) , or length of hospital stay ( 185.2 + /- 183 vs. 182.1 + /- 163 ) . Erythromycin , in the dosage tested in this study , does not seem to alter clinical parameters of gastrointestinal motility after an abdominal operation . New prokinetic agents may deserve further studies BACKGROUND To determine whether administration of erythromycin ( E ) could facilitate passage of a nasoenteric feeding tube into the duodenum for postpyloric feedings , this r and omized , double-blind , placebo-controlled trial was performed . METHODS Fifty-seven patients were accrued from the surgical intensive care units ( ICUs ) of a tertiary-care university hospital . Patients enrolled were categorized as to the presence or absence of diabetes mellitus ( DM ) . Those patients without DM were then subdivided into those with normal or depressed mental status . The three groups , normal ( NMS ) , depressed mental status ( DMS ) , or diabetes mellitus ( DM ) , were then r and omized independently to receive either E or placebo ( P ) , followed by blind placement of a feeding tube . Tube placement was verified by an abdominal radiograph . RESULTS Overall , the rate of postpyloric placement was 61 % ( 19/31 ) in the E group , significantly better than 35 % ( 9/26 ) in the P group ( p < .05 ) . In patients with NMS , the success rate with E was improved ( 64 % , 9/14 ) compared with that with P ( 9 % , 1/11 ) ( p < .0005 ) . In the DMS group , there was a 50 % success rate ( 6/12 ) with E versus 63 % ( 5/8 ) with P ( not significant [ NS ] ) . In the DM group , 80 % ( 4/5 ) of the patients had placement of the tube in the duodenum with E and 43 % ( 3/7 ) with P ( NS ) . CONCLUSIONS These data suggest that , overall , E is effective in facilitating placement of a nasoenteric feeding tube into the duodenum in ICU patients . It is clearly beneficial in those patients with normal mental status and may be useful in patients with diabetes mellitus Context . Household contacts of patients with pertussis are at increased risk of acquiring infection . Chemoprophylaxis has been recommended to decrease transmission , particularly to young infants who are at increased risk of severe disease . Although epidemiologic investigations of outbreaks have suggested a benefit , there have been no prospect i ve studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis . Objective . To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis . Design . R and omized , double-blind , placebo-controlled study . Setting . Community based . Subjects . All household contacts of 152 children with culture-positive pertussis who provided consent ( n= 362 ) . After withdrawals , there were 135 households with 310 contacts . Exclusions included pregnancy , age < 6 months , already receiving an erythromycin-containing antibiotic , and erythromycin allergy . Interventions . Erythromycin estolate ( 40 mg/kg/day in 3 divided doses ; maximum dose 1 g ) or placebo for 10 days . Nasopharyngeal cultures , pertussis antibodies , and clinical symptoms were assessed before and after treatment . Primary Outcome . Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive forBordetella pertussis . Results . There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups . There were 20 households with secondary culture-positive cases of pertussis ; 4 households in the erythromycin-treated group and 15 in the placebo-treated group ( efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5 % [ 95 % confidence interval : 7.6–88.7 ] ) . However , medication-associated adverse reactions were reported by 34.0 % of erythromycin and 15.7 % of placebo recipients . Conclusions . Under the conditions of this study , erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis Background —Chlamydia pneumoniae ( Cp ) infection has been associated with atherosclerosis and cardiovascular events . There are controversial results regarding the beneficial effects of antibiotic therapy on future cardiovascular end points . Methods and Results —We determined the long-term effect of a 30-day roxithromycin therapy on intima-to-media thickness ( IMT ) progression of the common carotid artery in 272 consecutive Cp-positive and Cp-negative patients with ischemic stroke in a prospect i ve , double-blind , r and omized trial with a follow-up of 4 years . Cp IgG ( ≥1:64 ) or IgA ( ≥1:16 ) antibodies were initially found in 125 ( 46 % ) patients . During the 3 years before antibiotic therapy , Cp-positive patients showed an enhanced IMT progression even after adjustment for other cardiovascular risk factors ( 0.12 [ 0.11 to 0.14 ] versus 0.07 [ 0.05 to 0.09 ] mm/year ; P < 0.005 ) . The 62 Cp-positive patients given roxithromycin showed a reduced IMT progression during the first 2 years compared with the Cp-positive patients without therapy ( 0.07 [ 0.045 to 0.095 ] versus 0.11 [ 0.088 to 0.132 ] mm/year ; P < 0.01 ) . However , IMT progression increased again during the third and fourth year to similar values as before treatment . No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up . Conclusions —The only limited positive impact of antibiotic therapy on early atherosclerosis progression in Cp-positive patients observed in our study may explain the negative results of most antibiotic trials on clinical end points Azithromycin is an azalide antibiotic with excellent in vitro activity against a wide variety of oral bacteria . It has a long half-life , good tissue penetration and is preferentially taken up by phagocytes . We investigated the microbiological efficacy of azithromycin as an adjunct to the non-surgical treatment of adult chronic periodontitis ; its clinical efficacy is dealt with in a separate paper . 46 patients were treated in a double-blind placebo controlled trial . Microbiological assessment of the same periodontal pocket ( initially > 6 mm ) was made at weeks 0 , 2 , 3 , 6 , 10 and 22 . Either azithromycin 500 mg 1 x daily for 3 days or placebo was given at week 2 . Particular attention was paid to the numbers of black pigmented anaerobes and spirochaetes present since these are the most commonly implicated pathogens in periodontal disease . Pigmented anaerobes were significantly reduced at weeks 3 and 6 in patients who received azithromycin compared to placebo and remained lower , although not significantly so , throughout the study . Counts of spirochaetes were significantly reduced throughout the study in patients who received azithromycin compared to placebo . Our microbiological study suggests that azithromycin may be useful as an adjunct in the treatment of periodontal disease Background : Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis ( CF ) . While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial , their use is limited by side effects . Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis , a condition with features in common with the lung disease of CF . Methods : To determine if azithromycin ( AZM ) improves clinical parameters and reduces inflammation in patients with CF , a 3 month prospect i ve r and omised double blind , placebo controlled study of AZM ( 250 mg/day ) was undertaken in adults with CF . Monthly assessment included lung function , weight , and quality of life ( QOL ) . Blood and sputum collection assessed systemic inflammation and changes in bacterial flora . Respiratory exacerbations were treated according to the policy of the CF Unit . Results : Sixty patients were recruited ( 29 men ) of mean ( SD ) age 27.9 ( 6.5 ) years and initial forced expiratory volume in 1 second ( FEV1 ) 56.6 (22.3)% predicted . FEV1 % and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean ( SE ) decline of –3.62 (1.78)% ( p=0.047 ) and –5.73 (1.66)% ( p=0.001 ) , respectively . Fewer courses of intravenous antibiotics were used in patients on AZM ( 0.37 v 1.13 , p=0.016 ) . Median C reactive protein ( CRP ) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group ( p<0.001 ) . QOL improved over time in patients on AZM and remained unchanged in those on placebo ( p=0.035 ) . Conclusion : AZM in adults with CF significantly improved QOL , reduced CRP levels and the number of respiratory exacerbations , and reduced the rate of decline in lung function . Long term AZM may have a significant impact on morbidity and mortality in patients with CF . Further studies are required to define frequency of dosing and duration of benefit Sixty-three otherwise healthy adults with acute productive cough and no clinical evidence of pneumonia were r and omized to receive a ten-day course of erythromycin or placebo . Fifty-seven of these patients returned completed symptom diaries or returned for a two-week follow-up visit . Patients treated with erythromycin reported a more rapid improvement in subjective ratings of cold symptoms , general health , sputum production , and a mean symptom score . Fewer patients in the erythromycin group required cough or cold medications or were congested by day 10 ( P less than .05 ) . The treatment group was also less likely to have purulent sputum ( 9 percent vs 36 percent , P less than .05 ) and abnormal lung examinations ( 0 percent vs 29 percent , P less than .01 ) at a two-week follow-up visit . These results support the use of erythromycin in acute bronchitis Objective : The purpose of this study was to determine if treatment of pregnant women with Chlamydia trachomatis infection would lower the incidence of preterm delivery and /or low birth weight . Methods : Pregnant women between the 23rd and 29th weeks of gestation were r and omized in double-blind fashion to receive either erythromycin 333 mg three times daily or an identical placebo . The trial continued until the end of the 35th week of gestation . Results : When the results were examined without regard to study site , erythromycin had little impact on reducing low birth weight ( 8 % vs. 11 % , P = 0.4 ) or preterm delivery ( 13 % vs. 15 % , P = 0.7 ) . At the sites with high persistence of C. trachomatis in the placebo-treated women , low birth weight infants occurred in 9 ( 8 % ) of 114 erythromycin-treated and 18 ( 17 % ) of 105 placebo-treated women ( P = 0.04 ) and delivery < 37 weeks occurred in 15 ( 13 % ) of 115 erythromycin-treated and 18 ( 17 % ) of 105 placebo-treated women ( P = 0.4 ) . Conclusions : The results of this trial suggest that the risk of low birth weight can be decreased by giving erythromycin to some women with C. trachomatis . Due to the high clearance rate of C. trachomatis in the placebo group , these data do not provide unequivocal evidence that erythromycin use in all C. trachomatis-infected women prevents low birth weight BACKGROUND The ORACLE II trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women in spontaneous preterm labour and intact membranes , without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study II -- was to determine the long-term effects on children after exposure to antibiotics in this clinical situation . METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3196 ( 71 % ) eligible children . Overall , a greater proportion of children whose mothers had been prescribed erythromycin , with or without co-amoxiclav , had any functional impairment than did those whose mothers had received no erythromycin ( 658 [ 42.3 % ] of 1554 children vs 574 [ 38.3 % ] of 1498 ; odds ratio 1.18 , 95 % CI 1.02 - 1.37 ) . Co-amoxiclav ( with or without erythromycin ) had no effect on the proportion of children with any functional impairment , compared with receipt of no co-amoxiclav ( 624 [ 40.7 % ] of 1523 vs 608 [ 40.0 % ] of 1520 ; 1.03 , 0.89 - 1.19 ) . No effects were seen with either antibiotic on the number of deaths , other medical conditions , behavioural patterns , or educational attainment . However , more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav , respectively ( erythromycin : 53 [ 3.3 % ] of 1611 vs 27 [ 1.7 % ] of 1562 , 1.93 , 1.21 - 3.09 ; co-amoxiclav : 50 [ 3.2 % ] of 1587 vs 30 [ 1.9 % ] of 1586 , 1.69 , 1.07 - 2.67 ) . The number needed to harm with erythromycin was 64 ( 95 % CI 37 - 209 ) and with co-amoxiclav 79 ( 42 - 591 ) . INTERPRETATION The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age . The risk of cerebral palsy was increased by either antibiotic , although the overall risk of this condition was low . FUNDING UK Medical Research Council Background Chronic rhinosinusitis ( CRS ) is recognized as a common disease that imposes a big burden on the health system worldwide . There is ongoing evidence of the anti-inflammatory effect of long-term macrolide in the management of patients with CRS . Objective The aim of this r and omized clinical trial was to evaluate the efficacy of long-term consumption of low-dose azithromycin after functional endoscopic sinus surgery . Methods Sixty-six patients who fulfilled the inclusion criteria were r and omly divided into intervention and control groups . The subjects received the st and ard conventional treatment ( fluticasone nasal spray plus normal saline solution irrigation ) or the conventional treatment plus 250 mg of azithromycin on a daily basis for 3 months . Evaluation was made based on the 22-item Sino-Nasal Outcome Test ( SNOT-22 ) immediately before surgery and 3 months after surgery . Results The intervention group showed a statistically significant improvement in SNOT-22 scores after the treatment and a higher percentage change after 3 months of therapy compared with the control group . A significant correlation was found between the percentage change of SNOT-22 scores and smoking in the placebo group . Lund-Mackay scores , patient age , and the duration of symptoms had no significant correlation with the percentage change . Conclusion Treatment with long-term low-dose azithromycin in combination with the conventional therapy could statistically reduce the recurrence rate of CRS symptoms after functional endoscopic sinus surgery , but there was not sufficient evidence to support clinical significance of azithromycin at the investigated dose . Further larger scale trials , along with a longer follow-up period , is needed to evaluate the effectiveness of the therapy BACKGROUND Early enteral feeding has been shown to be beneficial in improving outcome in critically injured trauma patients . Delayed gastric emptying occurs frequently in trauma patients , increasing the time to achieve nutritional goals , and limiting the benefit of early enteral feedings . Intravenous erythromycin is an effective agent for improving gastric motility in diabetics and postgastrectomy patients . The purpose of this study is to determine the effectiveness of erythromycin for improving gastric motility in critically injured trauma patients . METHODS All critically injured patients who received gastric feedings within 72 hours of admission were c and i date s for the study . Those patients who failed to tolerate feedings at 48 hours ( gastric residual > 150 mL ) were eligible for enrollment . Patients were prospect ively assigned to two treatment groups by r and omization to receive either erythromycin ( ERY ) or placebo ( PLA ) . Treatment was continued in patients who tolerated gastric feedings until the feedings were no longer required . Patients with continued intolerance for 48 hours after r and omization were considered failures of therapy and given metoclopramide . RESULTS Sixty-eight patients were enrolled and were well matched for age , sex , and Injury Severity Score . Mortality , intensive care unit length of stay , hospital length of stay , number of ventilator days , and rate of nosocomial infections were similar in each group . There was a significant difference between the ERY group and the PLA group in the amount of feedings tolerated at 48 hours ( 58 % vs. 44 % , p = 0.001 ) . There was no difference in the amount of feedings tolerated ( as a percentage of target goal volume ) throughout the entire duration of the study ( ERY [ 65 % of target ] vs. PLA [ 59 % ] , p = 0.061 ) . Overall success of therapy at 48 hours was 56 % in the ERY group versus 39 % in the PLA group , but this also did not reach statistical significance ( p = 0.22 ) . CONCLUSION Intravenous erythromycin improves gastric motility and enhances early nutritional intake in critically injured patients OBJECTIVE To determine the efficacy of weekly treatment with oral azithromycin for 13 weeks on the severity and resolution of reactive arthritis ( ReA ) . METHODS 186 patients from 12 countries were enrolled in a r and omised , double blind , placebo controlled trial . Inclusion criteria were inflammatory arthritis of < or = 6 swollen joints , and disease duration of < or = 2 months . All patients received a single azithromycin dose ( 1 g ) as conventional treatment for possible Chlamydia infection , and were then r and omly allocated to receive weekly azithromycin or placebo . Clinical assessment s were made at 4 week intervals for 24 weeks . RESULTS 152 patients were analysable ( 34 failed entry criteria ) , with a mean ( SD ) age of 33.8 ( 9.4 ) and duration of symptoms 30.7 ( 17.5 ) days . Mean C reactive protein ( CRP ) was 48 mg/l , and approximately 50 % of those typed were HLA-B27 + , suggesting that the inclusion criteria successfully recruited patients with acute ReA. Treatment and placebo groups were well matched for baseline characteristics . There were no statistical differences for changes in any end point ( swollen and tender joint count , joint pain , back pain , heel pain , physician and patient global assessment s , and CRP ) between the active treatment and placebo groups , analysed on an intention to treat basis or according to protocol completion . The time to resolution of arthritis and other symptoms or signs by life table analyses was also not significantly different . Adverse events were generally mild , but were more commonly reported in the azithromycin group . CONCLUSIONS This large trial has demonstrated that prolonged treatment with azithromycin is ineffective in Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome ( BOS ) 2 years after lung transplantation ( LTx ) . In the current study , we re‐evaluated the long‐term effects of this prophylactic approach in view of the up date d classification system for chronic lung allograft dysfunction ( CLAD ) . A retrospective , intention‐to‐treat analysis of a r and omized controlled trial comparing prophylactic treatment with placebo ( n = 43 ) versus azithromycin ( n = 40 ) after LTx was performed . Graft dysfunction ( CLAD ) , graft loss ( retransplantation , mortality ) , evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject . Following LTx , 22/43 ( 51 % ) patients of the placebo group and 11/40 ( 28 % ) patients of the azithromycin group ever developed CLAD ( p = 0.043 ) . CLAD‐free survival was significantly longer in the azithromycin group ( p = 0.024 ) . No difference was present in proportion of obstructive versus restrictive CLAD between both groups . Graft loss was similar in both groups : 23/43 ( 53 % ) versus 16/40 ( 40 % ) patients ( p = 0.27 ) . Long‐term pulmonary function and functional exercise capacity were significantly better in the azithromycin group ( p < 0.05 ) . Prophylactic azithromycin therapy reduces long‐term CLAD prevalence and improves CLAD‐free survival , pulmonary function , and functional exercise capacity after LTx Background Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants . Infancy is also a critical time for post-natal lung growth and development . Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life . Globally , bronchiolitis is the most common form of acute lower respiratory infections during infancy . Compared with non-Indigenous Australian infants , Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes . Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin , improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis . Methods We are conducting a dual centre , r and omised , double-blind , placebo-controlled , parallel group trial in northern Australia . Indigenous infants ( aged ≤ 24-months , expected number = 200 ) admitted to one of two regional hospitals ( Darwin , Northern Territory and Townsville , Queensl and ) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are r and omised ( allocation concealed ) to either azithromycin ( 30 mg/kg/dose ) or placebo administered once weekly for three doses . Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital . Primary outcomes are ' length of oxygen requirement ' and ' duration of stay , ' the latter based upon being judged as ' ready for respiratory discharge ' . The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital . Descriptive virological and bacteriological ( including development of antibiotic resistance ) data from nasopharyngeal sample s will also be reported . Discussion Two published studies , both involving different patient population s and setting s , as well as different macrolide antibiotics and treatment duration , have produced conflicting results . Our r and omised , placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is design ed to determine whether it can reduce short-term ( and potentially long-term ) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness . If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis , the intervention would lead to improved short term ( and possibly long term ) health benefits .Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : OBJECTIVES The antiinflammatory effect of macrolide antibiotics has been well-established , as has their role in the treatment of certain disorders of chronic airway inflammation . Several studies have suggested that long-term , low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis ; however , these studies have lacked a control group . To date , this effect has not been tested in a r and omized , placebo-controlled study . METHOD The authors conducted a double-blind , r and omized , placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis . Subjects received either 150 mg roxithromycin daily for 3 months or placebo . Outcome measures included the Sinonasal Outcome Test-20 ( SNOT-20 ) , measurements of peak nasal inspiratory flow , saccharine transit time , olfactory function , nasal endoscopic scoring , and nasal lavage assays for interleukin-8 , fucose , and a2-macroglobulin . RESULTS There were statistically significant improvements in SNOT-20 score , nasal endoscopy , saccharine transit time , and IL-8 levels in lavage fluid ( P<.05 ) in the macrolide group . A correlation was noted between improved outcome measures and low IgE levels . No significant improvements were noted for olfactory function , peak nasal inspiratory flow , or lavage levels for fucose and a2-macroglobulin . No improvement in any outcome was noted in the placebo-treated patients . CONCLUSION These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis , particularly in patients with low levels of IgE , and supports the in vitro evidence of their antiinflammatory activity . Additional studies are required to assess their place in clinical practice BACKGROUND / AIM : Presence of clots in the stomach makes emergency endoscopy difficult in patients with upper gastrointestinal bleeding . We investigated whether the association of erythromycin infusion to gastric lavage could improve stomach cleansing before endoscopy . PATIENTS AND METHODS : One hundred patients admitted for upper gastrointestinal bleeding were r and omly assigned to receive either gastric lavage plus intravenous erythromycin ( 250 mg ) or gastric lavage plus placebo before endoscopy in a double-blind study . The primary end point was the efficacy of intravenous erythromycin to improve stomach cleansing before endoscopy , assessed by both subjective and objective criteria . RESULTS : Characteristics of patients at admission were similar in both groups . Sixty-six patients had portal hypertension . The gastric mucosa was entirely visualized by the endoscopist in 65 % of patients in the erythromycin group , versus 44 % in the placebo group ( p < 0.05 ) . The quality of examination of the upper gastrointestinal tract , assessed by using a 10-cm visual analog scale , was better in the erythromycin group ( 4.2 ± 2 vs. 3.3 ± 2.2 , p < 0.05 ) . Clots were found in the stomach in 30 % of patients in the erythromycin group , versus 52 % in the placebo group ( p < 0.05 ) . However , ability to identify the source of bleeding , mean duration of endoscopy , and need for a second-look endoscopy , did not differ between the two groups . Similar results were observed in the subgroup of cirrhotic patients . Erythromycin was well tolerated by all patients . CONCLUSION : Intravenous erythromycin before endoscopy improves stomach cleansing and quality of endoscopic examination in patients with upper gastrointestinal bleeding , but the clinical benefit is limited BACKGROUND The ORACLE I trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study I -- was to determine the long-term effects on children of these interventions . METHODS We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3298 ( 75 % ) eligible children . There was no difference in the proportion of children with any functional impairment after prescription of erythromycin , with or without co-amoxiclav , compared with those born to mothers who received no erythromycin ( 594 [ 38.3 % ] of 1551 children vs 655 [ 40.4 % ] of 1620 ; odds ratio 0.91 , 95 % CI 0.79 - 1.05 ) or after prescription of co-amoxiclav , with or without erythromycin , compared with those born to mothers who received no co-amoxiclav ( 645 [ 40.6 % ] of 1587 vs 604 [ 38.1 % ] of 1584 ; 1.11 , 0.96 - 1.28 ) . Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced , on specific medical conditions , or on the proportions of children achieving each level in reading , writing , or mathematics at key stage one . INTERPRETATION The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age . FUNDING UK Medical Research Council A double-blind placebo-controlled trial of erythromycin ethylsuccinate was conducted in 65 infants and young children hospitalized with acute nonspecific gastroenteritis . Etiologic agents included rotaviruses ( 29 % ) , Campylobacter jejuni ( 17 % ) , " classical " enteropathogenic Escherichia coli ( 12 % ) , enterotoxigenic E. coli ( 11 % ) , Salmonella ( 9 % ) , Shigella ( 2 % ) , and Giardia lamblia ( 2 % ) . No pathogens were obtained from 25 ( 38 % ) children . Treatment with erythromycin had no effect on the course of the illness in terms of the time required for hydration , stool frequency and temperature to return to normal , or for vomiting to be abolished . Children treated with erythromycin , however , experienced a marginally , but significantly ( P less than 0.05 ) , shorter period of abnormal stool consistency compared with control subjects . This effect was most pronounced in children from whom no enteropathogens were isolated Observational studies have a record of extremely successful contributions to medicine . They are essential for our knowledge about causes and pathogenesis — eg , genetic , environmental , or infectious causes of disease . Additionally , for medical practice we rely on observational studies of prognosis and diagnosis . Nevertheless , over the past years , we have seen recurrent debates about the merit of observational versus r and omised research . The debates have been fuelled recently because of seeming total failures , in which the results of observational studies were completely overturned by r and omised studies . Hormone replacement therapy showed protection from myocardial infa rct ion in observational studies , but a small increase was seen in r and omised trials ; a similar reversal happened for carotene and lung cancer . Such discrepancies raise the question : in what circumstances can observational comparisons be as convincing as r and omised experiments ? To answer that question : I will first recall what is expected from r and omisation . I will then describe two specific issues , adverse effects of drugs and genetic causes of disease , to eluci date under what circumstances evidence from observational research is as good as that from r and omised trials . This description can be generalised to other areas of clinical and epidemiological research , and leads to a proposal for a three-pronged restriction to give observational research the best chance to be as credible as r and omised controlled trials . Benefits of r and omisation Two benefits are expected from r and omisation : unbiased allocation of treatment , because of easier concealment of the allocation scheme , 1 and application of statistical theory on the basis of r and om sampling . AIM To evaluate the effects of systemic azithromycin ( AZM ) as an adjunct to scaling and root planing ( SRP ) in the treatment of generalized chronic periodontitis ( ChP ) . METHODS Forty subjects were r and omly assigned to receive SRP alone or combined with AZM ( 500 mg/day ) for 5 days ( n=20/group ) . Clinical and microbiological examinations were performed at baseline , 6 months and 1-year post-SRP . Nine plaque sample s per subject were analysed by checkerboard DNA-DNA hybridization for 40 bacterial species . Differences between groups were assessed using the Mann-Whitney test and over time using Friedman and Dunn 's tests . RESULTS No statistically significant differences were observed between groups for any parameters evaluated at 1-year post-treatments . Both therapies equally reduced the mean probing depth ( PD ) ( SRP : 3.83 ± 1.92 , AZM : 3.45 ± 1.74 ) and improved the mean clinical attachment ( SRP : 2.35 ± 1.70 , AZM : 2.68 ± 1.76 ) in sites with initial PD7 mm ( primary outcome variable ) between baseline and 1 year . The mean counts and proportions of several periodontal pathogens were reduced , and those of host-beneficial species were increased after treatments . Nonetheless , an important recolonization with red complex species was observed in both groups over the course of the study . CONCLUSION The data of the present study suggest no adjunctive benefit of AZM in the treatment of generalized A r and omised double-blind placebo-controlled study was design ed to evaluate the effects of a semisynthetic macrolide antibiotic , clarithromycin , on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma . Adult asthma patients undergoing treatment with budesonide 400 µg b.i.d . and salbutamol 200 µg p.r.n . less than twice weekly were studied . Arm A ( 16 males/six females , aged 48±16 yrs ) received clarithromycin 250 mg b.i.d . for 8 weeks , arm B ( eight males/12 females , aged 42±12 yrs ) clarithromycin 250 mg t.i.d . and arm C ( six males/15 females , aged 41±16 yrs ) placebo dextrose tablets . Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20 % fall in forced expiratory volume in one second ( PD20 ) . Median ( interquartile range ) PD20 in the three groups before and after treatment with clarithromycin were : arm A : 0.3 ( 0.1–1 ) and 1.3 ( 0.6–2 ) mg ; arm B : 0.4 ( 0.1–0.9 ) and 2 ( 2–2 ) mg ; and arm C : 0.4 ( 0.1–0.9 ) and 0.3 ( 0.1–0.6 ) mg , respectively . Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients . It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma Exacerbations are a hallmark of chronic obstructive pulmonary disease ( COPD ) . Evidence suggests the presence of substantial between-individual variability ( heterogeneity ) in exacerbation rates . The question of whether individuals vary in their tendency towards experiencing severe ( versus mild ) exacerbations , or whether there is an association between exacerbation rate and severity , has not yet been studied . We used data from the MACRO Study , a 1-year r and omized trial of the use of azithromycin for prevention of COPD exacerbations ( United States and Canada , 2006–2010 ; n = 1,107 , mean age = 65.2 years , 59.1 % male ) . A parametric frailty model was combined with a logistic regression model , with bivariate r and om effects capturing heterogeneity in rate and severity . The average rate of exacerbation was 1.53 episodes/year , with 95 % of subjects having a model-estimated rate of 0.47–4.22 episodes/year . The overall ratio of severe exacerbations to total exacerbations was 0.22 , with 95 % of subjects having a model-estimated ratio of 0.04–0.60 . We did not confirm an association between exacerbation rate and severity ( P = 0.099 ) . A unified model , implemented in st and ard software , could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar context s where inference on event time and intensity is considered . We provide SAS code ( SAS Institute , Inc. , Cary , North Carolina ) and a simulated data set to facilitate further uses of this method RATIONALE Patients with refractory asthma have persistent symptoms despite maximal treatment with inhaled corticosteroids and long-acting bronchodilators . The availability of add-on therapies is limited , and effective add-on therapies that target noneosinophilic airway inflammation are needed . Macrolide antibiotics , such as clarithromycin , have in vitro efficacy against IL-8 and neutrophils , key inflammatory mediators in noneosinophilic asthma . OBJECTIVES To determine the efficacy of clarithromycin in patients with severe refractory asthma and specifically in a subgroup of patients with noneosinophilic asthma . METHODS Subjects with severe refractory asthma ( n = 45 ) were r and omized to receive clarithromycin ( 500 mg twice daily ) or placebo for 8 weeks . MEASUREMENTS AND MAIN RESULTS The primary outcome for this study was sputum IL-8 concentration . Other inflammatory outcomes assessed included sputum neutrophil numbers and concentrations of neutrophil elastase and matrix metalloproteinase (MMP)-9 . Clinical outcomes were also assessed , including lung function , airway hyperresponsiveness to hypertonic saline , asthma control , quality of life , and symptoms . Clarithromycin therapy significantly reduced airway concentrations of IL-8 and neutrophil numbers and improved quality -of-life scores compared with placebo . Reductions in neutrophil elastase and MMP-9 concentrations were also observed . These reductions in inflammation were most marked in those with refractory noneosinophilic asthma . CONCLUSIONS Clarithromycin therapy can modulate IL-8 levels and neutrophil accumulation and activation in the airways of patients with refractory asthma . Macrolide therapy may be an important additional therapy that could be used to reduce noneosinophilic airway inflammation , particularly neutrophilic inflammation , in asthma . Clinical trial registered with the Australian Clinical Trials Registry www.actr.org.au ( No. 12605000318684 ) Chlamydia pneumoniae , a common cause of respiratory infection , is vasotropic and frequently found in human atheromas . Whether it plays a causal role in coronary artery disease ( CAD ) is uncertain . The effects of 3 months of azithromycin treatment or placebo were tested in 302 patients with chronic CAD seropositive to C. pneumoniae at 3 - 6 months . Azithromycin reduced a global rank sum score of 4 inflammatory markers ( C-reactive protein [ CRP ] , interleukin [IL]-1 , IL-6 , tumor necrosis factor-alpha ; P=.011 ) and a global rank sum change score ( + /-SD ) ( from 535+/-201 to 587+/-190 ; P=.027 ) at 6 ( but not 3 ) months . Change scores for CRP and IL-6 and median IL-1 levels were lower . C. pneumoniae IgG and IgA antibody titers were unchanged . Clinical cardiovascular events at 6 months did not differ between groups ( azithromycin , 9 ; placebo , 7 ) . Infections were reduced and drug was well tolerated . Thus , azithromycin caused modest but significant reductions in markers of inflammation , but differences in clinical events were not evident at 6 months . However , power was limited and conclusions should await results of the 2-year evaluation and larger studies Abstract Objective To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease . Design Central ly r and omised multicentre trial . All parties at all stages were blinded . Analyses were by intention to treat . Setting Five Copenhagen University cardiology departments and a coordinating centre . Participants 13 702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infa rct ion or angina pectoris in 1993–9 and alive in August 1999 were invited by letter ; 4373 were r and omised . Interventions Two weeks ' treatment with clarithromycin 500 mg/day or matching placebo . Main outcome measures Primary outcome : composite of all cause mortality , myocardial infa rct ion , or unstable angina pectoris during three years ' follow-up . Secondary outcome : composite of cardiovascular mortality , myocardial infa rct ion , or unstable angina pectoris . The outcomes were obtained from Danish registers and were blindly assessed by the event committee . Results 2172 participants were r and omised to clarithromycin and 2201 to placebo . We found no significant effects of clarithromycin on the primary outcome ( hazard ratio 1.15 , 95 % confidence interval 0.99 to 1.34 ) or secondary outcome ( 1.17 , 0.98 to 1.40 ) . Mortality was significantly higher in the clarithromycin arm ( 1.27 , 1.03 to 1.54 ; P = 0.03 ) as a result of significantly higher cardiovascular mortality ( 1.45 , 1.09 to 1.92 ; P = 0.01 ) . Conclusions Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality . The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined . Trial registration Clinical Trials.gov NCT00121550 Aim To evaluate the efficacy of erythromycin to decrease the time and improves the quality of EGD in patients with acute upper GI bleeding . Background The diagnostic and therapeutic value of esophagogastroduodenoscopy ( EGD ) in patients with upper GI bleeding is often limited by the presence of residual blood or clots . Infused erythromycin ( 3 mg/kg ) before EGD , a potent gastro kinetic drug , might improve the quality of EGD in patients with upper GI bleeding and decrease the time of EGD and second- look EGD . Patients and Methods In a prospect i ve , r and omized , double-blind controlled trial , 40 patients with acute upper gastrointestinal bleeding in Taleghani hospital , Tehran , Iran were studied . The patients were r and omized into 2 groups : 1 ) nasogastric tube placement receiving placebo , and 2 ) intravenous erythromycin infusion ( 3mg/kg at 30 min ) combined with nasogastric tube placement . The primary end point was endoscopic yield , as assessed by objective and subjective scoring systems and endoscopic duration . Secondary end points were the need for a second look , blood units transfused , and length of hospital stay and mortality . Results A clear stomach was found more often in the erythromycin group ( 100 % vs. 25 % ; P < 0.001 ) . Erythromycin shortened the endoscopic duration ( 14 vs. 32 minutes in the placebo group ; P < 0.001 ) and reduced the need for second-look endoscopy ( 1 vs. 3 ; P < 0.001 ) , admission duration ( 2 vs 5 ; P < 0.001 ) and reduced the blood units transfused ( 2 vs 4 ; P < 0.001 ) . Conclusion In patients with acute upper GI bleeding , infusion of erythromycin before endoscopy significantly decreases the time and improves the quality of EGD BACKGROUND A previous r and omized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution . The efficacy of clarithromycin was tested in a larger population with sepsis . METHODS Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis , acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind , r and omized , multicentre trial . Clarithromycin ( 1 g ) was administered intravenously once daily for 4 days consecutively in 302 patients ; another 298 patients were treated with placebo . Mortality was the primary outcome ; resolution of infection and hospitalization costs were the secondary outcomes . RESULTS The groups were well matched for demographics , disease severity , microbiology and appropriateness of the administered antimicrobials . Overall 28 day mortality was 17.1 % ( 51 deaths ) in the placebo arm and 18.5 % ( 56 deaths ) in the clarithromycin arm ( P = 0.671 ) . Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died ( 73.1 % ) compared with 15 out of 28 clarithromycin-treated patients ( 53.6 % , P = 0.020 ) . The median time until resolution of infection was 5 days in both arms . In the subgroup with severe sepsis/shock , this was 10 days in the placebo arm and 6 days in the clarithromycin arm ( P = 0.037 ) . The cost of hospitalization was lower after treatment with clarithromycin ( P = 0.044 ) . Serious adverse events were observed in 1.3 % and 0.7 % of placebo- and clarithromycin-treated patients , respectively ( P = 0.502 ) . CONCLUSIONS Intravenous clarithromycin did not affect overall mortality ; however , administration shortened the time to resolution of infection and decreased the hospitalization costs Background Azithromycin prophylaxis has been shown to reduce COPD exacerbations but there is poor evidence for other antibiotics . We compared exacerbation rates in COPD patients with a history of frequent exacerbations ( at least three moderate or severe COPD exacerbations in the past two years ) during a 12-week treatment course and over a subsequent 48-week follow up period . Results 292 patients were r and omised to one of three treatments for 12 weeks : roxithromycin 300 mg daily and doxycycline 100 mg daily ( n = 101 ) ; roxithromycin 300 mg daily ( n = 97 ) ; or matching placebos ( n = 94 ) . There were no differences in the annualised moderate and severe exacerbation rates after treatment with roxithromycin/doxycycline ( 2.83 ( 95 % CI 2.37 - 3.40 ) ) or roxithromycin only ( 2.69 ( 2.26 - 3.21 ) ) compared to placebo ( 2.5 ( 2.08 - 3.03 ) ) ( p = 0.352 and p = 0.5832 respectively ) . Furthermore , there were no differences in the annualised exacerbation rates during 12-week treatment with roxithromycin/doxycycline ( 1.64 ( 95 % CI 1.17 - 2.30 ) ) , roxithromycin only ( 1.75 ( 1.24 - 2.41 ) ) or placebo ( 2.23 ( 1.68 - 3.03 ) ) ( p = 0.1709 and p = 0.2545 respectively ) . There were also no significant differences between groups for spirometry or quality of life scores over either the 12-week treatment or 48-week post-treatment periods . Both active treatments were associated with nausea but otherwise adverse events were comparable among treatment groups . Conclusions Twelve-weeks of prophylaxis with roxithromycin/doxycycline combination or roxithromycin alone did not reduce COPD exacerbations in patients with history of frequent exacerbations . These findings do not support the use of these antibiotics to prevent exacerbations in COPD patients .Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTRN 12615000052538 ) . Date of first registration : 22 January 2015 Background — Evidence has been provided that the atherosclerotic process may be associated with chronic infection with Chlamydia pneumoniae . The effect of antibiotic treatment on peripheral arterial occlusive disease has not been investigated yet . Methods and Results —Forty C pneumoniae seropositive men suffering from peripheral arterial occlusive disease were r and omly assigned to receive either roxithromycin ( 300 mg daily ) or placebo for 28 days . During the 2.7-year follow-up , the number of invasive revascularizations per patient , the walking distance before intervention ( in patients without intervention at study end ) , and the change of carotid plaque size were assessed . Five interventions were performed on 4 patients ( 20 % ) in the roxithromycin group , and 29 interventions were performed on 9 patients ( 45 % ) in the placebo group . Limitation of walking distance to 200 m or less was observed in 4 patients ( 20 % ) in the roxithromycin group and in 13 patients ( 65 % ) in the placebo group . The effect of macrolide treatment on the number of interventions per patient and on preinterventional walking distance was significant . Possible confounding variables such as classical vascular risk factors were excluded by multiple regression analyses . Carotid plaque areas monitored over 6 months decreased in the roxithromycin group ( mean relative value , 94.4 % ) but remained constant in the placebo group ( 100.2 % ) . Regression of carotid plaque size observed in roxithromycin-treated patients was significant for soft plaques . Conclusions —This study indicates that macrolide treatment for 1 month is effective in preventing C pneumoniae seropositive men from progression of lower limb atherosclerosis for several years Background —It has been suggested that infection with Chlamydia pneumoniae ( CPn ) can trigger inflammatory mechanisms that may in turn impair vascular endothelial function . The aim of the present study was to assess whether treatment with the macrolide antibiotic azithromycin improves endothelial function in patients with coronary artery disease and antibodies positive to CPn . Methods and Results —We carried out a r and omized , prospect i ve , double-blind , placebo-controlled trial in 40 male patients ( mean age , 55±9 years ) with documented coronary artery disease and positive CPn-IgG antibody titers . After baseline evaluation , patients were r and omized to receive either azithromycin or placebo for 5 weeks . Flow-mediated dilation ( FMD ) of the brachial artery and E-selectin , von Willebr and factor , and C-reactive protein ( CRP ) levels were assessed at study entry and at the end of the treatment period . Our results showed that patients who received azithromycin had a significant improvement in FMD ( mean change , 2.1±1.1%;P < 0.005 ) . In contrast , FMD was not significantly changed in the placebo group ( mean change , −0.02±0.2 % , P = 0.64 ) . Azithromycin therapy also result ed in a significant decrease of E-selectin and von Willebr and factor levels . CRP levels were not significantly altered by treatment with either azithromycin or placebo . Beneficial effects of azithromycin treatment were independent from the presence of low ( < 1:32 ) or high ( ≥1:32 ) CPn antibody titers . Conclusions —Our findings indicate that treatment with azithromycin has a favorable effect on endothelial function in patients with documented coronary artery disease and evidence of CPn infection irrespective of antibody titer levels . Whether these favorable actions of antibiotic treatment will translate into a beneficial effect on atherogenesis and cardiac events needs further investigation AIMS Mounting evidence suggests infection , specifically Chlamydia pneumoniae , plays a role in atherosclerosis . We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes . Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days . We now report the long-term follow-up results . METHODS AND RESULTS Sixty-four per cent of the initial 202 patients with unstable angina who were r and omly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period . At day 30 , the primary triple and double end-point rates were 9 % and 4 % in the placebo group compared to 2 % and 0 % in the roxithromycin group ( unadjusted P = 0.032 and 0.058 , respectively ) . The secondary triple and double end-point rates were again higher in the placebo group at day 90 ( 12.5 % and 6.25 % vs 4.37 % and 0 % , unadjusted P = 0.065 and 0.029 , respectively ) , and at day 180 ( 14.6 % and 7.29 % vs 8.69 % and 2.17 % , unadjusted P = 0.259 and 0.17 , respectively ) . Anti-C , pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies , with a more significant decrease in the roxithromycin arm ( P = 0.03 ) . Elevated C-reactive protein levels predicted the need for revascularization . CONCLUSIONS In this pilot trial , roxithromycin appears to extend the clinical benefit of preventing death and re-infa rct ion for at least 6 months after initial treatment BACKGROUND Infection with Chlamydia pneumoniae is suspected to contribute to the pathogenesis of human atherosclerosis . We investigated whether treatment with the macrolide antibiotic roxithromycin would reduce mortality or morbidity in patients with an acute myocardial infa rct ion . METHODS AND RESULTS Eight hundred seventy-two patients with an acute myocardial infa rct ion ( AMI ) were r and omly assigned to receive double-blind treatment with either 300 mg roxithromycin or placebo daily for 6 weeks . Primary end point was total mortality during 12-month follow-up . Four hundred thirty-three patients were treated with roxithromycin and 439 with placebo . With the exception of a higher proportion of patients suffering an anterior wall AMI ( 48.1 % in the roxithromycin group versus 40.2 % in the placebo group ; P=0.027 ) and a lower prevalence of chronic obstructive pulmonary disease in the roxithromycin group ( 3.5 % versus 6.9 % , P=0.028 ) , baseline characteristics , reperfusion therapy , and medical treatment were well balanced between the two groups . More patients in the roxithromycin group interrupted their study medication before completion of at least 4 weeks of treatment ( 78 of 433 [ 18 % ] versus 48 of 439 [ 11 % ] ; P=0.003 ; odds ratio , 1.8 ; 95 % CI , 1.2 to 2.6 ) . Follow-up at 12 months was achieved in 868 of 872 ( 99.5 % ) patients . Total mortality at 12 months was 6.5 % ( 28 of 431 ) in the roxithromycin group compared with 6.0 % ( 26 of 437 ) in the placebo group ( odds ratio , 1.1 ; 95 % CI , 0.6 to 1.9 ; P=0.739 ) . There were also no differences in the secondary combined end points at 12 months . CONCLUSIONS Treatment of AMI patients with roxithromycin did not reduce event rates during 12 months of follow-up . Therefore , our findings do not support the routine use of antibiotic treatment with a macrolide in patients with AMI BACKGROUND Bronchiolitis is a major health burden in infants globally , particularly among Indigenous population s. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period . In an international , double-blind r and omized controlled trial , we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis . METHODS Infants aged ≤24 months were enrolled from three centers and r and omized to receive three once-weekly doses of either azithromycin ( 30 mg/kg ) or placebo . Nasopharyngeal swabs were collected at baseline and 48 h later . Primary endpoints were hospital length of stay ( LOS ) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge . Secondary outcomes were : day-21 symptom/signs , respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h. RESULTS Two hundred nineteen infants were r and omized ( n = 106 azithromycin , n = 113 placebo ) . No significant between-group differences were found for LOS ( median 54 h for each group , difference = 0 h , 95 % CI : -6 , 8 ; p = 0.8 ) , time receiving oxygen ( azithromycin = 40 h , placebo = 35 h , group difference = 5 h , 95 % CI : -8 , 11 ; p = 0.7 ) , day-21 symptom/signs , or rehospitalization within 6 months ( azithromycin n = 31 , placebo n = 25 infants , p = 0.2 ) . Azithromycin reduced nasopharyngeal bacterial carriage ( between-group difference 0.4 bacteria/child , 95 % CI : 0.2 , 0.6 ; p < 0.001 ) , but had no significant effect upon virus detection rates . CONCLUSION Despite reducing nasopharyngeal bacterial carriage , three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization . Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis . CLINICAL TRIAL REGISTRATION The trial was registered with the Australian and New Zeal and Clinical Trials Register : Clinical trials number : ACTRN1261000036099 We conducted a r and omized , double-blind , placebo-controlled multicenter trial of azithromycin ( 1,200 mg once weekly ) for the prevention of Mycobacterium avium complex ( MAC ) infection in patients with AIDS and a CD4 cell count of < 100/mm3 . In an intent-to-treat analysis through the end of therapy plus 30 days , nine ( 10.6 % ) of 85 azithromycin recipients and 22 ( 24.7 % ) of 89 placebo recipients developed MAC infection ( hazard ratio , 0.34 ; P = .004 ) . There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough ( first ) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group . Of the 76 patients who died during the study , four ( 10.5 % ) of 38 azithromycin recipients and 12 ( 31.6 % ) of 38 placebo recipients had a MAC infection followed by death ( P = .025 ) . For deaths due to all causes , there was no difference in time to death or number of deaths between the two groups . Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients ( relative risk , 0.49 ; 95 % confidence interval , 0.33 - 0.73 ) . The most common toxic effect noted during the study was gastrointestinal , reported by 78.9 % of azithromycin recipients and 27.5 % of placebo recipients . Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection , death due to MAC infection , and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3 BACKGROUND Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies , its efficacy was tested in patients with sepsis and ventilator-associated pneumonia ( VAP ) . METHODS Two hundred patients with sepsis and VAP were enrolled in a double-blind , r and omized , multicenter trial from June 2004 until November 2005 . Clarithromycin ( 1 g ) was administered intravenously once daily for 3 consecutive days in 100 patients ; another 100 patients were treated with placebo . Main outcomes were resolution of VAP , duration of mechanical ventilation , and sepsis-related mortality within 28 days . RESULTS The groups were well matched with regard to demographic characteristics , disease severity , pathogens , and adequacy of the administered antimicrobials . Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients , respectively ( P = .011 ) ; median times for weaning from mechanical ventilation were 22.5 days and 16.0 days , respectively ( p = .049 ) . Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients , compared with those of placebo-treated patients ( p = .047 ) . Among the 45 patients who died of sepsis , time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients ( p = .004 ) . Serious adverse events were observed in 0 % and 3 % of placebo- and clarithromycin-treated patients , respectively ( P = .25 ) . CONCLUSIONS Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis . The mortality rate at day 28 was not altered . Results are encouraging and render new perspectives on the management of sepsis and VAP There has been inadequate evaluation of an antibiotic for eradication of nontyphoidal salmonellae ( NTS ) in asymptomatic carriers . In a r and omized , placebo-controlled trial , such efficacy was evaluated using 2 five-day regimens ( norfloxacin , 400 mg twice per day , and azithromycin , 500 mg once per day ) compared with placebo . The study included 265 food workers in an area of Thail and where NTS are endemic who were asymptomatic NTS carriers . The presence of NTS in stool sample s was assessed on days 7 , 30 , 60 , and 90 after start of treatment . At each assessment visit , < 4 % of participants in each of the 3 groups carried an initial Salmonella serotype ; 16%-35 % had new Salmonella serotypes detected , except on day 7 in the azithromycin group , when the rate was 4 % . Sanitation was good at work but not at home . Selection of multidrug-resistant Salmonella enterica serotype Schwarzengrund was demonstrated . The study regimens were not better than placebo for treatment of asymptomatic food workers who carried NTS in an area where these organisms are endemic , and use of the regimens result ed in antimicrobial resistance CONTEXT Treatment strategies for cystic fibrosis ( CF ) lung disease include antibiotics , mucolytics , and anti-inflammatory therapies . Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF . OBJECTIVE To determine if an association between azithromycin use and pulmonary function exists in patients with CF . DESIGN AND SETTING A multicenter , r and omized , double-blind , placebo-controlled trial conducted from December 15 , 2000 , to May 2 , 2002 , at 23 CF care centers in the United States . PARTICIPANTS Of the 251 screened participants with a diagnosis of CF , 185 ( 74 % ) were r and omized . Eligibility criteria included age 6 years or older , infection with Pseudomonas aeruginosa for 1 or more years , and a forced expiratory volume in 1 second ( FEV1 ) of 30 % or more . Participants were stratified by FEV1 ( > or = 60 % predicted vs < 60 % predicted ) , weight of less than 40 kg vs 40 kg or more , and CF center . INTERVENTION The active group ( n = 87 ) received 250 mg ( weight < 40 kg ) or 500 mg ( weight > or = 40 kg ) of oral azithromycin 3 days a week for 168 days ; placebo group ( n = 98 ) received identically packaged tablets . MAIN OUTCOME MEASURES Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety . Secondary outcomes included pulmonary exacerbations and weight gain . RESULTS The azithromycin group had a mean 0.097-L ( SD , 0.26 ) increase in FEV1 at day 168 compared with 0.003 L ( SD , 0.23 ) in the placebo group ( mean difference , 0.094 L ; 95 % confidence interval [ CI ] , 0.023 - 0.165 ; P = .009 ) . Nausea occurred in 17 % more participants in the azithromycin group ( P = .01 ) , diarrhea in 15 % more ( P = .009 ) , and wheezing in 13 % more ( P = .007 ) . Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group ( hazard ratio , 0.65 ; 95 % CI , 0.44 - 0.95 ; P = .03 ) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo ( 95 % CI , 0.1 - 1.4 kg ; P = .02 ) . CONCLUSION Azithromycin treatment was associated with improvement in clinical ly relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa Background Macrolides reduce exacerbations in patients with COPD . Their effects on health status has not been assessed as primary outcome and is less clear . This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD - patients with chronic productive cough . Methods In this r and omised controlled trial 84 patients met the eligibility criteria : age of ≥40 years , COPD GOLD stage ≥2 and chronic productive cough . The intervention-group ( n = 42 ) received azithromycin 250 mg 3 times a week and the control-group ( n = 42 ) received a placebo . Primary outcome was cough-specific health status at 12 weeks , measured with the Leicester Cough Question naire ( LCQ ) . Secondary outcomes included generic and COPD -specific health status and exacerbations . Changes in adverse events and microbiology were monitored . Results Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin ( difference 1.3 ± 0.5 , 95 % CI 0.3;2.3 , p = 0.01 ) and met the minimal clinical ly important difference . Similar results were found for the domain scores , and COPD -specific and generic health status question naires . Other secondary endpoints were non-significant . No imbalances in adverse events were found . Conclusions Prophylactic azithromycin improved cough-specific health status in COPD - patients with chronic productive cough to a clinical ly relevant degree . Trial registration Clinical Trials.gov Background —Chlamydia pneumoniae ( Cp ) infection has been associated with atherosclerosis , and a beneficial effect of antibiotic therapy on future cardiovascular events was described . Methods and Results —We evaluated the effect of roxithromycin therapy ( 150 mg twice daily for 30 days ) on the progression of the intima-to-media thickness ( IMT ) of the common carotid artery using duplex ultrasonography in a prospect i ve and r and omized trial with a follow-up of 2 years in 272 consecutive patients with ischemic stroke aged over 55 years in whom the first IMT measurement and Cp testing ( IgG and IgA ) were performed at least 3 years before the roxithromycin treatment . Cp IgG antibodies ( ≥1:64 ) were initially found in 123 ( 45 % ) patients and IgA antibodies ( ≥1:16 ) in 112 ( 41 % ) patients . During the 3 years before antibiotic therapy , Cp-positive patients showed an enhanced IMT progression , even after adjustment for other cardiovascular risk factors ( 0.12 [ 95 % CI , 0.11 to 0.14 ] versus 0.07 [ 0.05 to 0.09 ] mm/year;P < 0.005 ) . The 62 Cp-positive patients given roxithromycin showed a significantly decreased IMT progression after 2 years compared with the Cp-positive patients without therapy ( 0.07 [ 0.045 to 0.095 ] versus 0.11 [ 0.088 to 0.132 ] mm/year;P < 0.01 ) . No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up . No change of IMT was observed in Cp-negative patients given roxithromycin ( n=74 ) compared with those without therapy ( 0.06 [ 0.03 to 0.09 ] versus 0.07 [ 0.05 to 0.09 ] mm/year ) . Conclusions —Our findings suggest a positive impact of antibiotic therapy on early atherosclerosis progression in Cp-seropositive patients with cerebrovascular disease Background : Macrolides have antimicrobial and anti-inflammatory properties that may be useful in the treatment of chronic asthma . Methods : We performed a r and omized , placebo-controlled , double-blinded effectiveness trial of 12 weekly doses of adjunctive azithromycin , with follow-up to 1 year after r and omization , in adults with persistent asthma . Measurements included overall asthma symptoms , asthma quality of life ( AQL ) , and asthma control . Eligible subjects who declined to participate in r and omization were offered enrollment into a parallel open-label ( OL ) azithromycin treatment arm . Results : Of 304 adult asthma patients screened , 97 ( 32 % ) were enrolled : 38 were r and omized to azithromycin , 37 were r and omized to placebo , and 22 opted in as OL subjects . OL subjects had higher rates of severe persistent asthma compared with r and omized subjects ( 32 % vs 8 % , respectively ; P = .012 ) . At 1 year , compared with the placebo arm , subjects r and omized to azithromycin were more likely to have an AQL score ≥1 unit increase compared with baseline , but this difference was not statistically significant ( 36 % vs 21 % for placebo ; P = .335 ) . Compared with placebo , OL subjects had significant improvements in overall asthma symptoms from baseline ( P = .0196 ) , AQL ( P = .0006 ) , and asthma control ( P = .0148 ) . Conclusions : Adults with asthma who were r and omized to azithromycin did not show statistically significant improvement in asthma outcomes , although the study was underpowered to detect clinical improvement in 15 % ( number needed to treat = 7 ) . Adults with severe persistent asthma who elected OL treatment documented clinical improvements in asthma symptoms , AQL , and asthma control that persisted after completion of OL azithromycin ( number needed to treat = 2 ) BACKGROUND Blood in the stomach and esophagus in patients with variceal bleeding often obscures the endoscopic view and makes endoscopic intervention difficult to perform . Erythromycin , a motilin agonist , induces gastric emptying . OBJECTIVE To assess the effect of erythromycin on endoscopic visibility and its outcome in patients with variceal bleeding . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Tertiary care hospital . PATIENTS Adult patients with liver cirrhosis presenting with hematemesis within the previous 12 hours . INTERVENTION Either 125 mg erythromycin or placebo administered intravenously 30 minutes before endoscopy . MAIN OUTCOME MEASUREMENTS Endoscopic visibility during index endoscopy and mean duration of procedure . SECONDARY OUTCOME MEASUREMENTS : Need for repeat endoscopy and blood transfusions within 24 hours , endoscopy-related complications , and length of hospital stay . RESULTS A total of 102 patients received either erythromycin or placebo ( 53 erythromycin and 49 placebo ) . Forty-seven patients in the erythromycin group and 43 in the placebo group had variceal bleeding and were considered for final analysis . A completely empty stomach was seen in 48.9 % of the erythromycin group versus 23.3 % of the placebo group ( P<.01 ) . Mean endoscopy duration was significantly shorter in the erythromycin group than in the placebo group ( 19.0 minutes vs 26.0 minutes , respectively ; P<.005 ) . Length of hospital stay was significantly shorter in the erythromycin group than in the placebo group ( 3.4 days vs 5.1 days , respectively ; P<.002 ) . The need for repeat endoscopy and the mean number of units of blood transfused did not differ significantly in the 2 groups . No adverse events were observed with erythromycin . LIMITATIONS Sample size not sufficient to measure the need for repeat endoscopy and survival benefit . CONCLUSIONS Erythromycin infusion before endoscopy in patients with variceal bleeding significantly improves endoscopic visibility and shortens the duration of the index endoscopy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01060267 . ) We clinical ly evaluated roxithromycin ( ROM ) in a double blind , placebo-controlled , and crossover trial in patients with inflammatory acne . Patients with inflammatory acne who were attending our outpatient clinic for treatment and who had not received topical or systemic treatment for the previous month were enrolled in this study . Patients were r and omly separated into two groups . Group I consisted of 26 patients . The patients received 2x150 mg/day ROM orally in the first period and 2x1 placebo tablets/day in the second period . Group II consisted of 20 patients . These patients received 2x1 placebo tablets/day in the first period and 2x150 mg/day ROM orally in the second period . The first period was the first four weeks , and then there was a washout period of two weeks ( 5th and 6th ) . The second period was the next four weeks ( 7th to 10th weeks ) after the washout period . Median acne scores had clearly decreased in both groups at the end of the study . Differences of median acne scores were statistically significant in both groups between at baseline and at the end of the study ( p<0.001 ) . The results showed that ROM is a safe and effective alternative in the treatment of inflammatory acne with few side effects and good compliance PURPOSE The purpose was to investigate in a large , r and omized , double-blinded , placebo-controlled trial , whether antibiotic treatment can prevent progression of peripheral arterial disease ( PAD ) . MATERIAL AND METHODS Five hundred and seven patients were included ; all patients had an established diagnosis of PAD . Their mean age was 66 years ( 36 - 85 ) , and 59 % were males . Patients were r and omized to Roxithromycin 300 mg daily for 28 days . Baseline investigations were ankle blood pressure , ankle-brachial blood pressure index ( ABPI ) , walking distance , C. pneumoniae serology , cholesterol and medical history . Follow-up was performed every 6 months . Primary events were defined as death , peripheral revascularization and major lower limb amputation . Secondary events were thrombosis , stroke , transient cerebral ischaemic attack and myocardial infa rct ion . Change in ABPI was also investigated . Data were analyzed mainly by Cox regression and linear regression . RESULTS Included patients with PAD were r and omized . Two patients withdrew . Of the remaining , 248 received roxithromycin and 257 placebo . In the treatment group 55 % were seropositive and 53 % in the placebo group . Mean follow-up was 2.1 years ( range 0.06 - 5.1 years ) . In the placebo group , 26 died and 80 primary events occurred in total . In the treatment group , 28 died and 74 primary events were observed . The hazard ratio of death was 1.13 ( 95 % CI : 0.68 ; 1.90 ) , and of primary events 0.92 ( 95 % CI : 0.67 ; 1.26 ) . Also on secondary events and ABPI changes , no significant differences were found . CONCLUSION Long-term treatment with roxithromycin is ineffective in preventing death , amputation , peripheral revascularization , myocardial infa rct ion , stroke , transient cerebral ischaemic attack , thrombosis and decline in ABPI in patients with an established diagnosis of PAD Objective . Our purpose was to determine the effects of erythromycin among hospitalized women with idiopathic preterm labor who were treated with tocolytics . Methods . This prospect i ve r and omized trial was conducted in patients with preterm labor of no clinical ly identifiable cause between 26 and 34 weeks of gestation , who were receiving magnesium sulfate . A total of 136 patients were screened . Of these , 80 eligible , consenting patients were r and omized to receive either 400 mg erythromycin or placebo orally every 6 hours for 10 days . Necessary statistical comparisons were preformed using unpaired two-tailed Student 's t-test and Chi-square analysis . Results . In comparing the 38 erythromycin and 42 placebo patients there was improvement in the treatment-to-delivery interval ( 33.33 ± 18.36 versus 26.88 ± 13.9 days , respectively ) , mean gestational age at delivery ( 36.11 ± 2.33 versus 34.36 ± 2.33 weeks , respectively ) , mean birth weight ( 2722.31 ± 511.65 versus 2419.41 ± 513.54 g , respectively ) , and reduced neonatal admission to NICU ( 36.8 % versus 60.19 % ) in the erythromycin group . Conclusion . In patients with idiopathic preterm labor the adjunctive use of erythromycin therapy appeared safe and well tolerated and result ed in a statistically significant delay from admission to delivery and improved gestational age at delivery , mean birth weight and neonatal outcome BACKGROUND Long-term macrolide treatment has proven benefit in inflammatory airways diseases , but whether it leads to changes in the composition of respiratory microbiota is unknown . We aim ed to assess whether long-term , low-dose erythromycin treatment changes the composition of respiratory microbiota in people with non-cystic fibrosis bronchiectasis . METHODS Microbiota composition was determined by 16S rRNA gene sequencing of sputum sample s from participants in the BLESS trial , a 12-month , double-blind , placebo-controlled trial of twice-daily erythromycin ethylsuccinate ( 400 mg ) in adult patients with non-cystic fibrosis bronchiectasis and at least two infective exacerbations in the preceding year . The primary outcome was within-patient change in respiratory microbiota composition ( assessed by Bray-Curtis index ) between baseline and week 48 , comparing erythromycin with placebo . The BLESS trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12608000460303 . FINDINGS The BLESS trial took place between Oct 15 , 2008 , and Dec 14 , 2011 . Paired sputum sample s were available from 86 r and omly assigned patients , 42 in the placebo group and 44 in the erythromycin group . The change in microbiota composition between baseline and week 48 was significantly greater with erythromycin than with placebo ( median Bray-Curtis score 0·52 [ IQR 0·14 - 0·78 ] vs 0·68 [ 0·46 - 0·93 ] ; median difference 0·16 , 95 % CI 0·01 - 0·33 ; p=0·03 ) . In patients with baseline airway infection dominated by Pseudomonas aeruginosa , erythromycin did not change microbiota composition significantly . In those with infection dominated by organisms other than P. aeruginosa , erythromycin caused a significant change in microbiota composition ( p=0·03 [ by analysis of similarity ] ) , representing a reduced relative abundance of Haemophilus influenzae ( 35·3 % [ 5·5 - 91·6 ] vs 6·7 % [ 0·8 - 74·8 ] ; median difference 12·6 % , 95 % CI 0·4 - 28·3 ; p=0·04 ; interaction p=0·02 ) and an increased relative abundance of P aeruginosa ( 0·02 % [ 0·00 - 0·33 ] vs 0·13 % [ 0·01 - 39·58 ] ; median difference 6·6 % , 95 % CI 0·1 - 37·1 ; p=0·002 ; interaction p=0·45 ) . Compared with placebo , erythromycin reduced the rate of pulmonary exacerbations over the 48 weeks of the study in patients with P. aeruginosa-dominated infection ( median 1 [ IQR 0 - 3 ] vs 3 [ 2 - 5 ] ; median difference -2 , 95 % CI -4 to -1 ; p=0·01 ) , but not in those without P. aeruginosa-dominated infection ( 1 [ 0 - 2 ] vs 1 [ 0 - 3 ] ; median difference 0 , -1 to 0 ; p=0·41 ; interaction p=0·04 ) . INTERPRETATION Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis . In patients without P. aeruginosa airway infection , erythromycin did not significantly reduce exacerbations and promoted displacement of H. influenzae by more macrolide-tolerant pathogens including P. aeruginosa . These findings argue for a cautious approach to chronic macrolide use in patients without P. aeruginosa airway infection . FUNDING Mater Adult Respiratory Research Trust Fund BACKGROUND Erythromycin enhances gastric emptying and has been suggested to facilitate nasoenteric feeding tube placement in adults . Our primary objective was to evaluate the effect of erythromycin on the transpyloric passage of feeding tubes in critically ill children , and second , to evaluate the effect of erythromycin on the distal migration of duodenal feeding tubes . METHODS Seventy-four children were r and omly assigned to receive erythromycin lactobionate ( 10 mg/kg ) IV or equal volume of saline placebo 60 minutes before passage of a flexible weighted tip feeding tube . Abdominal radiographs were obtained 4 hours later to assess tube placement . If the tube was proximal to the third part of the duodenum , two additional doses of erythromycin/placebo were administered 6 hours apart . Those receiving additional doses had repeat radiographs 14 to 18 hours after tube placement . RESULTS The number of postpyloric feeding tubes was similar in the erythromycin and placebo treated groups 4 hours after tube insertion ( 23/37 vs 27/37 , p = .5 ) . Of those with prepyloric tubes at 4 hours , none in the erythromycin group and 3 in the placebo group had the tube migrate to the postpyloric position by 14 to 18 hours ( p < .05 ) . Of those with postpyloric tubes proximal to the third part of the duodenum at 4 hours , additional doses of erythromycin did not cause more tubes to advance further into the intestine than did placebo ( p = .6 ) . CONCLUSIONS Erythromycin does not facilitate transpyloric passage of feeding tubes in critically ill children . The distal migration of duodenal tubes further into the small bowel is also not enhanced by erythromycin The aim of this study was to assess the efficacy of erythromycin , a motilin agonist , in promoting enteral feed tolerance in preterm infants of ±32 wk gestation . Eligible infants were r and omized to receive either low‐dose ( 2.5 mg kg−1 per dose 6 hourly ) oral erythromycin ethylsuccinate or placebo for 10 d from the time of the first oral feed . The data from 22 erythromycin and 21 placebo infants were analysed . Birthweights ( erythromycin 1216 ± 380 g , placebo 1355 ± 228 g , p= 0.25 ) , gestation ( erythromycin 28.6 ± 2.2 wk , placebo 29.3 ± 1.7 wk , p= 0.24 ) and other clinical variables were not different between the groups . Almost all infants were fed expressed breast milk . Erythromycin infants had significantly fewer episodes of large residual gastric aspirates ( > 30 % of the previous 6 h worth of feeds ) over 10 d ( erythromycin 1.1 ± 1.9 , placebo 3.6 ± 2.2 episodes , p= 0.0007 ) . Infants in the erythromycin group achieved full oral feeds more quickly ( 6.0 ± 2.3 vs 7.9 ± 3.5 d , p= 0.04 ) . There were no significant differences between the groups with regard to the number of days on total parenteral nutrition or to the time needed to regain birthweight . One enrolled infant from each group died of necrotizing enterocolitis OBJECTIVE To evaluate the efficacy of a 3-week regimen of erythromycin for treatment of persistent or recurrent nongonococcal urethritis in men . DESIGN A prospect i ve , r and omized , double-blind trial with follow-up at 2 , 4 , and 8 weeks after enrollment . PATIENTS Seventy-seven evaluable men with objective evidence of nongonococcal urethritis ( 36 in the erythromycin group and 41 in the placebo group ) with a mean age of 28 years , a median duration of urethritis of 3 months , and a median number of three previous antimicrobial regimens . INTERVENTION Erythromycin , 500 mg , or placebo four times daily for 3 weeks . RESULTS After 2 weeks of treatment , urethral symptoms resolved in 13 of 25 erythromycin-treated patients compared with 8 of 34 placebo-treated patients ( P = 0.03 ) . Erythromycin also result ed in more frequent resolution of urethral discharge and leukocytosis at all visits compared with placebo but these differences were not statistically significant . First-voided urine leukocyte counts decreased , however , by a median of 89 % ( 95 % CI , -96 % to -67 % ) in the erythromycin group compared with 23 % ( CI , -73 % to 83 % ) in the placebo group after treatment ( P = 0.02 for the difference in changes ) . Further , in men with prostatic inflammation , urinary leukocyte counts decreased by a median of 94 % ( CI , -99 % to -83 % ) after treatment in erythromycin-treated patients compared with a 46 % increase ( CI , -57 % to 290 % ) in placebo-treated patients ( P = 0.0003 for the difference in changes ) . CONCLUSION A 3-week regimen of erythromycin was more effective than placebo in improving symptoms and in reducing pyuria in men with persistent or recurrent nongonococcal urethritis , especially among men with prostatic inflammation In patients with coronary artery disease ( CAD ) , azithromycin therapy is associated with decreased cytokine levels and overall reduction of inflammation . Chlamydia pneumoniae ( C.Pn ) is a common pathogen that may be an important factor in the development and progression of atherosclerosis . Cell-adhesion molecules have an important role in recruitment of inflammatory cells during plaque development and are expressed by endothelial cells on activation . We sought to define the effect of treatment with azithromycin on circulating levels of soluble vascular cell-adhesion molecule ( VCAM-I ) , intercellular adhesion molecule ( ICAM-1 ) , and E-selectin in patients with CAD . Plasma concentrations of VCAM-1 , ICAM-1 , and E-selectin were measured in 40 patients with documented CAD and a positive ( > or = 1:16 ) immunoglobulin G ( IgG ) titer against C.Pn , 20 subjects with normal coronary arteries , and 14 healthy volunteers . Patients were assigned r and omly to receive either 500 mg/wk of azithromycin or placebo for 3 months . Serum sample s were obtained at baseline , at 3 months , and during the follow-up visit at 6 months . Patients with documented CAD exhibited elevation of VCAM-1 ( 535 + /- 227 ng/ ml ; p = 0.0001 ) and E-selectin ( 69 + /- 29 ng/ml ; p = 0.006 ) , but not ICAM-1 ( 321 + /- 65 ng/ml ) concentrations as compared with the patients with angiographically proven normal coronary arteries ( 252 + /- 80 ; 50 + /- 22 ; and 311 + /- 40 ng/ml ) and healthy controls ( 110 + /- 18 ; 29 + /- 2 ; and 238 + /- 47 ng/ml , respectively ) . Prolonged treatment with azithromycin did not significantly affect the plasma levels of soluble VCAM-1 , ICAM-1 , and E-selectin . Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary arteries and healthy controls . Despite substantial heterogeneity in plasma E-selectin , ICAM-1 , and VCAM-1 levels , long-term azithromycin treatment did not affect plasma levels of these adhesion molecules , indicative of endothelial activation , over a period of 6 months OBJECTIVE Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight ( < 2500 gm ) and preterm ( < 37 completed weeks ) birth . STUDY DESIGN In a double-blind clinical trial , 938 carriers of group B streptococci were r and omized to receive erythromycin base ( 333 mg three times a day ) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy . RESULTS Pregnancy outcomes were available for 97 % of r and omized women ; 14 % of subjects withdrew from the trial . Birth weight < 2500 gm occurred in 8.6 % of the erythromycin and 6.1 % of the placebo recipients ( relative risk 1.4 , 0.9 to 2.2 , p = 0.16 ) . Preterm delivery occurred in 11.4 % of women r and omized to erythromycin and in 12.3 % r and omized to placebo ( relative risk 0.9 , 95 % confidence limits 0.6 to 1.3 , p = 0.65 ) . Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance . CONCLUSIONS In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight . Greater than anticipated complicating factors , including spontaneous clearance of the organism , use of nontrial antibiotics , and density of colonization , may have result ed in population sizes too small to detect a benefit of treatment . Future studies should take these factors into account in determining sample sizes BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease ( COPD ) . Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases . METHODS We performed a r and omized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment , resting tachycardia , or apparent risk of prolongation of the corrected QT interval . RESULTS A total of 1577 subjects were screened ; 1142 ( 72 % ) were r and omly assigned to receive azithromycin , at a dose of 250 mg daily ( 570 participants ) , or placebo ( 572 participants ) for 1 year in addition to their usual care . The rate of 1-year follow-up was 89 % in the azithromycin group and 90 % in the placebo group . The median time to the first exacerbation was 266 days ( 95 % confidence interval [ CI ] , 227 to 313 ) among participants receiving azithromycin , as compared with 174 days ( 95 % CI , 143 to 215 ) among participants receiving placebo ( P<0.001 ) . The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group , as compared with 1.83 per patient-year in the placebo group ( P=0.01 ) , and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 ( 95 % CI , 0.63 to 0.84 ; P<0.001 ) . The scores on the St. George 's Respiratory Question naire ( on a scale of 0 to 100 , with lower scores indicating better functioning ) improved more in the azithromycin group than in the placebo group ( a mean [ ±SD ] decrease of 2.8±12.8 vs. 0.6±11.4 , P=0.004 ) ; the percentage of participants with more than the minimal clinical ly important difference of -4 units was 43 % in the azithromycin group , as compared with 36 % in the placebo group ( P=0.03 ) . Hearing decrements were more common in the azithromycin group than in the placebo group ( 25 % vs. 20 % , P=0.04 ) . CONCLUSIONS Among selected subjects with COPD , azithromycin taken daily for 1 year , when added to usual treatment , decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects . Although this intervention could change microbial resistance patterns , the effect of this change is not known . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00325897 . ) Background : No r and omized controlled trial demonstrates the efficacy of erythromycin or metoclopramide in patients with traumatic brain injury ( TBI ) . This study was conducted to determine the efficacy of metoclopramide and erythromycin for improving gastric aspirate volume ( GAV ) in patients with TBI . Material s and Methods : Patients with Glasgow coma score more than 5 admitted to trauma Intensive Care Unit within 72 h of head injury were assessed for eligibility . 115 patients were prospect ively r and omized to receive metoclopramide , erythromycin , or placebo eighth hourly . Gastric feeding intolerance was defined as GAV more than 150 ml with abdominal symptoms . Two consecutive high GAV was defined as feeding failure . Feeding failure was treated by increasing the frequency of dose to 6 hourly in metoclopramide and erythromycin group . Combination therapy with both drugs was given as rescue in the placebo group . Results : Incidence of high GAV was as high as 60.5 % in placebo group . Use of erythromycin was associated with a decrease in the incidence of feeding intolerance to 28.9 % ( P = 0.006 ) . Although feed intolerance decreased to 43.6 % in metoclopramide group , values did not reach statistical significance . The proportion of patients not having high GAV at different days were significantly higher in erythromycin group ( P = 0.027 , log-rank test ) . There was no difference in the proportion of patients not having feeding failure in three groups with increasing number of days . Conclusion : There was a significant decrease in the incidence of high GAV with the use of erythromycin when compared to metoclopramide and placebo ABSTRACT Objective : To evaluate the clinical efficacy , safety , and tolerability of clarithromycin in patients with rheumatoid arthritis . Research design and methods : This was a 6-month , monocenter , r and omized , double-blind , placebo-controlled study . A total of 81 patients with early rheumatoid arthritis were treated with either once-daily oral clarithromycin ( 500 mg ) or daily oral placebo for 6 months . Main outcome measures : The primary efficacy variable was the percentage of patients who had a 20 % improvement according to American College of Rheumatology ( ACR ) criteria ( an ACR 20 response ) at 6 months . Secondary outcome measures were 50 % improvement and 70 % improvement according to ACR criteria ( an ACR 50 response and an ACR 70 response , respectively ) . Results : A significantly greater percentage of patients treated with 500 mg clarithromycin met the ACR 20 response at 6 months compared with patients who received placebo ( 59 vs. 33 % ; p < 0.001 ) . Greater percentages of patients treated with 500 mg clarithromycin also achieved ACR 50 responses ( 34 vs. 10 % ; p < 0.001 ) and ACR 70 responses ( 20 vs. 3 % ; p = 0.003 ) compared with patients who received placebo , respectively . Clarithromycin was well tolerated . There were no dose-limiting toxic effects . Conclusions : In patients with early active rheumatoid arthritis , treatment with clarithromycin significantly improved the signs and symptoms of rheumatoid arthritis . Clarithromycin has been shown to be effective against rheumatoid arthritis OBJECTIVE To determine the efficacy and safety of oral erythromycin ( EM ) for feeding intolerance in preterm infants < 35 weeks gestation . STUDY DESIGN In this r and omized , double-blinded , placebo-controlled trial , preterm infants with feeding intolerance were r and omly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days , followed by 4 mg/kg every 6 hours for another 5 days , or to a control group given placebo . The primary outcome was time to full feeding ( 150 mL/kg/day ) after the start of treatment . RESULTS Each group comprised 23 preterm infants , almost all of whom were < 32 weeks gestation . Baseline characteristics were similar between the 2 groups . Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group ; the respective medians ( interquartile ranges ) were 7 days ( 6 to 9 days ) versus 13 days ( 9 to 15 days ) ( P < .001 ) and 1 episode ( 0 to 2 episodes ) versus 9 episodes ( 2 to 13 episodes ) ( P < .001 ) . No significant differences in episodes of sepsis , necrotizing enterocolitis , and cholestasis were observed . CONCLUSIONS Oral EM was effective and safe for treatment of feeding intolerance in preterm infants OBJECTIVE : To evaluate the efficacy and safety of clarithromycin treatment in preventing bronchopulmonary dysplasia ( BPD ) in Ureaplasma urealyticum – positive preterm infants . PATIENTS AND METHODS : Nasopharyngeal swabs for U urealyticum culture were taken from infants with a birth weight between 750 and 1250 g in the first 3 postnatal days . Infants with a positive culture for U urealyticum were r and omly assigned to 1 of 2 groups to receive either intravenous clarithromycin or placebo . All the patients were followed at least up to the 36th postmenstrual week . RESULTS : A total of 224 infants met the eligibility criteria of the study . Seventy-four ( 33 % ) infants had a positive culture for U urealyticum in the first 3 day cultures . The rate of BPD development was significantly higher in patients with U urealyticum positivity ( 15.9 % vs 36.4 % ; P < .01 ) . However , multivariate logistic regression analysis failed to reveal a significant association between the presence of U urealyticum and BPD development ( odds ratio : 2.4 [ 95 % confidence interval : 0.9–6.3 ] ; P = .06 ) . Clarithromycin treatment result ed in eradication of U urealyticum in 68.5 % of the patients . The incidence of BPD was significantly lower in the clarithromycin group than in the placebo group ( 2.9 % vs 36.4 % ; P < .001 ) . Multivariate logistic regression analysis confirmed the independent preventive effect of clarithromycin for the development of BPD ( odds ratio : 27.2 [ 95 % confidence interval : 2.5–296.1 ] ; P = .007 ) . CONCLUSIONS : Clarithromycin treatment prevents development of BPD in preterm infants who are born at 750 to 1250 g and colonized with U urealyticum Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections ( STIs ) and HIV-1 in a cohort of Nairobi female sex workers ( FSWs ) . A question naire was administered and a medical examination was performed . HIV-negative women were r and omly assigned to either one gram azithromycin or placebo monthly . Mean age of the 318 women was 32 years , mean duration of sex work 7 years and mean number of clients was 4 per day . High-risk behaviour was frequent : 14 % practised anal intercourse , 23 % sex during menses , and 3 % used intravenous drugs . While 20 % reported condom use with all clients , 37 % never use condoms . However , STI prevalence was relatively low : HIV-1 27 % , bacterial vaginosis 46 % , Trichomonas vaginalis 13 % , Neisseria gonorrhoeae 8 % , Chlamydia trachomatis 7 % , syphilis 6 % and cervical intraepithelial neoplasia ( CIN ) 3 % . It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes , including a proposed trial of HIV prevention through STI chemoprophylaxis BACKGROUND Chronic cough is a common clinical problem worldwide . Although many patients have underlying precipitating conditions such as asthma , gastroesophageal reflux , or rhinitis , many remain symptomatic despite treating these conditions . New approaches are needed for the treatment of this group of patients . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to determine whether 250 g of azithromycin three times a week for 8 weeks would affect the Leicester Cough Question naire ( LCQ ) score in 44 patients with treatment-resistant cough . Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes . RESULTS There was a clinical ly important improvement in LCQ score with azithromycin ( mean change , 2.4 ; 95 % CI , 0.5 to 4.2 ) but not placebo ( mean change , 0.7 ; 95 % CI , -0.6 to 1.9 ) , but the between-group difference was not statistically significant ( P = .12 ) . There were no significant between-group differences for any of the secondary outcome measures . Looking at subgroups of responders , there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin ( mean , 6.19 ; 95 % CI , 4.06 to 8.32 ) . CONCLUSIONS Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo . The use of macrolides for treatment-resistant cough can not be recommended from this study , but they may have a place in the treatment of chronic cough associated with asthma ; this is worthy of further investigation . TRIAL REGISTRY WHO International Clinical Trials Registry ; No. : IS RCT N75749391 . URL : http://apps.who.int BACKGROUND Recently , it has been suggested that Chlamydia pneumoniae possibly plays a possible role in the pathogenesis of atherosclerosis . We investigated whether treatment with clarithromycin prior to coronary artery bypass graft ( CABG ) surgery would prevent subsequent cardiovascular events and mortality . METHODS Patients who were scheduled for CABG surgery were r and omly assigned to receive either clarithromycin or placebo until the day of surgery in a double-blind trial . During the 2 years of follow-up , mortality and cardiovascular events were assessed . RESULTS Follow-up at 2 years was achieved for 473 patients . The mean duration of treatment was 16 days . Patient characteristics at baseline were well balanced between the 2 treatment groups . Mortality was equal in the 2 groups : 10 ( 4.2 % ) of 238 patients in the clarithromycin group and 9 ( 3.8 % ) of 235 patients in the placebo group ( relative risk , 1.10 ; 95 % CI , 0.42 - 2.89 ; P=1.0 ) . Also , there were no significant differences in the proportion of patients who experienced cardiovascular events during the follow-up period : 20 ( 8.4 % ) of 238 patients in the clarithromycin group and 19 ( 8.1 % ) of 235 patients in the placebo group ( relative risk , 1.04 ; 95 % CI , 0.55 - 1.98 ; P=1.0 ) . The overall rate of such events was 58 ( 12.3 % ) of 473 patients . CONCLUSIONS Treatment with clarithromycin in patients scheduled for CABG surgery did not reduce the subsequent occurrence of cardiovascular events or mortality during a 2-year follow-up period A r and omized , placebo-controlled trial was conducted to evaluate the efficacy of clarithromycin in the prevention of disseminated Mycobacterium avium complex ( MAC ) infection in patients with AIDS ; special attention was given to the development of clarithromycin resistance . The median time to documented MAC bacteremia was 199 days for placebo-treated patients , 217 days for clarithromycin-treated patients infected with clarithromycin-susceptible MAC , and 385 days for clarithromycin-treated patients infected with clarithromycin-resistant MAC . Most of the patients with clarithromycin-resistant isolates ( 91 % ) had a baseline CD4 T-cell count of < 20/microL , while these low counts occurred in only 25 % of patients having clarithromycin-susceptible breakthrough isolates . The emergence of clarithromycin resistance did not affect the total period of survival . Resistance to clarithromycin in breakthrough MAC isolates emerges most likely when the patient is extremely immunodeficient at the time of initiation of the preventative therapy ABSTRACT Drug tolerability affects compliance . We evaluated the tolerability levels of azithromycin ( 750-mg loading dose plus 250 mg/day ; n = 148 subjects ) , doxycycline ( 100 mg/day ; n = 75 ) , and placebo ( n = 77 ) as prophylaxis against malaria in Indonesian adults over 20 weeks . Self-reported and elicited symptoms , health perception , hearing , hematology , and biochemistry were assessed . The loading dose was well tolerated . The frequencies ( number per person-years [ p-yr ] ) of all daily reported symptoms were similar in the three arms of the study : 40.2/p-yr for azithromycin , 39.7/p-yr for doxycycline , and 38.2/p-yr for placebo . Relative to those who received placebo , azithromycin recipients complained more often of heartburn ( rate ratio = 10.5 [ 95 % confidence interval , 2.8 to 88.1 ] ) , paresthesia ( 2.03 [ 1.08 to 4.24 ] ) , and mild ( 1.55 [ 1.01 to 2.48 ] ) and severe ( 11.2 [ 1.34 to ∞ ] ) itching but less often of fever ( 0.21 [ 0.09 to 0.49 ] ) and tinnitus ( 0.09 [ 0.04 to 0.21 ] ) . Azithromycin recipients showed no evidence of clinical hearing loss or hematologic , hepatic , or renal toxicity . One azithromycin recipient developed an erythematous rash . Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment STUDY OBJECTIVE To determine whether combining erythromycin with ranitidine is more efficacious than erythromycin or established ranitidine-metoclopramide combination in reducing the volume and acidity of gastric aspirate . DESIGN R and omized , double-blind study . SETTING Operating room complex . PATIENTS Eighty ASA physical status I and II patients . INTERVENTION Patients were divided into 4 groups of 20 patients each . All patients received the study medication ( in tablet form ) packed in identical gelatin capsules 60 to 90 minutes before surgery in the premedication room . Patients in group PP were given two placebo tablets ; group EP received erythromycin 250 mg , and placebo ; group ER received erythromycin 250 mg , and ranitidine 150 mg ; and group RM was given ranitidine 150 mg , and metoclopramide 10 mg . MEASUREMENTS After tracheal intubation , gastric fluid was aspirated via orogastric tube , and volume and pH of the aspirate were studied . RESULTS Significantly higher gastric volume occurred in group PP than groups EP , ER , or RM ( P < 0.001 ) . There were no differences in volumes among groups EP , ER , and RM . Gastric pH was significantly lower ( P < 0.001 ) in groups PP and EP than in groups ER and RM . CONCLUSION Erythromycin and ranitidine combination is more efficacious than erythromycin alone in reducing the acidity and volume of gastric fluid . No difference was found between erythromycin-ranitidine and ranitidine-metoclopramide combination This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes . Sixty-five women were r and omly assigned to receive double-blind treatment with either erythromycin base or an identical-appearing placebo three times daily for 7 days . Only women between 23 and 34 completed weeks ' gestation who did not have an indication for delivery were enrolled in the study . Pretreatment microbiologic tests were obtained and women were followed expectantly . Fifty-five women and their newborns completed the protocol and were fully evaluated . Overall , time from rupture of membranes to onset of labor and to delivery was longer , although not significantly , for erythromycin-treated women . Similarly , there was a trend for reduced neonatal intensive care ( level II , p = 0.07 ) . When gestational age at enrollment was controlled , erythromycin treatment of women between 28 to 32 weeks ' gestation was associated with a prolonged interval from enrollment to delivery [ erythromycin : 292 hours ( 5 to 679 ) ; placebo : 54 ( 12 to 323 ) ; p less than 0.044 ] . Fifty percent of erythromycin-treated women between 28 to 32 weeks ' gestation continued their pregnancies at least 13 days after premature rupture of membranes , whereas 50 % of placebo-treated women were delivered of infants within 4 days ( p = 0.02 ) . Erythromycin treatment among women less than 28 and between 33 to 34 weeks ' gestation was not associated with prolonged latency or other changes . There were no differences between erythromycin- and placebo-treated women in the occurrence of clinical ly recognized chorioamnionitis , postpartum endometritis , or neonatal infectious morbidity . In this double-blind , placebo-controlled trial , erythromycin treatment was well tolerated , safe , and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother-newborn pairs with preterm premature rupture of membranes Preterm prelabour rupture of the foetal membranes ( pPROM ) is the most common antecedent of preterm birth and can lead to death , neonatal disease and long‐term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate , but the results were inconclusive . A large , r and omized , multicentre trial was undertaken to try to resolve this issue . In total , 4826 women with pPROM were r and omized to one of four treatments : 325 mg co‐amoxiclav plus 250 mg erythromycin , co‐amoxiclav plus erythromycin placebo , erythromycin plus co‐amoxiclav placebo , or coamoxiclav placebo plus erythromycin placebo , four times daily for 10 d or until delivery . The primary outcome measure was a composite of neonatal death , chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital . The analysis was undertaken by intention to treat . Indications of short‐term respiratory function , chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin . In contrast , the use of co‐amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis BACKGROUND The combination of ranitidine bismuth citrate ( RBC ) and clarithromycin ( CLR ) was compared with each treatment alone for the eradication of H. pylori and healing of duodenal ulcers in patients infected with H. pylori . METHODS This two-phase , r and omized , double-blind , placebo-controlled , multicenter study evaluated 203 patients with an active duodenal ulcer treated with either ( 1 ) RBC 400 mg BID for 4 weeks plus CLR 500 mg TID for the first 2 weeks ; ( 2 ) RBC 400 mg BID for 4 weeks plus placebo TID for the first 2 weeks ; ( 3 ) placebo BID for 4 weeks plus CLR 500 mg TID for the first 2 weeks ; or ( 4 ) placebo BID for 4 weeks plus placebo TID for the first 2 weeks . Patients with healed ulcers after treatment entered a 24-week observation phase for the assessment of H. pylori and ulcer relapse . RESULTS Four-week ulcer healing rates were higher with RBC + CLR ( 71 % ) and RBC alone ( 66 % ) compared with placebo ( 15 % ; p < 0.05 ) and CLR alone ( 49 % ) . H. pylori eradication rates were significantly higher with RBC + CLR ( 86 % ) compared with RBC alone ( 0 % , p < .001 ) or CLR alone ( 24 % , p < .001 ) . Ulcer recurrence rates after 6 months were lower in patients eradicated of H. pylori infection ( 17 % ) compared with patients who remained infected ( 43 % ) . All treatments were well tolerated . CONCLUSIONS Ranitidine bismuth citrate plus clarithromycin is a simple , convenient , and well-tolerated dual therapy regimen that is effective in eradicating H. pylori and healing duodenal ulcers in patients infected with H. pylori . The eradication of H. pylori in patients with healed ulcers significantly reduces the rate of ulcer relapse OBJECTIVES . Pityriasis rosea ( PR ) is a common skin disorder in children . Its cause is unknown . A recent publication reported a 73 % cure rate in patients with PR after treatment with erythromycin . To duplicate this result using a drug with fewer adverse effects and greater biological half-life , we set out to study the effect of azithromycin on PR . Azithromycin is an azalide antibiotic with a spectrum of antimicrobial activity very similar to that of erythromycin . DESIGN . We r and omly assigned 49 children with PR to receive either azithromycin ( 12 mg/kg per day , up to a maximum of 500 mg/day ) for 5 days or a similar-appearing placebo . Study physicians were blinded to patients ' treatment type . Two pediatricians had to agree on the diagnosis of PR before patients could be enrolled . Subjects were seen at follow-up visits 1 , 2 , and 4 weeks after starting treatment . OUTCOME MEASURES . We measured the appearance of new lesions and resolution of lesions . RESULTS . Rates of cure and of partial resolution were similar in the azithromycin and placebo groups . CONCLUSION . Azithromycin does not cure PR Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease . The influence of macrolides on the expansion rate of abdominal aortic aneurysms ( AAAs ) remains unknown . The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs The Azithromycin and Coronary Events Study is a r and omized , double-blind , placebo controlled trial of azithromycin among adults with stable coronary artery disease . The study is based on the hypothesis that infection with Chlamydia pneumoniae may be causally associated with cardiovascular disease and therefore that treatment directed against this organism may reduce the risk of subsequent coronary events . Participants r and omized to treatment will receive 600 mg of azithromycin orally once a week for 1 year and will be followed a mean of 4 years for the composite primary outcome of coronary heart disease death , nonfatal myocardial infa rct ion , hospitalization for unstable angina , and coronary revascularization . Secondary objectives include those related to a better underst and ing of the relationship between antibody titer and inflammatory markers with treatment status and outcome ; therefore , all participants will have blood specimens obtained at enrollment and a r and om 25 % will have additional specimens collected periodically during follow-up Ten institutions participated in a controlled clinical trial in order to evaluate the efficacy of topical meclocycline and erythromycin in comparison to placebo with regard to papulopustular acne . Both drugs had been incorporated in the same galenic formulation that served as placebo . The vehicle employed in this study guaranteed equally favorable drug relies for both preparations . At the end of the trial , 419 patients could be evaluated for efficacy . As impartial criterion for evaluation , the number of inflammatory lesions on the right side of the face was counted before and after three months of treatment . In addition , we recorded the patients ' and physicians ' overall judgment at the end of the study . As compared with placebo , meclocycline as well as erythromycin brought about statistically significant improvement already after two months of treatment . After three months , the results were statistically very highly significant ( p less than 0.001 ) . At any time of the study , there could not be demonstrated any difference between the two groups treated with meclocycline and erythromycin RATIONALE Frequent chronic obstructive pulmonary disease ( COPD ) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation . Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations . OBJECTIVES To determine whether regular therapy with macrolides reduces exacerbation frequency . METHODS We performed a r and omized , double-blind , placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months , with primary outcome variable being the number of moderate and /or severe exacerbations ( treated with systemic steroids , treated with antibiotics , or hospitalized ) . MEASUREMENTS AND MAIN RESULTS We r and omized 109 out patients : 69 ( 63 % ) males , 52 ( 48 % ) current smokers , mean ( SD ) age 67.2 ( 8.6 ) years , FEV1 1.32 ( 0.53 ) L , FEV1 % predicted 50 (18)% . Thirty-eight ( 35 % ) of the patients had three or more exacerbations in the year before recruitment , with no differences between treatment groups . There were a total of 206 moderate to severe exacerbations : 125 occurred in the placebo arm . Ten in the placebo group and nine in the macrolide group withdrew . Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 ( 95 % confidence interval : 0.489 , 0.859 ; P = 0.003 ) and that these patients had shorter duration exacerbations compared with placebo . There were no differences between the macrolide and placebo arms in terms of stable FEV1 , sputum IL-6 , IL-8 , myeloperoxidase , bacterial flora , serum C-reactive protein , or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period . CONCLUSIONS Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population . Clinical trial registered with www . clinical trials.gov ( NCT 00147667 ) Chlamydia pneumoniae ( Cpn ) is a common respiratory pathogen with a biphasic replicative cycle and has a tendency to cause chronic infections . Azithromycin is commonly used for the treatment of Cpn infections , but little is known about the optimal dose and duration of therapy . In this prospect i ve double-blind , r and omized study the effects of azithromycin and placebo were compared regarding longst and ing airway and /or pharyngeal symptoms in patients with chronic Cpn infection . Further , effects on antibody titres and lung function were assessed . 103 patients were treated with either azithromycin 500 mg daily for 5 d , repeated 3 times with a 23-d interval , or placebo . Patients were examined 4 months and 1 y after completed treatment . Evaluation of symptoms showed general improvement and less hawking in patients treated with azithromycin compared to placebo after 4 months , but there was no sustained difference 1 y after completed treatment . The antibody titres remained stable , and there was no influence on lung function . Adverse events , primarily gastrointestinal , were more frequently reported with azithromycin than placebo . In conclusion , azithromycin was effective for reduction of respiratory symptoms in patients with chronic Cpn infection , but prolonged intermittent treatment with high doses did not eradicate the chronic infection BACKGROUND Nearly half of all hospitalized infants with respiratory syncytial virus ( RSV ) lower respiratory tract disease ( LRTD ) are treated with ( parenteral ) antibiotics . The present study was design ed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of hospitalization in mild to moderate RSV LRTD . METHODS Seventy-one patients < or = 24 months of age with a virologically confirmed clinical diagnosis of RSV LRTD were r and omized to azithromycin 10 mg/kg/day ( n = 32 ) or placebo ( n = 39 ) in a multicenter , r and omized , double-blind , placebo-controlled equivalence trial during three RSV seasons ( 2002 - 2004 through 2005 - 2006 ) . Primary endpoint was duration of hospitalization , secondary endpoints included duration of oxygen supplementation and nasogastric tube feeding , course of RSV symptom score , number of PICU referrals and number of patients who received additional antibiotic treatment . Data were analyzed according to the intention-to-treat principle using the Mann-Whitney U-test or chi2 test considering P < 0.05 as statistically significant . RESULTS Included patients were comparable with respect to baseline demographics , clinical characteristics , laboratory and roentgenologic investigations . The mean duration of hospitalization was not significantly different between patients treated with azithromycin or placebo ( 132.0 + /- 10.8 vs. 139.6 + /- 7.7 hr , P = 0.328 ) . Azithromycin was not associated with a stronger resolution of clinical symptoms represented by the RSV symptom score . Four patients were treated with antibiotics after 72 hr , three of them were assigned to placebo ( P = 0.406 ) . CONCLUSIONS Infants and young children with RSV LRTD do not benefit from routine treatment with antibiotics ( IS RCT N number 86554663 ) BACKGROUND Epidemiologic , laboratory , animal , and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis . We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events . METHODS In this r and omized , prospect i ve trial , we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year . The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States . RESULTS The primary end point , a composite of death due to coronary heart disease , nonfatal myocardial infa rct ion , coronary revascularization , or hospitalization for unstable angina , occurred in 446 of the participants who had been r and omly assigned to receive azithromycin and 449 of those who had been r and omly assigned to receive placebo . There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point ( risk reduction , 1 percent [ 95 percent confidence interval , -13 to 13 percent ] ) . There were also no significant risk reductions with regard to any of the components of the primary end point , death from any cause , or stroke . The results did not differ when the participants were stratified according to sex , age , smoking status , presence or absence of diabetes mellitus , or C. pneumoniae serologic status at baseline . CONCLUSIONS A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease Objective : To compare the effectiveness of oral erythromycin versus ursodeoxycholic acid ( UDCA ) treatment in preventing feeding intolerance and liver function abnormalities . Study Design : A prospect i ve , double blind , r and omized , controlled trial in which three groups of preterm infants ( birth weight < 1500 g ) were r and omized to erythromycin ( 12.5 mg kg−1 per day ) , UDCA ( 5 mg kg−1 every 6 h ) or placebo treatment . During the period 352 infants were admitted to our unit of which 75 infants whose parents accepted participation were enrolled in the study . Full enteral feeding or intestinal failure-associated liver disease was considered as the primary outcome measures . Results : Time to achieve full feeding after beginning the treatment was significantly shorter in the erythromycin group ( P=0.014 ) . γ-Glutamyl transpeptidase levels in the placebo group were significantly higher than in the intervention groups ( P=0.001 ) . GTT level was slightly lower in UDCA groups than erythromycin . Conclusion : Oral erythromycin was most effective in facilitating enteral feeding and UDCA was most effective in preventing cholestasis in very low birth weight infants . Prophylactic usage of UDCA could be considered in infants with prolonged parenteral nutrition Abstract Although erythrasma is a superficial skin infection , there is no consensus on the treatment model of erythrasma . Objective : To compare the efficacy of erythromycin , single-dose clarithromycin and topical fusidic acid in the treatment of erythrasma in a double-blind , placebo-controlled , r and omized trial . Methods : Hundred and fifty-one patients over 18 years of age were included in this study . Patients were r and omized and divided into five groups . They received clarithromycin , erythromycin , fusidic acid cream , placebo cream or placebo tablets . Patients were evaluated by Wood 's light reflection scores and the initial score values and the values on the days of 2 , 7 and 14 were compared statistically . Results : According to the mean of Wood 's light reflection scores , the efficacy of fusidic acid cream therapy was significantly higher than other therapies . When the efficacy of clarithromycin and erythromycin therapy was compared , clarithromycin therapy was significantly more effective than erythromycin therapy at 48 h. However , there was no statistical difference on the days of 7 and 14 . Conclusion : Topical fusidic acid proved to be the most effective treatment ; however , clarithromycin therapy may be an alternative regimen in the treatment of erythrasma because of its efficiency and better patient 's compliance BACKGROUND To study the promotility effects of low dose erythromycin on gastric emptying time in a population of normal low birth weight ( LBW ) neonates on breast feeds with or without nutritional supplements and human milk fortifier ( HMF ) . METHOD A r and omised control trial involving 50 neonates was undertaken and they were given 6mg/kg/day of oral erythromycin or placebo in three divided doses for four consecutive days in the first two weeks of life . The gastric emptying time ( GET ) was assessed ultrasonographically by measuring the decrease in the antral cross sectional area ( ACSA ) . The time taken for the ACSA to become half the prefeed value , was taken as t/2 or half GET . The babies were also assessed for pre and post intervention side effects of the drug . The results were analysed using SPSS ver 11.5 . RESULTS The test group showed a significant decrease in GET after the intervention . This effect was mainly seen in the preterm babies as compared to term Small for Gestational Age ( SGA ) babies . The decrease in GET was more in babies born after 34 weeks of gestation as compared to smaller babies . The reduction in GET was seen in babies on breast milk alone and nutritional supplements with breast milk but not when HMF was added . No side effects of the drug were noted . CONCLUSION Low dose erythromycin is a safe way of decreasing gastric emptying in preterm babies born after 34 weeks of gestation in the first two weeks of life BACKGROUND The addition of azithromycin to st and ard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection . We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section . METHODS In this trial conducted at 14 centers in the United States , we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture . We r and omly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo . All the women were also scheduled to receive st and ard antibiotic prophylaxis . The primary outcome was a composite of endometritis , wound infection , or other infection occurring within 6 weeks . RESULTS The primary outcome occurred in 62 women ( 6.1 % ) who received azithromycin and in 119 ( 12.0 % ) who received placebo ( relative risk , 0.51 ; 95 % confidence interval [ CI ] , 0.38 to 0.68 ; P<0.001 ) . There were significant differences between the azithromycin group and the placebo group in rates of endometritis ( 3.8 % vs. 6.1 % , P=0.02 ) , wound infection ( 2.4 % vs. 6.6 % , P<0.001 ) , and serious maternal adverse events ( 1.5 % vs. 2.9 % , P=0.03 ) . There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications ( 14.3 % vs. 13.6 % , P=0.63 ) . CONCLUSIONS Among women undergoing nonelective cesarean delivery who were all receiving st and ard antibiotic prophylaxis , extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ; C/SOAP Clinical Trials.gov number , NCT01235546 . ) Background —Coronary artery disease , an inflammatory disease , may be caused by infection . We investigated whether the antibiotic clarithromycin would reduce morbidity and mortality in patients with acute non – Q-wave coronary syndrome . Methods and Results —Altogether , 148 patients with acute non – Q-wave infa rct ion or unstable angina were r and omly assigned to receive double-blind treatment with either clarithromycin or placebo for 3 months . The primary end point was a composite of death , myocardial infa rct ion , or unstable angina during treatment ; the secondary end point was occurrence of any cardiovascular event during the entire follow-up period ( average 555 days , range 138 to 924 days ) . There was a trend toward fewer patients meeting primary end-point criteria in the clarithromycin group than in the placebo group ( 11 versus 19 patients , respectively ; risk ratio 0.54 , 95 % CI 0.25 to 1.14;P = 0.10 ) . By the end of the entire follow-up , 16 patients in the clarithromycin group and 27 in the placebo group had experienced a cardiovascular event ( risk ratio 0.49 , 95 % CI 0.26 to 0.92;P = 0.03 ) . Conclusions —Clarithromycin appears to reduce the risk of ischemic cardiovascular events in patients presenting with acute non – Q-wave infa rct ion or unstable angina . No signs of this effect diminishing were observed during follow-up The association observed between coronary heart disease ( CHD ) and Chlamydia ( Chlamydophila ) pneumoniae antibodies prompted , during the 1990s , several primary and secondary prevention trials with various antibiotics . In our CLARICOR trial , a r and omized placebo-controlled trial in 4372 patients with stable CHD , a brief clarithromycin regimen was followed , unexpectedly , by increased long-term mortality . We now compare C. pneumoniae antibody levels at entry with population levels , with the patients ' individual histories , and with their subsequent outcomes . IgG antibody levels were somewhat raised , but elevated IgA and IgG titers were unrelated to entry data ( including prior acute myocardial infa rct ion ) , except for an association with smoking and with not using statins . Hazards of mortality and of other outcomes tended to slightly increase with IgA and decrease with IgG titers , but the unfavorable clarithromycin effect was unrelated to antibody levels and remains unexplained . Smoking-related lung disease probably underlies the link between heart disease and increased IgG titers Background & Aims : Feeding intolerance because of functional gastrointestinal dysmotility and parenteral nutrition-associated cholestasis ( PNAC ) are common problems in preterm , very-low-birth-weight ( VLBW ) infants . This double-blind , r and omized , placebo-controlled study aim ed to assess the effectiveness of “ high-dose ” oral erythromycin as a prokinetic agent in decreasing the incidence of PNAC . Two secondary end points , including the time to achieve full enteral feeding and the duration of parenteral nutrition , were also evaluated . Methods : Infants consecutively admitted to the neonatal unit were r and omized to receive erythromycin ( 12.5 mg/kg/dose every 6 hours for 14 days ) or an equivalent volume of normal saline ( placebo ) if they attained less than half the total daily fluid intake ( < 75 mL/kg/day ) as milk feeds on day 14 of life . Results : Of 182 VLBW infants enrolled , 91 received erythromycin . The incidence of PNAC was significantly lower in erythromycin-treated infants ( 18/91 ) compared with placebo infants ( 37/91 ; P = .003 ) . Treated infants achieved full enteral nutrition significantly earlier ( mean , 10.1 ; SE , 1.7 days ; P < .001 ) , and the duration of parenteral nutrition was also significantly decreased by 10 days ( P < .001 ) . Importantly , fewer infants receiving erythromycin had 2 or more episodes of septicemia ( n = 4 ) compared with placebo patients ( n = 13 , P = .03 ) . No serious adverse effect was associated with erythromycin treatment . Conclusions : High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded BACKGROUND Preterm birth after spontaneous preterm labour is associated with death , neonatal disease , and long-term disability . Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results . We did a r and omised multicentre trial to resolve this issue . METHODS 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were r and omly assigned 250 mg erythromycin ( n=1611 ) , 325 mg co-amoxiclav ( 250 mg amoxicillin and 125 mg clavulanic acid ; n=1550 ) , both ( n=1565 ) , or placebo ( n=1569 ) four times daily for 10 days or until delivery , whichever occurred earlier . The primary outcome measure was a composite of neonatal death , chronic lung disease , or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo ( erythromycin 90 [ 5.6 % ] , co-amoxiclav 76 [ 5.0 % ] , both antibiotics 91 [ 5.9 % ] , vs placebo 78 [ 5.0 % ] ) . However , antibiotic prescription was associated with a lower occurrence of maternal infection . INTERPRETATION This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection BACKGROUND The study stemmed from an incidental observation of improvement in 2 patients with pityriasis rosea while receiving erythromycin . OBJECTIVE The purpose of the study was to evaluate the efficacy of erythromycin in patients with pityriasis rosea . METHODS A double-blind , placebo-controlled clinical study was performed in an outpatient setting in a major hospital . Ninety patients over a period of 2 years were alternatively assigned to treatment group or placebo group . Patients in the treatment group received erythromycin in divided doses for 14 days . The response was categorized as complete response , partial response , or no response . All patients were followed up for 6 weeks . RESULTS Both groups were comparable with regard to age at presentation , sex , and average duration of disease at the time of reporting to the clinic . Upper respiratory tract infection before the appearance of skin lesions was reported in 68.8 % of all patients . Complete response was observed in 33 patients ( 73.33 % ) in the treatment group and none in the placebo group ( P < .0001 ) . CONCLUSION Oral erythromycin was effective in treating patients with pityriasis rosea Die Ergebnisse verschiedener Studien zur Prävention kardiovaskulärer Ereignisse mittels Beh and lung durch Makrolid-Antibiotika die gegen eine C. pneumoniae Infektion gerichtet sind , waren kontrovers . Die vorliegende Arbeit untersucht verschiedene Testsysteme zum Nachweis einer C. pneumoniae Infektion sowie den Effekt einer Beh and lung mit Roxithromycin bei Patienten nach einem akuten Myokardinfarkt ( AMI ) in Abhängigkeit von ihrem Serostatus gegen C. pneumoniae . Wir analysierten das Blut von 160 Patienten der prospektiven r and omisierten doppelblinden ANTIBIO-tische Therapie beim AMI ( ANTIBIO- ) Studie , die den Effekt einer Therapie mit Roxithromycin 300 mg/die über 6 Wochen bei Patienten mit AMI untersuchte . Anti-Chlamydia IgG- , IgA- , and IgM-Antikörper wurden mittels verschiedener Testsysteme bestimmt . Wir f and en eine gute Korrelation zwischen den beiden IgG und IgA Bestimmungs method en ( r = 0,900 , p < 0,001 und r = 0,878 , p < 0,001 ) , wobei es jedoch starke Unterschiede in der Prävalenz positiver Testergebnisse gab . Das führte zu nur moderaten Werten in der Konkordanzanalyse , ausgedrückt durch den Kappa Koeffizienten , für IgG κ = 0,611 ( 95 % CI = 0,498– 0,724 , p < 0,001 ) und für IgA κ = 0,431 ( 95 % CI : 0,322–0,540 , p < 0,001 ) . Wir f and en keine Assoziation zwischen positiven C. pneumoniae Titern und der klinischen Ereignisrate während der 12-Monats-Nachbeobachtungsphase . Auch Patienten mit positiven C. pneumoniae Titern profitierten nicht von einer Roxithromycin Therapie ( p = ns ) . In Abhängigkeit vom verwendeten Testsystem ergeben sich deutliche Unterschiede in der Prävalenz C. pneumoniae seropositiver Patienten . Die klinische Ereignisrate während der Nachbeobachtungszeit wurde weder durch den Serostatus gegen C. pneumoniae der Patienten , noch durch eine Beh and lung mit Roxithromycin , unabhängig vom Serostatus , beeinflusst . Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial . This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infa rct ion ( AMI ) in relation to their serostatus against C. pneumoniae . We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO- ) study , a prospect i ve , r and omised , placebo-controlled , double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI . Anti-Chlamydia IgG- , IgA- , and IgM-antibodies of these patients were analysed by means of different test systems . There was a good correlation between the two IgG and IgA methods ( r = 0.900 , p < 0.001 and r = 0.878 , p < 0.001 , respectively ) , but marked differences in the prevalence of positive tests . This result ed in only moderate concordance values , as expressed by the Kappa coefficients , for IgG κ = 0.611 ( 95 % CI = 0.498–0.724 , p < 0.001 ) and for IgA κ = 0.431 ( 95 % CI : 0.322–0.540 , p < 0.001 ) . No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found . In all test systems used , patients with positive anti-C. pneumoniae titers did not benefit from roxithromycin therapy ( p = ns ) . Depending on the test system used , there are large differences in the prevalence of anti-C. pneumoniae seropositive patients . Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events , independently of the serostatus against C. pneumoniae . However , the power of this subgroup analysis was low to detect small but significant differences BACKGROUND Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment . AIM A r and omized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea . METHODS Seventy patients of pityriasis rosea were given either azithromycin ( n=35 ) or placebo ( n=35 ) and were followed-up at 2 , 4 and 6 weeks . Pruritus was assessed in both groups using the visual analogue scale ( VAS ) . Change in the pityriasis rosea severity score ( PRSS ) and in the VAS were recorded as outcome measures and were compared statistically . RESULTS The decrease in PRSS from baseline through 2 , 4 and 6 weeks within both treatment ( P<0.001 ) and placebo ( P<0.001 ) arms was found to be statistically significant ; however , this change was not significantly different in the two groups ( P=0.179 ) . Similarly , the decrease in VAS was found to be statistically significant within both groups ( P<0.001 ) ; however , the change was comparable between the two groups ( P<0.937 ) . Analysis by Fisher 's exact test did not find a significant difference between the two groups for PRSS and VAS . CONCLUSION Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice ABSTRACT Several small clinical trials have indicated that antibiotic treatment of Chlamydia pneumoniae infection is associated with a better outcome in patients with coronary artery disease ( CAD ) . It has not been demonstrated whether antibiotic treatment eradicates C. pneumoniae from vascular tissue . The aim of the present study was to assess the effect of clarithromycin on the presence of C. pneumoniae in the vascular tissue of patients with CAD . Patients who had CAD and who were waiting for coronary artery bypass graft surgery were enrolled in a r and omized , double-blind , placebo-controlled trial . Patients were treated with clarithromycin at 500 mg or placebo once daily from the day of inclusion in the study until surgery . Several vascular tissue specimens were obtained during surgery . The presence of C. pneumoniae in vascular tissue specimens was examined by immunohistochemical staining ( IHC ) and two PCR assays . Chlamydia immunoglobulin G ( IgG ) titers were determined by an enzyme-linked immunosorbent assay at the time of inclusion in the study and 8 weeks after surgery . A total of 76 patients were included , and 180 vascular tissue specimens were obtained ( 80 specimens from the group treated with clarithromycin and 100 specimens from the group treated with placebo ) . Thirty-five patients received clarithromycin ( mean duration , 27 days ; st and ard deviation [ SD ] , 12.2 days ) , and 41 patients received placebo ( mean duration , 27 days ; SD , 13.9 days ) . IHC detected the C. pneumoniae major outer membrane protein antigen in 73.8 % of the specimens from the group treated with clarithromycin and 77.0 % of the specimens from the group treated with placebo ( P was not significant ) . Chlamydia lipopolysaccharide antigen was found in only one specimen from the group that received placebo . C. pneumoniae DNA was not detected in any specimen . Baseline Chlamydia-specific IgG titers were equally distributed in both groups and were not significantly different after treatment . There was no indication of an active C. pneumoniae infection in vascular tissue . Chlamydia-specific IgG titers remained unchanged throughout the study in both the antibiotic- and the placebo-treated patients OBJECTIVES /HYPOTHESIS The efficacy of macrolides in chronic rhinosinusitis ( CRS ) is still under controversy . To date , only two double-blind , placebo-controlled studies have been published with differing results . None of these studies investigated the possible benefit of macrolides in the postoperative period . We conducted an investigator-initiated clinical trial using 250-mg erythromycin once a day over a period of 3 months , beginning the administration of either erythromycin or placebo 2 weeks after a surgical intervention for CRS . STUDY DESIGN R and omized double-blind , placebo-controlled trial . METHODS The concentrations of eosinophilic cationic protein ( ECP ) and myeloperoxidase in nasal secretion were chosen as primary outcome measures . Additionally , as a secondary outcome measure , changes in the Sino-Nasal Outcome Test-20 score , olfaction , saccharin transit time , nasal endoscopy score , and self-rating of nasal health using a visual analogue scale were evaluated . RESULTS Sixty-seven patients after surgery for CRS with or without nasal polyps were screened , and 58 patients were r and omized to the study groups . For the primary outcomes , the concentrations of ECP changed from 176.4 µl/l ± 79.0 to 226.1 µl/l ± 200.6 in the erythromycin group and from 186.9 µl/l ± 36.0 to 192.9 µl/l ± 189.2 in the placebo group ; no statistical differences were found . Of the secondary outcomes , only the nasal endoscopy score showed a statistically significant improvement in the erythromycin group ( from 2.6 ± 1.4 to 1.9 ± 1.5 points ) compared to the placebo group ( from 2.5 ± 1.3 to 2.6 ± 1.5 points ) . The subgroup of patients without nasal polyps in the erythromycin group showed a tendency to improvement in some secondary outcome criteria . CONCLUSIONS A general recommendation for long-term , low-dose erythromycin treatment after surgery for CRS can not be given . In patients with CRS without nasal polyps , a tendency to improved parameters was detected . LEVEL OF EVIDENCE Ib OBJECTIVE This study aim ed to evaluate clinical and microbiological effects of systemic azithromycin ( AZM ) in adjunct to nonsurgical periodontal therapy ( NSPT ; or scaling root planing - SRP ) in treatment of Aggregatibacter actinomycetemcomitans associated periodontitis ( AAAP ) . METHODS AND MATERIAL S Seventy individuals with moderate to severe periodontitis and subgingival detection of A. actinomycetemcomitans were r and omly allocated to two groups . Thirty-five individuals were allocated to full mouth SRP+AZM ( 500 mg oral delivery ( OD ) × 3 days ) while 35 individuals were allocated to SRP+Placebo ( OD × 3 days ) group . The clinical variables evaluated were probing depth ( PD ) , clinical attachment level ( CAL ) , gingival index ( GI ) , plaque index ( PI ) , and percent bleeding on probing sites ( % BOP ) , while microbiologic variables included percentage of subjects positive for A. actinomycetemcomitans at baseline , 3 , 6 , and 12 months . RESULTS The AZM group showed statistically significant reduction in mean PD ( 2.91 ± 0.88 mm ) as compared to placebo ( 1.51 ± 0.98 mm ) ( P < 0.001 ) , while CAL gain was significant in the AZM group ( 2.71 ± 1.15 mm ) as compared to the placebo group ( 1.71 ± 1.29 mm ) ( P < 0.001 ) . There was also a statistically significant reduction in the number of subjects positive for A. actinomycetemcomitans in the AZM group ( P < 0.0001 ) . CONCLUSION Azithromycin was found to significantly improve the clinical and microbiological parameters in AAAP individuals Women in the second half of pregnancy , who were infected with genital mycoplasmas and who gave written informed consent , were r and omly assigned to receive capsules of identical appearance containing erythromycin estolate , clindamycin hydrochloride , or a placebo for 6 weeks . Levels of serum glutamic oxalacetic transaminase ( SGOT ) were determined before and during treatment by a fluorometric method . All pretreatment levels of SGOT were normal ( < 41 units ) . Participants who received erythromycin estolate had significantly more abnormally elevated levels of SGOT ( 16/161 , 9.9 % ) than did those who received clindamycin ( 4/168 , 2.4 % , P < 0.01 ) or those who received placebo ( 3/165 , 1.8 % , P < 0.01 ) . Elevated levels of SGOT ranged from 44 to 130 U. Serum bilirubin levels were normal . Gamma-glutamyl transpeptidase activity was abnormal in six of six participants who had abnormal levels of SGOT while receiving erythromycin estolate . There were few associated symptoms , and all levels of SGOT returned to normal after cessation of treatment . The treatment of pregnant women with erythromycin estolate may be inadvisable BACKGROUND Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus ( HIV ) infection . However , there is uncertainty about whether prophylaxis should be continued in patients whose CD4 + cell counts have increased substantially with antiviral therapy . METHODS We conducted a multicenter , double-blind , r and omized trial of treatment with azithromycin ( 1200 mg weekly ) as compared with placebo in HIV-infected patients whose CD4 + cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy . The primary end point was M. avium complex disease or bacterial pneumonia . RESULTS A total of 520 patients entered the study ; the median CD4 + cell count at entry was 230 per cubic millimeter . In 48 percent of the patients , the HIV RNA value was below the level of quantification . The median prior nadir CD4 + cell count was 23 per cubic millimeter , and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness . During follow-up over a median period of 12 months , there were no episodes of confirmed M. avium complex disease in either group ( 95 percent confidence interval for the rate of disease in each group , 0 to 1.5 episodes per 100 person-years ) . Three patients in the azithromycin group ( 1.2 percent ) and five in the placebo group ( 1.9 percent ) had bacterial pneumonia ( relative risk in the azithromycin group , 0.60 ; 95 percent confidence interval , 0.14 to 2.50 ; P=0.48 ) . Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups . Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin ( 7.4 percent ) and in 3 assigned to receive placebo ( 1.1 percent ; relative risk , 6.6 ; P=0.002 ) . CONCLUSIONS Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4 + cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy BACKGROUND There is serological and epidemiological evidence of an association between Chlamydia pneumoniae infection and coronary artery disease . Results of previous smaller studies have indicated a reduction of recurrent ischaemic events in patients with acute coronary syndrome when given macrolide antibiotics . We aim ed to assess whether short-term treatment with the macrolide antibiotic azithromycin reduces recurrent ischaemic events in patients admitted for unstable angina or myocardial infa rct ion . METHODS We assessed the effect of azithromycin in a multicentre , double-blind r and omised trial in 1439 patients with unstable angina or acute myocardial infa rct ion . Patients were r and omly allocated to receive 500 mg azithromycin on the first day after r and omisation , followed by 250 mg daily for 4 days or placebo . Patients were followed up for 6 months . The primary endpoints were death , recurrent myocardial infa rct ion , or recurrent ischaemia necessitating revascularisation . Analysis was done by intention to treat . FINDINGS Treatment with azithromycin did not result in reduction of either individual endpoints or any of the primary endpoints . Of the 716 patients in the azithromycin group , 23 ( 3 % ) died , 17 ( 2 % ) developed myocardial infa rct ion , 65 ( 9 % ) had recurrent ischaemia needing revascularisation , and 100 ( 14 % ) had one or more of these endpoints . In the placebo group ( n=723 ) the corresponding numbers of patients were 24 ( 4 % ) , 22 ( 3 % ) , 59 ( 8 % ) , and 106 ( 15 % ) , respectively ( p=0.664 , 95 % CI 0.72 - 1.24 ) . 62 ( 9 % ) of patients in the azithromycin group and 59 ( 8 % ) in the placebo group reached the secondary endpoint of ischaemia or congestive heart failure necessitating admission ( difference 0.5 % , 95 % CI 0.75 - 1.53 ; p=0.707 ) . We recorded few side-effects . INTERPRETATION Short-term treatment with azithromycin does not reduce development of recurrent events in patients with acute coronary syndrome AIM To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants . METHODS A prospect i ve , double blind , r and omised , placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants ( < 1500 g ) consecutively admitted to the neonatal unit . The infants were r and omly allocated by minimisation to receive oral erythromycin ( 12.5 mg/kg , every six hours for 14 days ) or an equivalent volume of placebo solution ( normal saline ) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life . The times taken to establish half , three quarters , and full enteral feeding after the drug treatment were compared between the two groups . Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes . RESULTS Twenty seven and 29 infants received oral erythromycin and placebo solution respectively . The times taken to establish half , three quarters , and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo ( p < 0.05 , p < 0.05 and p < 0.0001 respectively ) . There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group ( 10v 5 infants ) . None of the infants receiving oral erythromycin developed cardiac dysrhythmia , pyloric stenosis , or septicaemia caused by multiresistant organisms . CONCLUSIONS Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility . Treated infants can achieve full enteral feeding 10 days earlier , and this may result in a substantial saving on hyperalimentation . However , until the safety of erythromycin has been confirmed in preterm infants , this treatment modality should remain experimental . Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage BACKGROUND Despite the availability of various medical treatments for pityriasis rosea , a large percentage of patients fail to achieve satisfactory results . Erythromycin is reported to be effective in the treatment of pityriasis rosea . METHODS We design ed a placebo-controlled study on 184 patients with pityriasis rosea attending the outpatient dermatology department at Hazrat-e-Rasul Hospital in Tehran , Iran . Adult patients were treated with 200 mg of erythromycin 4 times daily and children were treated with 20 to 40 mg/kg daily in 4 divided doses . Controls were given a placebo ( an emollient cream ) that was not identical in appearance . Subjects were seen at follow-up visits 2 , 4 , 6 , and 8 weeks after starting treatment . RESULTS Both groups were comparable with regard to sex , age , and mean duration of disease at the time of attending the clinic . We found no significant difference between the 2 treatment groups at weeks 4 , 6 , and 8 after beginning of treatment . ( p > .05 Chi2 ) A minority of patients with upper respiratory tract infections ( URTI ) have a bacterial infection and may benefit from antibiotherapy . In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae , Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions , resolution of symptoms was significantly improved by antibiotic treatment . The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria . Detailed clinical histories were obtained and medical examinations performed in 265 patients ( 138 females , 127 males ; mean age 35 years ) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis . The presence of three pathogenic bacteria ( S. pneumoniae , H. influenzae and M. catarrhalis ) was determined in all patients by culture of nasopharyngeal secretions . Azithromycin ( 500 mg day for 3 days ; n = 133 ) or placebo ( n = 132 ) were r and omly given to all patients in a double-blind manner . Pathogenic bacteria were found in 77 patients ( 29 % ) . The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge ( p < 0.003 ) , facial pain ( p < 0.032 ) and radiologically determined maxillary sinusitis ( complete opacity , air-fluid level or mucosal thickening>10 mm ) ( p < 0.001 ) . This best predictive model had a sensitivity of 69 % and a specificity of 64 % and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis . In the group of patients with positive bacterial cultures , resolution of symptoms at Day 7 was observed in 73 % of patients treated with azithromycin and in 47 % of patients in the placebo group ( p < 0.007 ) . We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50 % to 55 % and 8 % to 15 % , respectively , of cases of acute laryngitis in adults . This finding indicates that these organisms , M catarrhalis in particular , are in some way involved in the pathogenesis of the disorder . In the present double-blind , placebo-controlled trial , the effect of erythromycin ethylsuccinate ( 0.5 g twice a day for 5 days ) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection , as well as on subjective complaints , was evaluated in 106 adults with acute laryngitis . The bacterial isolation rates at presentation were M catarrhalis 50 % , H influenzae 18 % , and Streptococcus pneumoniae 4 % . In the 99 patients who completed the study , the elimination of M catarrhalis after 1 week was better in the erythromycin group ( 25 of 30 cases ) than in the placebo group ( 6 of 19 cases ; p ≤ .00038 ) . The elimination of H influenzae was unaffected by erythromycin . Otolaryngologic examination did not reveal any significant group differences regarding laryngitis , pharyngitis , or rhinitis . Voice quality was improved after 1 week , irrespective of treatment . However , as compared to the placebo group , the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks . As acute laryngitis in adults is self-limiting , and subjective symptoms are spontaneously reduced after 1 week in most cases , antibiotic treatment does not seem warranted as a general policy . However , erythromycin may be justified in patients who are professionally dependent on voice function PURPOSE The objective of this r and omized clinical trial was to evaluate the clinical and microbiological effects of systemic administration of roxithromycin ( RXM ) as an adjunct to non-surgical periodontal therapy ( NSPT ) in the treatment of individuals with moderate to severe chronic periodontitis ( CP ) . METHODS 70 individuals ( 38 males and 32 females , aged 25 to 60 years ) with moderate to severe CP were r and omly allocated into two groups . 35 individuals were allocated to full mouth SRP+RXM while 35 individuals were allocated to SRP+ Placebo group . The clinical parameters evaluated were probing depth ( PD ) , clinical attachment level ( CAL ) , gingival index ( GI ) , plaque index ( PI ) and % bleeding on probing sites ( % BOP ) at baseline ( B/L ) , 1- , 3- and 6-month intervals while microbiologic parameters included percentage of sites positive for periodontopathic bacteria A. actinomycetemcomitans , P. gingivalis and T. forsythia at B/L , 3 and 6 months using polymerase chain reaction . RESULTs : Both groups showed improved clinical and microbiologic parameters over 6 months . RXM group showed a statistically significant reduction in mean PD and CAL gain as compared to the placebo group ( P < 0.0001 ) . There was reduction in percentage of sites positive for periodontopathic bacteria over the duration of the study in both groups and a statistically significant reduction in the number of sites positive for A. actinomycetemcomitans in RXM group ( P < 0.001 ) Otitis media with effusion ( OME ) is a common condition among children and is characterized by nonpurulent fluid in the middle ear and fluctuating conductive hearing loss . Most children will spontaneously regain normal air-filled middle ears , but a certain number will have persistent problems . In our department we will treat annually about 500 children on an outpatient basis , with the insertion of ventilating tubes in the eardrum . The reason for this study was to evaluate the effect of erythromycin , instead of inserting a ventilation tube , in children with bilateral OME of longer duration than three months ( double blind/placebo ) . The study comprises 147 children , 1 - 15 years of age , 83 boys and 64 girls , all with OME for more than three months . All the patients were c and i date s for tube insertion . In the group treated with erythromycin , 12 patients out of 69 had bilaterally air-filled middle ears after one month , as compared to 19 out of 72 in the group treated with the placebo . No difference was noted due to sex or age . The results support our indication and timing for ventilation tube insertion The feeding regimen was st and ardised for a trial of erythromycin to reduce the time to reach full feeds ( 150 ml/kg/day ) by 30 % in neonates of < or = 32 weeks gestation . No significant improvement was noted in the primary outcome ( median time : erythromycin 93.5 vs placebo 104 hours , p = 0.60 ) . However , necrotising enterocolitis > or = stage II disappeared and the time to full feeds was reduced by over 50 % in all neonates during the 18-month trial , and for more than two years after the trial , when the st and ardised feeding regimen was adopted as routine policy for feeding neonates of < or = 32 weeks ( < 28 weeks : 13 vs 4.8 days , p < 0.05 ; > 28 weeks : 8 vs 3.9 days , p < 0.05 ) . This was in contrast to an average of six cases of NEC per year with 45 % mortality during the previous five years . The benefits of st and ardised feeding schedules -- improved detection/treatment of signs/symptoms of feed intolerance -- are emphasised OBJECTIVE We assessed the effect of prenatal and peripartum antibiotics on maternal morbidity and mortality among HIV-infected and uninfected women . METHODS A multicenter trial was conducted at clinical sites in 4 Sub-Saharan African cities : Blantyre and Lilongwe , Malawi ; Dar es Salaam , Tanzania ; and Lusaka , Zambia . A total of 1558 HIV-infected and 271 uninfected pregnant women who were eligible to receive both the prenatal and peripartum antibiotic/placebo regimens were enrolled . Pregnant women were interviewed at 20 - 24 weeks of gestation and a physical examination was performed . Women were r and omized to receive either antibiotics or placebo . At the 26 - 30 week visit , participants were given antibiotics or placebo to be taken every 4 hours beginning at the onset of labor and continuing after delivery 3 times a day until a 1-week course was completed . Logistic regression and Cox proportional hazards models were used . RESULTS There were no significant differences between the antibiotic and placebo groups for medical conditions , obstetric complications , physical examination findings , puerperal sepsis , and death in either the HIV-infected or the uninfected cohort . CONCLUSION Administration of study antibiotics during pregnancy had no effect on maternal morbidity and mortality among HIV-infected and uninfected pregnant women A r and omized clinical trial was conducted to test the postulate that erythromycin treatment of pregnant mothers may prevent preterm deliveries and low birth weight ( LBW ) in India . Vaginal swabs ( for Ureaplasma urealyticum and Mycoplasma hominis cultures ) and endocervical specimens ( for Chlamydia trachomatis antigen testing ) were obtained from 437 pregnant women : 219 for the erythromycin group and 218 for the placebo group . Findings of the study showed that mean birth weight and the incidence of LBW and preterm deliveries in both groups were similar . This result is in opposition with the existing body of evidence that reports that infections in the genital tract caused by U. urealyticum and C. trachomatis may be associated with LBW and prematurity . The study therefore concludes that erythromycin treatment of pregnant women neither decreases the incidence of LBW or preterm deliveries nor will it improve birth weight of infants Abstract The aim of the present study was to assess the hypothesis that , when present in nasopharyngeal secretions , Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection . Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled . Participants were r and omly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days . The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis in their nasopharyngeal secretions was assessed . Of 265 patients enrolled , 132 received placebo and 133 azithromycin . Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients ( 29 % ) . In this predefined subgroup of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 occurred in 73 % of those treated with azithromycin compared with 47 % of those who received placebo ( P=0.007 ) . The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group . Respiratory complications requiring antibiotic treatment occurred in 19 % of patients in the placebo group and in 3 % of the azithromycin group ( P=0.025 ) . In the remaining 188 patients without Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 was similar in both groups ( 69 % in the placebo group vs. 64 % in the azithromycin group [ P=0.75 ] ) . Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis is present in nasopharyngeal secretions . This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold We assessed the prophylactic efficacy of azithromycin ( 250 mg/day ) against malaria in 276 adults in western Thail and in a r and omized , double-blind , placebo-controlled trial . After antimalarial suppressive treatment , volunteers were r and omized in a 2:1 ratio to either the azithromycin or placebo , respectively . Study medication was given for an average of 74 days . The azithromycin group ( n = 179 ) had five endpoint parasitemias ( 1 Plasmodium vivax and 4 P. falciparum ) , and the placebo group ( n = 97 ) had 28 endpoint parasitemias ( 21 P. vivax , 5 P. falciparum , and 2 mixed infections ) . Adverse events and compliance and withdrawal rates were similar in both groups . The protective efficacy ( PE ) of azithromycin was 98 % for P. vivax ( 95 % confidence interval [ CI ] = 88 - 100 % ) . There were too few cases to reliably estimate the efficacy of azithromycin for P. falciparum ( PE = 71 % , 95 % C = -14 - 94 % ) . We conclude that daily azithromycin was safe , well-tolerated , and had a high efficacy for the prevention of P. vivax malaria OBJECTIVE Along with conventional non-surgical periodontal therapy ( NSPT ) systemic antimicrobials may provide more effective treatment for chronic periodontitis by targeting tissue-invasive bacteria . The aim of this r and omized , placebo-controlled , double-masked clinical trial was to evaluate the adjunctive effects of oral clarithromycin ( CLM ) to non-surgical periodontal therapy for chronic periodontitis . METHODS 40 patients were categorized into two groups : test group - scaling and root planing ( SRP ) plus CLM ( 500 mg b.i.d . for 3 days ) and control group - SRP plus placebo . Clinical parameters were recorded at baseline and at 1 , 3 , 6 , and 9 months . They included gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) . Also microbial analysis of dental plaque was done at baseline , 3 and 9 months to estimate the levels of periodontopathic organisms using polymerase chain reaction . ANOVA , Chi-square and Bonferroni tests were used for statistical analysis . RESULTS Thirty-seven subjects completed the study and the results demonstrated that both groups displayed clinical improvements . Using a subject-based analysis , patients treated with SRP+CLM showed enhanced reductions in PD and gains in CAL ( p<0.001 ) over time , as compared to control group . Also significant reductions in periodontopathic organisms were noticed in the test group compared to control group . However , no statistically significant differences were noted for Tannerella forsythia levels between the groups during the course of the study . CONCLUSIONS The utilisation of CLM in combination with SRP improves the efficacy of NSPT in reducing PD , improving CAL and in lessening microbial loads . Hence , CLM may be beneficial in the non-surgical treatment regimen of chronic periodontitis BACKGROUND Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties . We tested the hypothesis that azithromycin would decrease the frequency of exacerbations , increase lung function , and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis . METHODS We undertook a r and omised , double-blind , placebo-controlled trial at three centres in New Zeal and . Between Feb 12 , 2008 , and Oct 15 , 2009 , we enrolled patients who were 18 years or older , had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year , and had a diagnosis of bronchiectasis defined by high-resolution CT scan . We r and omly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio , with a permuted block size of six and sequential assignment stratified by centre . Participants , research assistants , and investigators were masked to treatment allocation . The co primary endpoints were rate of event-based exacerbations in the 6-month treatment period , change in forced expiratory volume in 1 s ( FEV(1 ) ) before bronchodilation , and change in total score on St George 's respiratory question naire ( SGRQ ) . Analyses were by intention to treat . This study is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000641493 . FINDINGS 71 patients were in the azithromycin group and 70 in the placebo group . The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period ( rate ratio 0·38 , 95 % CI 0·26 - 0·54 ; p<0·0001 ) . Prebronchodilator FEV(1 ) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group , but the difference was not significant ( 0·04 L , 95 % CI -0·03 to 0·12 ; p=0·251 ) . Additionally , change in SGRQ total score did not differ between the azithromycin ( -5·17 units ) and placebo groups ( -1·92 units ; difference -3·25 , 95 % CI -7·21 to 0·72 ; p=0·108 ) . INTERPRETATION Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year . FUNDING Health Research Council of New Zeal and and Auckl and District Health Board Charitable Trust Objective To assess the prophylactic use of erythromycin in prevention of post‐abortal pelvic inflammation disease ( PID ) in first trimester abortion OBJECTIVE This study tested the hypothesis that erythromycin , a motilin agonist , reduces the incidence of early DGE after pancreaticoduodenectomy . SUMMARY BACKGROUND DATA Delayed gastric emptying ( DGE ) is a leading cause of morbidity after pancreaticoduodenectomy , occurring in up to 40 % of patients . The pathogenesis of DGE has been speculated to involve factors such as peritonitis from anastomotic leaks , ischemia to the antropyloric muscles , and gastric atony in response to resection of the duodenal pacemaker or reduction in circulating motilin levels . METHODS Between November 1990 and January 1993 , 118 patients undergoing pancreaticoduodenectomy completed this prospect i ve , r and omized , placebo-controlled trial . The patients received either 200 mg of intravenous erythromycin lactobionate every 6 hours ( n = 58 ) , or an identical volume of 0.9 % saline ( n = 60 ) from the third to tenth postoperative days . On the tenth postoperative day , a dual phase radionuclide gastric emptying study was performed . RESULTS The erythromycin and control groups were comparable regarding multiple preoperative , intraoperative , and postoperative factors . The erythromycin group had a 37 % reduction in the incidence of DGE ( 19 % vs. 30 % ) , a significantly reduced ( p < 0.05 ) need to reinsert a nasogastric tube for DGE ( 6 vs. 15 patients ) , and a significantly reduced ( p < 0.01 ) per cent retention of liquids at 30 minutes and solids at 30 , 60 , 90 , and 120 minutes . No major adverse reactions to erythromycin were observed . CONCLUSIONS Erythromycin is a safe , inexpensive drug that significantly accelerates gastric emptying after pancreaticoduodenectomy and reduces the incidence of DGE by 37 % . These data support the use of erythromycin to decrease early DGE after pancreaticoduodenectomy Abstract Introduction : Acne vulgaris is a common problem , particularly among adolescents , which is usually resistant to monotherapy . We evaluated the efficacy and safety of a combination of azelaic acid ( AA ) 5 % and erythromycin 2 % gel ( AzE ) compared with AA 20 % or erythromycin 2 % gels in facial acne vulgaris . Methods : We conducted a 12-week , multicenter , r and omized double-blind study on 147 patients with mild-to-moderate acne vulgaris . Four treatment group were determined ( placebo , erythromycin , AA and AzE ) and followed in 4-week intervals for 12 weeks , except the placebo group which was changed to routine treatment after 4 weeks . Results : The combination of AA 5 % and erythromycin 2 % gel significantly reduced the number of papules , pustules and comedones compared with placebo ( p < 0.001 ) , erythromycin 2 % ( p < 0.01 ) or AA 20 % ( p < 0.05 ) . The incidence of adverse effects observed in patients treated with AzE ( 27 % ) was less than that with erythromycin 2 % ( 54 % ) and AA 20 % ( 45 % ) . Conclusions : The combination of AA 5 % and erythromycin 2 % produced more potent therapeutic effects in comparison with erythromycin 2 % or AA 20 % alone , and with fewer side effects BACKGROUND Macrolide resistance is an increasing problem ; there is therefore debate about when to implement maintenance treatment with macrolides in patients with chronic obstructive pulmonary disease ( COPD ) . We aim ed to investigate whether patients with COPD who had received treatment for three or more exacerbations in the previous year would have a decrease in exacerbation rate when maintenance treatment with azithromycin was added to st and ard care . METHODS We did a r and omised , double-blind , placebo-controlled , single-centre trial in The Netherl and s between May 19 , 2010 , and June 18 , 2013 . Patients ( ≥18 years ) with a diagnosis of COPD who had received treatment for three or more exacerbations in the previous year were r and omly assigned , via a computer-generated r and omisation sequence with permuted block sizes of ten , to receive 500 mg azithromycin or placebo three times a week for 12 months . R and omisation was stratified by use of long-term , low-dose prednisolone ( ≤10 mg daily ) . Patients and investigators were masked to group allocation . The primary endpoint was rate of exacerbations of COPD in the year of treatment . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00985244 . FINDINGS We r and omly assigned 92 patients to the azithromycin group ( n=47 ) or the placebo group ( n=45 ) , of whom 41 ( 87 % ) versus 36 ( 80 % ) completed the study . We recorded 84 exacerbations in patients in the azithromycin group compared with 129 in those in the placebo group . The unadjusted exacerbation rate per patient per year was 1·94 ( 95 % CI 1·50 - 2·52 ) for the azithromycin group and 3·22 ( 2·62 - 3·97 ) for the placebo group . After adjustment , azithromycin result ed in a significant reduction in the exacerbation rate versus placebo ( 0·58 , 95 % CI 0·42 - 0·79 ; p=0·001 ) . Three ( 6 % ) patients in the azithromycin group reported serious adverse events compared with five ( 11 % ) in the placebo group . During follow-up , the most common adverse event was diarrhoea in the azithromycin group ( nine [ 19 % ] patients vs one [ 2 % ] in the placebo group ; p=0·015 ) . INTERPRETATION Maintenance treatment with azithromycin significantly decreased the exacerbation rate compared with placebo and should therefore be considered for use in patients with COPD who have the frequent exacerbator phenotype and are refractory to st and ard care . FUNDING SoLong Trust CONTEXT Sexually transmitted infections ( STIs ) are common in female sex workers ( FSWs ) and may enhance susceptibility to infection with human immunodeficiency virus type 1 ( HIV-1 ) . OBJECTIVE To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1 . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted between 1998 - 2002 among FSWs in an urban slum area of Nairobi , Kenya . Of 890 FSWs screened , 466 who were seronegative for HIV-1 infection were enrolled and r and omly assigned to receive azithromycin ( n = 230 ) or placebo ( n = 236 ) . Groups were well matched at baseline for sexual risk taking and STI rates . INTERVENTION Monthly oral administration of 1 g of azithromycin or identical placebo , as directly observed therapy . All participants were provided with free condoms , risk-reduction counseling , and STI case management . MAIN OUTCOME MEASURES The primary study end point was incidence of HIV-1 infection . Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , Treponema pallidum , and Haemophilus ducreyi , as well as bacterial vaginosis . Analysis of herpes simplex virus type 2 ( HSV-2 ) infection was performed post hoc . RESULTS Seventy-three percent of participants ( n = 341 ) were followed up for 2 or more years or until they reached an administrative trial end point . Incidence of HIV-1 did not differ between treatment and placebo groups ( 4 % [ 19 cases per 473 person-years of follow-up ] vs 3.2 % [ 16 cases per 495 person-years of follow-up ] rate ratio [ RR ] , 1.2 ; 95 % CI , 0.6 - 2.5 ) . Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae ( rate ratio [ RR ] , 4.9 ; 95 % CI , 1.7 - 14.3 ) or C trachomatis ( RR , 3.0 ; 95 % CI , 1.1 - 8.9 ) . There was a reduced incidence in the treatment group of infection with N gonorrhoeae ( RR , 0.46 ; 95 % CI , 0.31 - 0.68 ) , C trachomatis ( RR , 0.38 ; 95 % CI , 0.26 - 0.57 ) , and T vaginalis ( RR , 0.56 ; 95 % CI , 0.40 - 0.78 ) . The seroprevalence of HSV-2 infection at enrollment was 72.7 % , and HSV-2 infection at baseline was independently associated with HIV-1 acquisition ( RR , 6.3 ; 95 % CI , 1.5 - 27.1 ) . CONCLUSIONS Despite an association between bacterial STIs and acquisition of HIV-1 infection , the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1 . Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1 Campylobacter concisus has been associated with prolonged mild diarrhoea , but investigations regarding the efficacy of antimicrobial treatment have not been reported previously . We initiated a phase 3 , single-centre , r and omized , double-blinded , placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days , for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days . If symptoms persisted at day ten , the patient was offered cross-over study treatment of three days and another ten-day follow-up period . The primary efficacy endpoint was the clinical response , defined as time to cessation of diarrhoea ( <3 stools/day or reversal of accompanying symptoms ) . Our estimated sample size was 100 patients . We investigated a total of 10,036 diarrheic stool sample s from 7,089 adult patients . Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility , of which 559 were excluded prior to r and omization . The three main reasons for exclusion were duration of diarrhoea longer than 21 days ( n = 124 ) , previous antibiotic treatment ( n = 113 ) , and co-pathogens in stools ( n = 87 ) . Therefore , 24 patients completed the trial with either azithromycin ( n = 12 ) or placebo ( n = 12 ) . Both groups presented symptoms of mild , prolonged diarrhoea with a mean duration of 18 days ( 95 % CI : 16–19 ) . One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period . In the azithromycin group , there was a mean of seven days ( 95 % CI : 5–9 ) to clinical cure and for the placebo group it was ten days ( 95 % CI : 6–14 ) ( OR—3 ( 95 % CI : -7–1 ) . We observed no differences in all examined outcomes between azithromycin treatment and placebo . However , due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on an effect of azithromycin treatment was not obtained . Trial Registration : Clinical trials.gov identifier : NCT01531218 An association has been reported between chronic infection with Chlamydia pneumoniae and the severity of asthma , and uncontrolled observations have suggested that treatment with antibiotics active against C. pneumoniae leads to an improvement in asthma control . We studied the effect of roxithromycin in subjects with asthma and immunoglobulin G ( IgG ) antibodies to C. pneumoniae > or = 1:64 and /or IgA antibodies > or = 1:16 . A total of 232 subjects , from Australia , New Zeal and , Italy , or Argentina , were r and omized to 6 wk of treatment with roxithromycin 150 mg twice a day or placebo . At the end of 6 wk , the increase from baseline in evening peak expiratory flow ( PEF ) was 15 L/min with roxithromycin and 3 L/min with placebo ( p = 0.02 ) . With morning PEF , the increase was 14 L/min with roxithromycin and 8 L/min with placebo ( NS ) . In the Australasian population , the increase in morning PEF was 18 L/min and 4 L/min , respectively ( p = 0.04 ) . At 3 mo and 6 mo after the end of treatment , differences between the two groups were smaller and not significant . Six weeks of treatment with roxithromycin led to improvements in asthma control but the benefit was not sustained . Further studies are necessary to determine whether the lack of sustained benefit is due to failure to eradicate C. pneumoniae AIMS Since infection of endothelial or smooth muscle cells with Chlamydia pneumoniae increased expression of tissue factor and plasminogen activator inhibitor I ( PAI-1 ) , C. pneumoniae might be involved in triggering acute thrombotic events in patients with coronary artery disease . Therefore , we explored a potential relationship between IgG-seropositivity to C. pneumoniae and early thrombotic events after coronary stent placement . METHODS AND RESULTS In a prospect i ve r and omized placebo-controlled study 1010 patients with successful coronary stent placement received roxithromycin or placebo for 4 weeks after coronary stent placement , which showed no effect of roxithromycin on early thrombotic events , as expected . Venous blood sample s were collected from patients immediately before treatment . Plasma was analyzed for C. pneumoniae-specific IgG antibody levels by microimmuno-fluorescence . Thrombotic events were defined as death , non-fatal myocardial infa rct ion , or urgent target vessel reintervention within 30 days after stent placement . We found no significant difference concerning the frequency of early thrombotic events in patients positive or negative for C. pneumoniae-specific antibodies . If patients were stratified according to their antibody levels , again no significant difference in the frequency of thrombotic events was observed . CONCLUSION Our findings do not suggest a role of C. pneumoniae in the development of early complications after stent placement Objectives Stent implantation produces a systemic increase of inflammatory markers that correlates with Chlamydophila pneumoniae infection in atherosclerotic plaque . We performed a clinical intervention study to investigate the effect of antibiotic treatment on 6-month follow-up angiographic minimal luminal diameter after stenting . Methods Ninety patients were r and omly assigned to oral azithromycin or placebo in a double-blinded and r and omized fashion . Medication was initiated 2 weeks before a pre-scheduled stenting procedure and maintained 12 weeks thereafter . Angiographic outcomes were evaluated by a six-month follow-up angiography and laboratorial parameters were accessed by blood sampling 2 weeks before stenting , within the first 24 h after procedure and additional sample s after four weeks and 6 months . Results Minimal luminal diameter ( 1.76 ± 0.56 mm Vs . 1.70 ± 0.86 mm ; P = 0.7 ) , restenosis rate , diameter stenosis , late loss , and binary restenosis rates were comparable in placebo and azithromycin group in the 6 months follow-up . Serum levels of C-reactive protein presented a three fold significant increase in the control group one day after stenting but did not change in the azithromycin group ( 8.5 [ 3.0;16.4 ] Vs . 2.9 [1.7;6.6]–median [ 25;75 percentile ] P < 0.01 ) . Conclusions Azithromycin does not improve late angiographic outcomes but attenuates the elevation of C-reactive protein levels after stenting , indicating an anti-inflammatory effect Objectives : To evaluate the effectiveness of low-dose oral erythromycin to treat feeding intolerance in preterm infants . Design : This study was a prospect i ve , double-blind , r and omized , placebo-controlled trial on 60 premature infants suffering from feeding intolerance . Thirty infants were given oral erythromycin 1 mg/kg every 8 h and 30 infants were given placebo ( normal saline ) . R and omization was stratified on enrollment according to gestational age whether > 32 weeks or ⩽32 weeks . The primary end point was the length of time taken to establish full enteral feeding since enrollment . Potential adverse effects associated with erythromycin were also monitored . Groups of each corresponding stratum were compared using two-tail t-test and Mann – Whitney for continuous variables , and χ 2 and Fisher 's exact for categorical variables . Results : For infants with gestational age > 32 weeks , the erythromycin group achieved full enteral feeding earlier than placebo group ( 10.5±4.1 vs 16.3±5.7 days , respectively ; P=0.01 ) had fewer episodes of gastric residuals ( P<0.05 ) and shorter duration of parenteral nutrition ( PN ) ( P<0.05 ) . On the other h and , in infants with gestational age ⩽32 weeks , there were no significant differences between erythromycin and placebo groups regarding any of these variables . Conclusion : Low-dose enteral erythromycin is associated with better tolerance of feeding and shorter duration of PN in infants > 32 weeks gestation . A similar effect on younger preterm infants was not demonstrable Pathogenesis and optimal treatment and prevention of preterm labor remain incompletely understood . Entry of cervical/vaginal microorganisms into lower uterine tissues has been implicated in preterm labor and may be amenable to specific therapy . Fifty-eight women with less than 34 completed weeks of gestation and without other obstetric complications , who were receiving intravenous tocolytics because of uterine contractions and who had cervical alteration ( less than 5 cm dilated ) , were enrolled in a prospect i ve r and omized , double-blinded evaluation of 7 days of adjunctive therapy with enteric-coated erythromycin base ( 333 mg three times daily by mouth ) versus placebo . Microbiologic examination included cultures for Neisseria gonorrhoeae , Chlamydia trachomatis , and group B streptococcus . Fifty-eight women with singleton pregnancies ( 29 erythromycin ; 29 placebo ) completed the protocol . Among women with cervical dilatation greater than or equal to 1 cm at the beginning of treatment , mean time until delivery was 32.5 days with erythromycin and 22.4 days with placebo treatment ( p = 0.027 ) . Of the erythromycin-treated women , seven of eight were delivered at greater than or equal to 37 weeks and only three of nine placebo-treated women were delivered at greater than or equal to 37 weeks ( p = 0.035 ) . Orally administered enteric-coated erythromycin as adjunctive treatment of pregnant women in labor less than or equal to 34 weeks is well tolerated . Adjunctive erythromycin given to women treated for preterm labor less than or equal to 34 weeks is associated with prolongation of pregnancy and delivery at 37 weeks only in women with cervical dilatation at the beginning of treatment BACKGROUND Resistance to antibiotics is a major public-health problem , and studies that link antibiotic use and resistance have shown an association but not a causal effect . We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers . METHODS Volunteers were treated with azithromycin ( n=74 ) , clarithromycin ( 74 ) , or placebo ( 76 ) in a r and omised , double-blind trial . Pharyngeal swabs were obtained before and after administration of study treatment through 180 days . The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated . Analyses were done on an intent-to-treat basis . This study is registered with Clinical Trials.gov , number NCT00354952 . FINDINGS The number of dropouts ( n=20 ) was much the same in all groups until day 42 ; dropouts increased substantially at day 180 ( 105 ) . Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied , peaking at day 8 in the clarithromycin group ( mean increase 50.0 % , 95 % CI 41.7 - 58.2 ; p<0.0001 ) and at day 4 in the azithromycin group ( 53.4 % , 43.4 - 63.5 ; p<0.0001 ) . The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use , with the largest difference between the two groups at day 28 ( 17.4 % difference , 9.2 - 25.6 ; p<0.0001 ) . Use of clarithromycin , but not of azithromycin , selected for the erm(B ) gene , which confers high-level macrolide resistance . INTERPRETATION This study shows that , notwithst and ing the different outcomes of resistance selection , macrolide use is the single most important driver of the emergence of macrolide resistance in vivo . Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics Mounting evidence supports the contention that atherosclerosis is an inflammatory disease . Recently a possible role for infectious microorganisms has gathered attention . Chlamydia pneumoniae is one possible pathogen . If C. pneumoniae is a target organism , antibiotics with antichlamydial activity may be able to ameliorate plaque instability . The WIZARD trial is a secondary prevention study that is assessing the impact of a 3-month course of azithromycin compared with placebo on the progression of clinical coronary heart disease . The study will enroll 3300 patients who have had a prior myocardial infa rct ion and who have a C. pneumoniae IgG titer of > /=1:16 . The primary end point is a composite of time to either recurrent myocardial infa rct ion , death , a revascularization procedure , or hospitalization for angina . This study is the first of a series of adequately powered clinical trials that will attempt to bridge insights from pre clinical investigations to interventions applicable to patient care BACKGROUND Clinical trials have not shown a consistent benefit of treating bronchitis with antibiotics . Many physicians , however , treat acute bronchitis with antibiotics because of the possibility of Mycoplasma pneumoniae or other pathogens . The objectives of this study were to determine the effectiveness of erythromycin treatment in patients with acute bronchitis and to determine whether a newly developed rapid M pneumoniae antibody test is useful in predicting which patients will respond to therapy . METHODS We conducted a r and omized , double-blind , placebo-controlled clinical trial at three primary care centers in North Carolina . A convenience sample of 140 patients presenting with acute bronchitis were tested for M pneumoniae , 91 of whom were treated with either erythromycin 250 mg four times daily for 10 days or an identical-appearing placebo . RESULTS Patients treated with erythromycin missed an average of only 0.81 + /- 1.1 days of work compared with 2.16 + /- 3.2 days for placebo-treated patients ( P < .02 ) . There were no significant differences in cough , use of cough medicine , general feeling of well-being , or chest congestion between the erythromycin and placebo groups . Twenty-five percent of the patients tested positive for M pneumoniae . There were no differences in response to erythromycin based on whether the patient had a positive test for M pneumoniae . CONCLUSIONS Erythromycin is effective in significantly reducing lost time from work , but it is not effective in reducing cough or other symptoms in patients with acute bronchitis , regardless of the outcome of the M pneumoniae antibody test IMPORTANCE Macrolide antibiotics such as erythromycin may improve clinical outcomes in non-cystic fibrosis ( CF ) bronchiectasis , although associated risks of macrolide resistance are poorly defined . OBJECTIVE To evaluate the clinical efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12 months to patients with non-CF bronchiectasis with a history of frequent pulmonary exacerbations . DESIGN , SETTING , AND PARTICIPANTS Twelve-month , r and omized ( 1:1 ) , double-blind , placebo-controlled trial of erythromycin in currently nonsmoking , adult patients with non-CF bronchiectasis with a history of 2 or more infective exacerbations in the preceding year . This Australian study was undertaken between October 2008 and December 2011 in a university teaching hospital , with participants also recruited via respiratory physicians at other centers and from public radio advertisements . INTERVENTIONS Twice-daily erythromycin ethylsuccinate ( 400 mg ) or matching placebo . MAIN OUTCOME MEASURES The primary outcome was the annualized mean rate of protocol -defined pulmonary exacerbations ( PDPEs ) per patient . Secondary outcomes included macrolide resistance in commensal oropharyngeal streptococci and lung function . RESULTS Six-hundred seventy-nine patients were screened , 117 were r and omized ( 58 placebo , 59 erythromycin ) , and 107 ( 91.5 % ) completed the study . Erythromycin significantly reduced PDPEs both overall ( mean , 1.29 [ 95 % CI , 0.93 - 1.65 ] vs 1.97 [ 95 % CI , 1.45 - 2.48 ] per patient per year ; incidence rate ratio [ IRR ] , 0.57 [ 95 % CI , 0.42 - 0.77 ] ; P = .003 ) , and in the prespecified subgroup with baseline Pseudomonas aeruginosa airway infection ( mean difference , 1.32 [ 95 % CI , 0.19 - 2.46 ] ; P = .02 ) . Erythromycin reduced 24-hour sputum production ( median difference , 4.3 g [ interquartile range [ IQR ] , 1 to 7.8 ] , P = .01 ) and attenuated lung function decline ( mean absolute difference for change in postbronchodilator forced expiratory volume in the first second of expiration , 2.2 percent predicted [ 95 % CI , 0.1 % to 4.3 % ] ; P = .04 ) compared with placebo . Erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci ( median change , 27.7 % [ IQR , 0.04 % to 41.1 % ] vs 0.04 % [ IQR , -1.6 % to 1.5 % ] ; difference , 25.5 % [ IQR,15.0 % to 33.7 % ] ; P < .001 ) . CONCLUSION AND RELEVANCE Among patients with non-CF bronchiectasis , the 12-month use of erythromycin compared with placebo result ed in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609000578202 In a double-blind placebo-controlled trial in patients hospitalized with campylobacter infection , erythromycin lessened pain and curtailed the carriage state but otherwise did not alter the natural course of the illness , which proved to be a short-lived , self-limiting one , even in this selected group of hospitalized patients ; the majority had become asymptomatic by the time of the bacteriological diagnosis . The rarity of bacteraemia is highlighted by the study PURPOSE : Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem . Erythromycin , a safe , inexpensive drug that stimulates intestinal motilin receptors , has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery . We aim ed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer . METHODS : Between May 1998 and April 1999 , 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospect i ve , r and omized , placebo-controlled trial . One hundred thirty-four patients completed the study . Patients were excluded if they had extensive metastatic disease , were taking medications known to interact with erythromycin , or if they required an ileostomy . Patients received either 200 mg of intravenous erythromycin or placebo every six hours . Clinical endpoints were recorded and continuous endpoints are presented as mean ± st and ard deviation . RESULTS : There were no significant complications related to erythromycin . The erythromycin ( n=65 ) and placebo ( n=69 ) groups were comparable regarding demographic and operative factors . The erythromycin group had a slightly shorter length of time to passage of flatus ( 4.1 ± 1.3vs . 4.4 ± 1.1 days;P=0.03 ) . There was no significant difference between erythromycin and placebo in time to first solid food ( 5.6 ± 1.9vs . 5.4 ± 1.8 days ) , time to first bowel movement ( 5.2 ± 1.9vs . 5.4 ± 1.3 days ) , or time to discharge from hospital ( 7.5 ± 2.0vs . 7.6 ± 2.8 days ) . There was no difference in the rate of clinical ly significant nausea ( 26vs . 26 percent;P=0.99 ) , vomiting ( 17vs . 16 percent;P=0.88 ) , or nasogastric tube placement ( 9vs . 7 percent;P=0.68 ) . CONCLUSIONS : Erythromycin does not seem to alter clinical ly important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer BACKGROUND The anti-chlamydial antibiotic , azithromycin , may improve outcome in patients who survive an acute coronary syndrome . The mechanisms are , however , poorly understood . The aims of this study were to define any relationship between Chlamydia pneumoniae seropositivity and levels of specific markers of endothelial activation ( soluble cell adhesion molecules ) and more general markers of inflammation ( C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) and to assess whether azithromycin had any effect on such markers . METHODS Patients who survived an acute coronary syndrome were r and omized to receive treatment with azithromycin ( n = 72 ) or placebo ( n = 69 ) for 5 days . Before therapy , C pneumoniae IgA and IgG titers were checked , with serum levels of soluble intercellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 , soluble E-selectin ( sE-selectin ) , soluble P-selectin , high-sensitivity CRP , and IL-6 . They were rechecked 3 months later . RESULTS There were no significant correlations between C pneumoniae titers and levels of CRP , IL-6 , or soluble cell adhesion molecules . However , azithromycin treatment significantly reduced mean sICAM-1 levels ( P = .006 ) . This effect was more marked in patients with elevated titers of C pneumoniae IgA and IgG. Soluble E-selectin levels were also reduced in patients who were seropositive , but no effects were seen on other endothelial or inflammatory markers . CONCLUSIONS After an acute coronary syndrome , a 5-day course of azithromycin reduces levels of sICAM-1 , a marker of endothelial cell activation . Although these data suggest a potentially beneficial role for azithromycin , they should be interpreted with caution BACKGROUND / PURPOSE The recovery of gut function after repair of gastroschisis is frequently prolonged , and these infants are prone to complications associated with parenteral nutrition . This trial was design ed to investigate the effect of the prokinetic agent , erythromycin , on the attainment of full enteral feeding in infants after primary repair of uncomplicated gastroschisis . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was used to investigate the effect of enteral erythromycin ( 3 mg/kg/dose 4 times daily ) compared with placebo on the attainment of full enteral feeding tolerance after primary repair of uncomplicated gastroschisis . Eleven neonatal surgical units in the United Kingdom participated in the study . The primary end-point was the time taken to achieve continuous enteral feeding at 150 mL/kg/24 hours sustained for 48 hours . RESULTS Of 70 eligible infants , 62 were recruited and r and omly divided . There were 30 patients in group I ( placebo ) and 32 in group II ( erythromycin ) . The groups were comparable in terms of mean gestational age , mean birth weight , extent of evisceration , and degree of intestinal peel . There was no statistically significant difference between the 2 groups in the time taken to achieve full enteral feeding ( 27.2 v 28.7 days ; P = .75 ) . Similarly , no significant differences were found in the incidence of catheter-related sepsis , duration of parenteral nutrition , or time to discharge between the 2 groups . CONCLUSIONS Enterally administered erythromycin at a dose of 3 mg/kg 4 times daily conferred no advantage in the time taken to achieve full enteral feeding after primary repair of uncomplicated gastroschisis OBJECTIVE The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms ( AAAs ) , and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia ( Cpn ) infection and AAA expansion . METHODS Nine vascular centers were included and 259 patients were invited to participate . Ten patients declined and 2 patients had chronic kidney failure , leaving a total of 247 patients . Inclusion criteria were : AAA 35 - 49 mm and age < 80 years . Patients were r and omized to receive either azithromycin ( Azithromax , Pfizer Inc , New York , NY ) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks , or placebo in identical tablets . The ultrasound scans were performed in a st and ardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months . Cpn serology was analyzed in blood sample s taken at inclusion and 6 months later . Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence ( MIF ) . Computed tomography ( CT ) scans were done in 66 patients at inclusion and at 1 year for volume calculations . RESULTS Thirty-four patients were excluded , ie , could not be followed for 18 months , 20 in the placebo group and 16 in the active treatment group . A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis . Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients . No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan ( 0.22 cm/year , interquartile range [ IQR ] : 0.09 to 0.34 in the placebo group vs 0.22 , IQR : 0.12 to 0.36 in the treatment group , P = .85 ) . Volume calculation did not change that outcome ( 10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group , P = .61 ) . No correlation was found between serological markers for Cpn infection and the expansion rate . Patients taking statins in combination with acetylsalicylic acid ( ASA ) had significantly reduced expansion rate compared to patients who did not take statins or ASA , 0.14 cm/year vs 0.27 cm/year , P < .001 . CONCLUSION Azithromycin did not have any effect on AAA expansion . No correlation was found between serological markers for Cpn and AAA expansion , indicating no clinical relevance for Cpn testing in AAA surveillance . However , a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins Background : Recently , a significant association between Chlamydia trachomatis infection and postoperative trachomatous trichiasis ( TT ) recurrence was shown . The current study evaluated whether azithromycin treatment at the time of surgery could reduce recurrence . Methods : As part of Nepal ’s national trachoma control programme , patients received azithromycin ( 53 patients ) or placebo ( 56 patients ) at surgery . Conjunctivae were grade d for trachoma and swabbed to detect chlamydiae preoperatively and postoperatively up to 12 months . Logistic regression was performed for associations of treatment option with recurrence , infection , and active trachoma ( by eye and by patient ) . Results : TT recurrence was 28.9 % at 12 months . Recurrence was significantly lower for those with major TT at baseline in the azithromycin group at 12 months ( p = 0.03 ) ; incident recurrence was also significantly lower at 6 months ( OR , 0.056 ; 95 % CI , 0 to 0.423 ; p = 0.004 ) . There was a trend for increased recurrence among those with minor TT at baseline and for reduction of active trachoma and infection in the azithromycin group but not the placebo group . Conclusion : These data suggest that azithromycin treatment at the time of surgery may be warranted for patients with major TT . However , treatment should be investigated further for minor TT , for efficacy at subsequent time intervals and in other trachoma endemic setting OBJECTIVES The use of prophylactic antibiotics in the management of preterm premature rupture of the membranes has not been adequately studied . The purpose of this study was to evaluate the efficacy of oral erythromycin therapy in the prolongation of latency and reduction of infectious morbidity after preterm premature rupture of membranes . STUDY DESIGN In this r and omized , prospect i ve , double-blind , placebo-controlled study , 220 women at 20 to 35 weeks ' gestation were evaluated . Subjects received oral erythromycin 333 mg ( n = 106 ) or indistinguishable placebo ( n = 114 ) every 8 hours from r and omization to delivery . RESULTS Prolongation of latency was identified with erythromycin therapy ( p = 0.02 ) , particularly for those destined to have chorioamnionitis ( p = 0.003 ) and those with oligohydramnios ( p = 0.01 ) . No decrease in the incidence of maternal or neonatal infectious morbidity was seen . CONCLUSIONS Oral erythromycin delays , but does not prevent , the onset of clinical infection when administered to women with preterm premature rupture of membranes . This regimen does not decrease neonatal morbidity and mortality ABSTRACT Atherosclerosis can to a certain extent be regarded as an inflammatory disease . Also , inflammatory markers may provide information about cardiovascular risk . Whether macrolide antibiotics , especially clarithromycin , have an anti-inflammatory effect in patients with atherosclerosis is not exactly known . To study this phenomenon , a placebo-controlled , r and omized , double-blind study was performed . A total of 231 patients with documented coronary artery disease received a daily dose of either 500 mg of slow-release clarithromycin or placebo until the day of surgery . Levels of inflammatory markers ( C-reactive protein , interleukin-2 receptor [ IL-2R ] , IL-6 , IL-8 , and tumor necrosis factor alpha ) were assessed during the preoperative outpatient visit , on the day of surgery , and 8 weeks after surgery . Also , changes in the levels of inflammatory markers between visits were determined by delta calculations . Baseline patient characteristics were balanced between the two treatment groups : the average age was 66 years ( st and ard deviation [ SD ] = 9.0 ) , 79 % of the patients were male , and the average number of tablets used was 16 ( SD = 9.3 ) . The inflammatory markers of the groups as well as the delta calculations were not significantly changed . Treatment with clarithromycin did not influence the inflammatory markers in patients with atherosclerosis BACKGROUND Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis . We aim ed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease . METHODS Between Nov 12 , 2008 , and Dec 23 , 2010 , we enrolled Indigenous Australian , Maori , and Pacific Isl and children aged 1 - 8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre , double-blind , r and omised , parallel-group , placebo-controlled trial . Eligible children had had at least one pulmonary exacerbation in the previous 12 months . Children were r and omised ( 1:1 ratio , by computer-generated sequence with permuted block design , stratified by study site and exacerbation frequency [ 1 - 2 vs ≥3 episodes in the preceding 12 months ] ) to receive either azithromycin ( 30 mg/kg ) or placebo once a week for up to 24 months . Allocation concealment was achieved by double-sealed , opaque envelopes ; participants , caregivers , and study personnel were masked to assignment until after data analysis . The primary outcome was exacerbation ( respiratory episodes treated with antibiotics ) rate . Analysis of the primary endpoint was by intention to treat . At enrolment and at their final clinic visits , children had deep nasal swabs collected , which we analysed for antibiotic-resistant bacteria . This study is registered with the Australian New Zeal and Clinical Trials Registry ; ACTRN12610000383066 . FINDINGS 45 children were assigned to azithromycin and 44 to placebo . The study was stopped early for feasibility reasons on Dec 31 , 2011 , thus children received the intervention for 12 - 24 months . The mean treatment duration was 20·7 months ( SD 5·7 ) , with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group . Compared with the placebo group , children receiving azithromycin had significantly lower exacerbation rates ( incidence rate ratio 0·50 ; 95 % CI 0·35 - 0·71 ; p<0·0001 ) . However , children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria ( 19 of 41 , 46 % ) than those receiving placebo ( four of 37 , 11 % ; p=0·002 ) . The most common adverse events were non-pulmonary infections ( 71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group ) and bronchiectasis-related events ( episodes or investigations ; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group ) ; however , study drugs were well tolerated with no serious adverse events being attributed to the intervention . INTERPRETATION Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease . However , this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria , the clinical consequences of which are uncertain , and will need careful monitoring and further study . FUNDING National Health and Medical Research Council ( Australia ) and Health Research Council ( New Zeal and ) Previous studies of acute laryngitis in adults have shown high nasopharyngeal isolation rates of B. catarrhalis and H. influenzae . Phenoxymethylpenicillin had no effect on the clinical course . In the present study , 106 patients with acute laryngitis were treated with erythromycin 0.5 g x 2 V or placebo . During the first week the isolation rate of B. catarrhalis was reduced from 60 to 10 % in the erythromycin group compared to 34 to 27 % in the placebo group ( p less than 0.01 ) . The elimination of H. influenzae , isolated in 19 % at the acute visit , did not differ between the two groups . As compared to controls , erythromycin treated patients reported significantly lower scores of subjective voice disturbance after 1 week and cough after 2 weeks . Laryngological examination and voice evaluation failed to reveal any differences between the groups Abstract Introduction : COPD is characterized by bronchial neutrophilic inflammation . Clarithromycin is a macrolide antibiotic that has antibacterial and anti-inflammatory properties . Macrolide antibiotics have been shown to improve airway inflammation in diffuse pan-bronchiolitis but their role in COPD is undetermined . The aim of the study was to determine if 3 months of therapy with modified-release oral clarithromycin ( Klaricid XL ® ) 500 mg/day reduced bronchial airway inflammation in patients with moderate-to-severe stable COPD compared with placebo . Methods : A prospect i ve , double-blind controlled trial r and omized patients with moderate-to-severe stable COPD to 3 months ’ therapy with oral modified-release clarithromycin 500 mg/day or placebo . Patients underwent saline sputum induction before and after treatment with clarithromycin . The effects of clarithromycin on sputum total cell and neutrophil counts , supernatant interleukin-8 ( IL-8 ) , leukotriene B4 ( LTB4 ) , tumor necrosis factor (TNF)-α , neutrophil elastase ( NE ) , and neutrophil chemotaxis were assessed in comparison with placebo . Results : Of a total of 67 patients included in the trial , 31 were treated with clarithromycin and 36 with placebo . The groups were similar in age , body mass index , history of smoking , and spirometry . Of 60 evaluable patients , 26 and 34 completed 3 months ’ therapy with clarithromycin and placebo , respectively . Clarithromycin had no significant effect on sputum total cell count , neutrophil count , IL-8 , LTB4 , TNFα levels or neutrophil elastase . However , clarithromycin did cause a small reduction in the neutrophil differential ( p = 0.04 relative to placebo ) and neutrophil chemotaxis ( p = 0.058 relative to placebo ) . Conclusions : Oral clarithromycin 500 mg/day administered for 3 months had no significant effect on sputum neutrophil numbers or cytokine levels in patients with moderate-to-severe stable COPD . However , clarithromycin did cause a small reduction in the neutrophil differential and neutrophil chemotaxis . Further studies may be warranted to determine the clinical significance of these findings Evidence suggests that sub clinical intrauterine infections which can be indicated by elevated maternal CRP-values may cause preterm labor and that Ureaplasma urealyticum might play a role in the pathogenesis of preterm delivery . Since these organisms are sensitive to erythromycin , 43 patients with threatened preterm labor were at the time of tocolysis treated with erythromycin , or placebo in a r and omized study . Treatment with erythromycin result ed in a greater mean delay of delivery for 9 days than among the placebo-treated women . This effect is statistically significant in patients with intact membranes and cervical dilatation : in contrast to the placebo group these women achieved an increased delay of 23 days before delivering . Moreover , successful erythromycin treatment was significantly associated with the isolation of ureaplasmas from vaginal swabs . Our results emphasize that in cases with cervical dilatation , vaginal microorganisms , especially ureaplasmas , are more liely to ascend and might be involved in the initiation of preterm labor . Therefore , additional treatment with erythromycin was beneficial only in these women BACKGROUND AND OBJECTIVE Periodontitis may alter the systemic condition in patients with diabetes and hence interfere with glycemic control . The objective of this study was to determine the quantifiable changes in glycated hemoglobin ( HbA1C ) after periodontal non-surgical therapy plus azithromycin in a mixed population of patients with poorly controlled diabetes . MATERIAL S AND METHODS One hundred and five patients were r and omized to receive non-surgical therapy plus azythromycin ( AZ-Sca = 33 ) , non-surgical therapy plus placebo ( PB-Sca = 37 ) and supragingival prophylaxis plus azithromycin ( AZ-Pro = 35 ) . Glycated hemoglobin , glycemia and periodontal parameters were measured at baseline , 3 , 6 and 9 mo after treatment . RESULTS Periodontal parameters were improved in the AZ-Sca and PB-Sca groups as compared to the AZ-Pro group . A greater reduction in probing depth was observed in the AZ-Sca as compared to the PB-Sca group . Improvement in clinical attachment level was similar between AZ-Sca and PB-Sca groups . A reduction from 8.0 % to 7.2 % ( ∆0.8 % ; p < 0.05 ) in HbA1C was observed in the AZ-Sca at 9 mo as compared to the PB-Sca group in which the reduction was from 7.9 % to 7.6 % ( ∆0.3 % ) . There was no decrease in HbA1C in the AZ-Pro group over time . Mean glycemia values decreased from 195 mg/dL to 159.2 mg/dL ( ∆35.8 mg/dL ; p < 0.05 ) in the AZ-Sca group whereas a decrease from 194 mg/dL to 174.8 mg/dL ( ∆19.2 mg/dL ) in the PB-Sca group at 9 mo was observed . There were no differences between the AZ-Sca and PB-Sca groups for glycemic parameters . No improvement in glycemic values in the AZ-Pro group was observed . CONCLUSIONS A modest improvement in glycemic control was detected with a trend towards the use of non-surgical therapy plus AZ as compared to the placebo Objective To determine whether erythromycin facilitates early enteral nutrition in mechanically ventilated , critically ill patients . Design Prospect i ve , r and omized , placebo-controlled , single-blind trial . Setting General intensive care unit in a university-affiliated general hospital . Patients Forty consecutive critically ill patients receiving invasive mechanical ventilation and early nasogastric feeding . Interventions Patients were assigned r and omly to intravenous erythromycin ( 250 mg/6 hrs ; n = 20 ) or a placebo ( intravenous 5 % dextrose , 50 mL/6 hrs ; n = 20 ) for 5 days . The first erythromycin or 5 % dextrose injection was given at 8 am on the day after intubation . One hour later , a daily 18-hr enteral nutrition regimen via a 14-Fr gastric tube was started . Residual gastric volume was aspirated and measured every day at 9 am , 3 pm , 9 pm , and 3 am . Enteral nutrition was discontinued if residual gastric volume exceeded 250 mL or the patient vomited . Measurements and Main Results On the first day , residual gastric volume was smaller in the erythromycin than in the placebo group ( 3 pm , 15 ± 7 mL vs. 52 ± 14 mL , p < .05 ; 9 pm , 29 ± 15 mL vs. 100 ± 20 mL , p < .001 ; 3 am , 11 ± 4 mL vs. 54 ± 13 mL , p < .05 ) . With erythromycin , residual gastric volume at 9 pm was smaller on the second day ( 33 ± 11 mL vs. 83 ± 19 mL , p < .01 ) and residual gastric volume at 3 pm was smaller on the third day ( 39 ± 15 mL vs. 88 ± 19 mL , p < .05 ) than with placebo . On the fourth and fifth days , the differences in residual gastric volume were not significant . Enteral nutrition was discontinued before the end of the 5-day period in seven of the 20 erythromycin patients and 14 of the 20 placebo patients ( p < .001 ) . Conclusion In critically ill patients receiving invasive mechanical ventilation , erythromycin promotes gastric emptying and improves the chances of successful early enteral nutrition Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity . Erythromycin , the only drug recommended for treatment during pregnancy , is often poorly tolerated , thus preventing successful cure . We have done a prospect i ve , r and omized , double-blind , placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia . A total of 126 patients with documented cervical infection were enrolled before 24 weeks ' gestation to receive clindamycin ( 450 mg ) , erythromycin ( 333 mg ) , or placebo orally four times daily for 14 days . Partners received doxycycline , 100 mg , twice daily for 7 days . Both clindamycin and erythromycin were effective agents with cure rates of 92.7 % and 83.8 % , respectively . Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy ( 23.1 % ( 9/39 ) vs. 2.4 % ( 1/41 ) , p less than 0.02 ) whereas clindamycin was not . Patients who experienced side effects were more likely to be poorly compliant ( p less than 0.03 ) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant ( p less than 0.002 ) . Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later A pilot study of azithromycin treatment following percutaneous coronary revascularization procedures was performed to assess safety and the effect of azithromycin treatment on anti-Chlamydia pneumoniae antibody titres . Patients were r and omized to a 1 month course of azithromycin ( total dose of 8.0 g ) or placebo . Safety and compliance were assessed at 2 and 4 weeks and serological testing was performed on sample s obtained at enrolment and at 6 months post-enrolment . Azithromycin was well tolerated at this dose . No effect of treatment on antibody titres was demonstrated . These results support further clinical trials to assess the effect of azithromycin treatment on cardiovascular disease outcomes BACKGROUND / AIMS The aim of the study was to investigate the clinical and microbiological effects of azithromycin as an adjunct to the non-surgical treatment of periodontitis in adults . Azithromycin is an antibiotic which is taken up by phagocytes and is released over long periods in inflamed tissue but requires a total of only three doses of 500 mg to produce its therapeutic effect . METHOD 46 patients were treated in a double-blind placebo-controlled study with assessment s at weeks 0 , 1 , 2 , 3 , 6 , 10 and 22 . Throughout the trial measurements were made of plaque , gingival bleeding , calculus , probing pocket depths and bleeding on probing . Microbiological sampling was carried out from a selected pocket > or=6 mm at each visit . The regime employed consisted of OHI , scaling and root planing at weeks 0 , 1 and 2 with reinforcement of OHI and minimal scaling at weeks 6 , 10 and 22 . Patients were r and omly assigned to receive either azithromycin , ( A ) , or placebo capsules , ( C ) , 500 mg , 1x daily for 3 days at week 2 . 44 patients completed the study . Mean pocket depths were analysed using analysis of covariance in 3 groups with initial pocket depth values of 1 - 3 mm , 4 - 5 mm and > or=6 mm . RESULTS The results of the microbiology have been reported in a separate paper . The clinical data showed that by week 22 a lower % of pockets initially > 5 mm deep remained above that level in the 23 patients taking azithromycin ( A ) , than the 21 taking the placebo ( C ) , ( A , 5.6 % ; C , 23.3 % ) . Also at week 22 , for pockets initially 4 mm or more , the test group had fewer pockets > 3 mm deep ( A , 26.1 % ; C , 44.3 % ) , fewer failing to improve in probing depth ( A , 6.6 % ; C , 21.6 % ) and fewer continuing to bleed on probing ( A , 46.9 % ; C , 55.6 % ) when compared with the control group . Pocket depths initially 4 - 5 mm or 6 - 9 mm analysed by analysis of covariance showed lower mean pocket depths in the patients on azithromycin , at weeks 6 , 10 and 22 , ( pockets initially 4 - 5 mm , p<0.001 on all occasions , pockets initially 6 - 9 mm , p<0.001 , week 6 ; p < 0.003 , week 10 ; p<0.001 , week 22 ) . CONCLUSIONS Azithromycin may be a useful adjunct in the treatment of adult periodontitis , particularly where deep pockets are present BACKGROUND Lyme borreliosis develops in 1 - 5 % of individuals bitten by ticks , but with a diagnostic gap affecting up to 30 % of patients , a broadly applicable pharmacological prevention strategy is needed . Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in pre clinical studies . We assessed its efficacy in human beings . METHODS In this r and omised , double-blind , placebo-controlled , multicentre trial done in 28 study sites in Germany and Austria , adults were equally assigned to receive topical 10 % azithromycin or placebo twice daily for 3 consecutive days , within 72 h of a tick bite being confirmed . R and omisation numbers , which were stratified by study site , were accessed in study centres via an interactive voice-response system , by pharmacists not involved in the study . The primary outcome was the number of treatment failures , defined as erythema migrans , seroconversion , or both , in participants who were seronegative at baseline , had no further tick bites during the study , and had serology results available at 8 weeks ( intention-to-treat [ ITT ] population ) . This study is registered with EudraCT , number 2011 - 000117 - 39 . FINDINGS Between July 7 , 2011 , and Dec 3 , 2012 , 1371 participants were r and omly assigned to treatment , of whom 995 were included in the ITT population . The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached . At 8 weeks , 11 ( 2 % ) of 505 in the azithromycin group and 11 ( 2 % ) of 490 in the placebo group had treatment failure ( odds ratio 0·97 , 95 % CI 0·42 - 2·26 , p=0·47 ) . Topical azithromycin was well tolerated . Similar numbers of patients had adverse events in the two groups ( 175 [ 26 % ] of 505 vs 177 [ 26 % ] of 490 , p=0·87 ) , and most adverse events were mild . INTERPRETATION Topical azithromycin was well tolerated and had a good safety profile . Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin . Adequately powered studies assessing only erythema migrans should be considered . A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks . FUNDING Ixodes AG CONTEXT Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis . OBJECTIVE To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure . DESIGN , SETTING , AND PARTICIPANTS R and omized , placebo-controlled trial of 7747 adults with previous myocardial infa rct ion that had occurred at least 6 weeks previously ( median , 2.6 years ) and a C pneumoniae IgG titer of 1:16 or more . Patients were recruited from 271 clinical practice s in North America , Europe , Argentina , and India , from October 10 , 1997 , to July 22 , 2001 . INTERVENTION The patients received either azithromycin ( 600 mg/d for 3 days during week 1 , then 600 mg/wk during weeks 2 - 12 ; n = 3879 ) or placebo ( n = 3868 ) . MAIN OUTCOME MEASURES The primary event was the first occurrence of death from any cause , nonfatal reinfa rct ion , coronary revascularization , or hospitalization for angina . Patients were followed up until 1038 events accrued . RESULTS After a median of 14 months of follow-up , there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo ( 7 % [ 95 % confidence interval , -5 % to 17 % ] , P = .23 ) . Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfa rct ion , but these decreased over time . There were no significant risk reductions for any of the components of the primary end point including death ( 8 % ) , recurrent myocardial infa rct ion ( 7 % ) , revascularization procedures ( 5 % ) , or hospitalizations for angina ( -1 % ) . Adverse events related to study drug were reported by 13.2 % of those r and omized to receive azithromycin , predominantly a result of diarrhea , compared with 4.6 % r and omized to receive placebo , and result ed in discontinuation of drug in 1.6 % of those taking azithromycin and 0.4 % taking placebo . CONCLUSION Among stable patients with previous myocardial infa rct ion and with evidence of C pneumoniae exposure , a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease BACKGROUND & AIMS Emergency endoscopy may be difficult in upper gastrointestinal bleeding when blood obscures the visibility . Erythromycin , a motilin agonist , induces gastric emptying . We investigated whether an intravenous bolus infusion of erythromycin would improve the yield of endoscopy in these patients . METHODS Patients admitted within 12 hours after hematemesis were r and omly assigned to erythromycin ( 250 mg ) or placebo , 20 minutes before endoscopy . The primary end point was endoscopic yield , as assessed by objective and subjective scoring systems and endoscopic duration . Secondary end points were the need for a second look , endoscopy-related complications , blood units transfused , and length of hospital stay . RESULTS Fifty-one patients received erythromycin and 54 received placebo . A clear stomach was found more often in the erythromycin group ( 82 % vs. 33 % ; P < 0.001 ) . This difference remained significant in patients with cirrhosis . Erythromycin shortened the endoscopic duration ( 13.7 vs. 16.4 minutes in the placebo group ; P = 0.036 ) and reduced the need for second-look endoscopy ( 6 vs. 17 cases ; P = 0.018 ) . Length of hospital stay and blood units transfused did not significantly differ between the 2 groups . No complications were noted . CONCLUSIONS Erythromycin infusion before endoscopy in patients with recent hematemesis makes endoscopy shorter and easier , thereby reducing the need for a repeat procedure AIM : To compare the efficacy of the coadministration of ranitidine bismuth citrate plus the antibiotic clarithromycin , with ranitidine bismuth citrate alone or clarithromycin alone for the healing of duodenal ulcers , eradication of H. pylori and the reduction of ulcer recurrence . METHODS : This two‐phase , r and omized , double‐blind , placebo‐ controlled , multicentre study consisted of a 4‐week treatment phase followed by a 24‐week post‐treatment observation phase . Patients with an active duodenal ulcer were treated with either ranitidine bismuth citrate 400 mg b.d . for 4 weeks plus clarithromycin 500 mg t.d.s . for the first 2 weeks ; ranitidine bismuth citrate 400 mg b.d . for 4 weeks plus placebo t.d.s . for first 2 weeks ; placebo b.d . for 4 weeks plus clarithromycin 500 mg t.d.s . for the first 2 weeks ; or placebo b.d . for 4 weeks plus placebo t.d.s . for the first 2 weeks . RESULTS : Ulcer healing rates after 4 weeks of treatment were highest with ranitidine bismuth citrate plus clarithromycin ( 82 % ) followed by ranitidine bismuth citrate alone ( 74 % ; P = 0.373 ) , clarithromycin alone ( 73 % ; P = 0.33 ) and placebo ( 52 % ; P = 0.007 ) . Ranitidine bismuth citrate plus clarithromycin provided significantly better ulcer symptom relief compared with clarithromycin alone or placebo ( P < 0.05 ) . The coadministration of ranitidine bismuth citrate plus clarithromycin result ed in significantly higher H. pylori eradication rates 4 weeks post‐treatment ( 82 % ) than did treatment with either ranitidine bismuth citrate alone ( 0 % ; P < 0.001 ) , clarithromycin alone ( 36 % ; P = 0.008 ) or placebo ( 0 % ; P < 0.001 ) . Ulcer recurrence rates 24 weeks post‐treatment were lower following treatment with ranitidine bismuth citrate plus clarithromycin ( 21 % ) compared with ranitidine bismuth citrate alone ( 86 % ; P < 0.001 ) , clarithromycin alone ( 40 % ; P = 0.062 ) or placebo ( 88 % ; P = 0.006 ) . All treatments were well tolerated . CONCLUSIONS : The coadministration of ranitidine bismuth citrate plus clarithromycin is a simple , well‐tolerated and effective treatment for active H. pylori‐ associated duodenal ulcer disease . This treatment regimen effectively heals duodenal ulcers , provides effective symptom relief , eradicates H. pylori infection and reduces the rate of ulcer recurrence . The eradication of H. pylori infection in patients with recently healed duodenal ulcers is associated with a significant reduction in the rate of ulcer recurrence Erythromycin stearate , 1.5 g , was effective in reducing the prevalence of streptococcal bacteraemia following dental extraction when administered orally under supervision 1 h before extraction . Blood sample s were collected from adult patients for culture and erythromycin assay 1 to 2 min after the dental procedure . High dilution techniques involving the use of 1 litre bottles of broth were used to inactivate erythromycin present in blood cultures . Viridans streptococci were isolated from 6 of 40 patients receiving erythromycin ( 15 % ) compared with 18 of 42 control patients ( 43 % ) . The mean serum erythromycin concentration at the time of extraction was 3.7 mg/l for 34 patients receiving erythromycin who had negative blood cultures compared with 1.8 mg/l for the six patients given erythromycin who had viridans streptococci isolated from the blood . Both the 1.5 g erythromycin stearate and placebo oral doses were well tolerated in a double blind comparative study which included 109 adult dental patients A possible influence of Chlamydia pneumoniae seropositivity on the clinical course of peripheral arterial occlusive disease ( PAOD ) has not been investigated previously . Though roxithromycin therapy was found to inhibit progression of PAOD , the nature of this effect ( antibiotic or anti-inflammatory ) has remained elusive . The course of PAOD was prospect ively assessed in elderly men during 4 years , comparing 51 C. pneumoniae seropositive ( IgG>/=1:128 ) with 46 seronegative patients ( IgG<1:64 and IgA<1:32 ) . Twenty of the seropositive patients were treated with roxithromycin ( 400 mg daily ) for 4 weeks . Limitation of the walking distance to 200 m or less was observed in 55 % of the seropositive untreated patients as compared to 30 % of both , seronegative and macrolide-treated patients . The number of invasive revascularizations per patient was 1.7 in the seropositive untreated group as compared to 0.5 in the seronegative and the macrolide-treated group . Considering possible confounding variables , such as classical vascular risk factors , ordinal regression analyses showed a significant association of C. pneumoniae seropositivity with limitation of the walking distance ( p=0.027 ) and need for invasive revascularization ( p=0.037 ) . The effect of macrolide treatment on these outcome measures was marked ( p<0.001 and p=0.040 , respectively ) during 2.7 years but decreased in the second part of the observation period . This study provides good evidence that C. pneumoniae are involved in the progression of PAOD and that antibiotic treatment directed against C. pneumoniae is effective in inhibiting this process Azithromycin prevents malaria in animal models and early clinical trials . We determined the prophylactic efficacy of three antibiotic regimens given for 10 weeks ( azithromycin , 250 mg daily ; azithromycin , 1,000 mg weekly ; and doxycycline , 100 mg daily ) relative to that of placebo for 232 adult volunteers residing in an area of intense malaria transmission . Any confirmed parasitemia during the study was considered a prophylactic failure . Two hundred thirteen volunteers ( 92 % ) completed the study . The prophylactic efficacies were as follows : daily azithromycin , 82.7 % ( 95 % confidence interval [ CI ] , 68.5%-91.1 % ) ; weekly azithromycin , 64.2 % ( 95 % CI , 47.1%-77.1 % ) ; and daily doxycycline , 92.6 % ( 95 % CI , 79.9%-97.5 % ) . All regimens were well tolerated . We concluded that both 100 mg of doxycycline and 250 mg of azithromycin , given daily , were effective as prophylaxis for malaria in this setting . If studies with nonimmune volunteers confirm these results for semi-immune volunteers , a daily azithromycin regimen may have special utility for individuals with contraindications to treatment with doxycycline or other antimalarial agents BACKGROUND The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease . This study investigates the effects of clarithromycin versus placebo during 10years follow up . METHODS The CLARICOR trial is a r and omised , placebo-controlled trial including 4373 patients with stable coronary heart disease . The interventions were 2weeks of clarithromycin 500 mg a day versus placebo . 10year follow up was performed through Danish public registers and analysed with Cox regression . RESULTS Clarithromycin increased all-cause mortality ( hazard ratio ( HR ) : 1.10 , 95 % confidence interval ( CI ) : 1.00 - 1.21 ) and cerebrovascular disease during 10years ( HR : 1.19 , 95 % CI : 1.02 - 1.38 ) . The increased mortality and morbidity were restricted to patients not on statin at entry ( HR : 1.16 , 95 % CI : 1.04 - 1.31 , and HR : 1.25 , 95 % CI : 1.03 - 1.50 ) . The assumption of constant HR during the 10years was violated for cardiovascular death ( P=0.01 ) and cardiovascular death outside hospital ( P<0.0005 ) . Analyses of the effects over time showed that clarithromycin increased cardiovascular mortality during the first three years ( HR : 1.42 , 95 % CI : 1.09 - 1.84 ) due to increased cardiovascular mortality outside hospital in patients not on statin ( HR : 2.36 , 95 % CI : 1.60 - 3.50 ) . During the last 4years , cardiovascular death outside hospital was lower in the clarithromycin group ( HR : 0.64 , 95 % CI : 0.46 - 0.88 ) . CONCLUSION Clarithromycin increased mortality due to cardiovascular death outside hospital and cerebrovascular morbidity in patients with stable coronary heart disease who were not on statin . The increased cardiovascular mortality was years later compensated , likely through frailty attrition The pharmacokinetics of azithromycin ( Zitromax ) , Pfizer Inc. , USA ) in tonsil tissue warranted the present trial . In 110 patients eligible for tonsillectomy because of recurrent acute tonsillitis , surgery was replaced by r and omized medication with azithromycin 500 mg or placebo once per week for 6 months . Subsequently , their clinical condition and microbiology was monitored for 12 months . Acute tonsillitis developed in 40 % of the patients who received azithromycin and in 49 % of the patients in the placebo group ( P > 0.05 ) . Accordingly , 45 % of all patients developed acute tonsillitis . Resistance to azithromycin was not detected . In this trial long-term medication with azithromycin was not efficacious in recurrent acute tonsillitis . As all patients were eligible for tonsillectomy according to current criteria , it is surprising that only 45 % developed acute tonsillitis during the trial period . Therefore , the criteria for tonsillectomy in recurrent acute tonsillitis must be revised Acute respiratory tract infection ( ARTI ) is the commonest reason for which antibiotics are prescribed , despite the fact that ARTI is mostly of viral origin . The effectiveness of antibiotics in these illnesses is , at best , question able . Jordan is a developing country where bacterial infections are thought to be more common than in developed countries and initially viral illnesses are frequently superimposed by bacterial infections . The present study represents an attempt to assess whether routine antibiotic treatment of ARTI has any beneficial effect on the course of the illness . The study was conducted in northern Jordan between 1 June and December 14 , 2000 . Patients ≥ 8 y of age visiting either of 2 health centers and diagnosed by the physician with ARTI above the level of the bronchioles were assigned on an alternating basis to receive either azithromycin or placebo . Patients were assessed at their initial visit and were subsequently followed up after 3 d , 1 week and 2 weeks . A total of 185 patients were included in the study . Patients administered azithromycin or placebo did similarly in terms of the proportions improved or cured and the duration of illness . We conclude that routine use of antibiotics ( azithromycin ) in ARTI is unlikely to alter the course of the illness Previous reports have demonstrated a gastric emptying effect of erythromycin due to a motilin-like mechanism . We studied 50 patients , scheduled for daycase laparoscopy , r and omly assigned to one of two groups : Group P patients received 30 min before induction of anaesthesia , in a double-blind manner an infusion of 250 ml dextrose 5 % while patients in Group E ( n = 25 ) received 500 mg of erythromycin diluted in 250 ml dextrose 5 % . An orogastric tube was inserted to measure both gastric pH using a pHmeter and residual gastric volume ( RG V ) using the phenol red dilutional technique . Six patients were excluded for surgical reasons . More patients in Group P ( 6/22 ) than in Group E ( 0/22 ) had RGV > 25 ml and more patients in Group P ( 17/22 ) presented with a gastric pH < 2.5 than in Group E ( 5/22 ) , P < 0.05 . Since coma and respiratory depression have been reported recently after midazolam and alfentanil administration in patients having received erythromycin , recovery conditions were assessed and were found to be comparable between groups . In conclusion , the administration of iv erythromycin before outpatient laparoscopy decreased residual gastric volume and increased gastric pH without affecting recovery from general anaesthesia . RésuméDes études récentes ont démontre que l’érythromycine augmentait la vidange gastrique grâce à un effet semblable à la motiline . Nous avons étudié 50 patientes devant subir une coelioscopie diagnostique en conditions ambulatoires . Elles ont été r and omisées en 2 groupes : celles du groupe P ( n = 25 ) ont reçu 30 minutes avant l’induction de l’anesthésie générale , en double aveugle , une perfusion de 250 ml de glucose 5 % alors que celles du group E ( n = 25 ) ont reçu 500 mg d’érythromycine dilués dans 250 ml de glucosé 5 % . Une sonde orogastrique fut introduite après l’induction pour mesurer le pH gastrique à l’aide d’un pHmètre ainsi que le volume gastrique résiduel ( RGV ) en utilisant la méthode de dilution a rouge phenol . Six patientes furent exclues de l’étude pour des raisons opératoires . Nous avons trouvé plus de patientes dans le groupe P ( 6/22 ) que dans le groupe E ( 0/22 ) présentant un RGV > 25 ml . De même , il y avail plus de patientes présentant un pH < 2.5 dans le groupe P ( 17/22 ) que dans le group E ( 5/22 ) , P < 0.05 . Des cos cliniques de troubles de conscience et de dépression respiratoire ayant été rapportés dans la littérature après administration de midazolam ou d’alfentanil chez des patients qui avaient reçu de l’érythromycine , les scores de réveil ont été évalués et se sont révilés comparables dans les deux groupes . En conclusion , l’administration intraveineuse d’érythromycine avant la coelioscopie diminue le volume gastrique résiduel et augmente le pH gastrique sans altérer les conditions de réveil après anesthésie générale Efficacy of oral , prophylactic erythromycin in reducing the time to establish full enteral feeds ( 150 ml/kg/day ) was assessed in neonates < 32 weeks , ready for enteral feeds . Seventy-three consecutive neonates were r and omised to receive oral erythromycin ethyl succinate ( n = 36 ) or placebo ( n = 37 ) in a double-blind trial until full enteral feeds or 14 days of therapy were reached . A prospect ively design ed feeding regimen , including plan of action for signs of feed intolerance , was common for all enrolled neonates . The median gestational age , birth weight and postnatal age at start of feeds were 29 versus 30 weeks ( p = 0.40 ) , 1232 versus 1280 g ( p = 0.96 ) and 5 versus 5 days ( p = 0.84 ) for erythromycin and placebo group , respectively . Time to achieve full feeds was not significantly different in the two groups . ( median times : erythromycin 93.5 versus placebo 104 hours , p = 0.60 ) . Erythromycin-related side-effects did not occur In a recently published double-blind , r and omized trial conducted by our study group , clarithromycin was intravenously administered in patients with ventilator-associated pneumonia ( VAP ) and sepsis for three consecutive days [ 1 ] . An earlier resolution of VAP and a fivefold decrease of the risk for death by septic shock and multiple organ failure ( MODS ) compared with placebo were shown CONTEXT Azithromycin is recommended as therapy for cystic fibrosis ( CF ) patients with chronic Pseudomonas aeruginosa infection , but there has not been sufficient evidence to support the benefit of azithromycin in other patients with CF . OBJECTIVE To determine if azithromycin treatment improves lung function and reduces pulmonary exacerbations in pediatric CF patients uninfected with P. aeruginosa . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized , double-blind placebo-controlled trial was conducted from February 2007 to July 2009 at 40 CF care centers in the United States and Canada . Of the 324 participants screened , 260 were r and omized and received study drug . Eligibility criteria included age of 6 to 18 years , a forced expiratory volume in the first second of expiration ( FEV(1 ) ) of at least 50 % predicted , and negative respiratory tract cultures for P. aeruginosa for at least 1 year . R and omization was stratified by age of 6 to 12 years vs 13 to 18 years and by CF center . INTERVENTION The active group ( n = 131 ) received 250 mg ( weight 18 - 35.9 kg ) or 500 mg ( weight > or = 36 kg ) of azithromycin 3 days per week ( Monday , Wednesday , and Friday ) for 168 days . The placebo group ( n = 129 ) received identically packaged placebo tablets on the same schedule . MAIN OUTCOME MEASURES The primary outcome was change in FEV(1 ) . Exploratory outcomes included additional pulmonary function end points , pulmonary exacerbations , changes in weight and height , new use of antibiotics , and hospitalizations . Changes in microbiology and adverse events were monitored . RESULTS The mean ( SD ) age of participants was 10.7 ( 3.17 ) years . The mean ( SD ) FEV(1 ) at baseline and 168 days were 2.13 ( 0.85 ) L and 2.22 ( 0.86 ) L for the azithromycin group and 2.12 ( 0.85 ) L and 2.20 ( 0.88 ) L for the placebo group . The difference in the change in FEV(1 ) between the azithromycin and placebo groups was 0.02 L ( 95 % confidence interval [ CI ] , -0.05 to 0.08 ; P = .61 ) . None of the exploratory pulmonary function end points were statistically significant . Pulmonary exacerbations occurred in 21 % of the azithromycin group and 39 % of the placebo group . Participants in the azithromycin group had a 50 % reduction in exacerbations ( 95 % CI , 31%-79 % ) and an increase in body weight of 0.58 kg ( 95 % CI , 0.14 - 1.02 ) compared with placebo participants . There were no significant differences between groups in height , use of intravenous or inhaled antibiotics , or hospitalizations . Participants in the azithromycin group had no increased risk of adverse events , but had less cough ( -23 % treatment difference ; 95 % CI , -33 % to -11 % ) and less productive cough ( -11 % treatment difference ; 95 % CI , -19 % to -3 % ) compared with placebo participants . CONCLUSION In children and adolescents with CF uninfected with P. aeruginosa , treatment with azithromycin for 24 weeks did not result in improved pulmonary function . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00431964 IMPORTANCE Many preschool children develop recurrent , severe episodes of lower respiratory tract illness ( LRTI ) . Although viral infections are often present , bacteria may also contribute to illness pathogenesis . Strategies that effectively attenuate such episodes are needed . OBJECTIVE To evaluate if early administration of azithromycin , started prior to the onset of severe LRTI symptoms , in preschool children with recurrent severe LRTIs can prevent the progression of these episodes . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled , parallel-group trial conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by December 2014 . Participants were 607 children aged 12 through 71 months with histories of recurrent , severe LRTIs and minimal day-to-day impairment . INTERVENTION Participants were r and omly assigned to receive azithromycin ( 12 mg/kg/d for 5 days ; n = 307 ) or matching placebo ( n = 300 ) , started early during each predefined RTI ( child 's signs or symptoms prior to development of LRTI ) , based on individualized action plans , over a 12- through 18-month period . MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI , measured at the level of the RTI , that would in clinical practice trigger the prescription of oral corticosteroids . Presence of azithromycin-resistant organisms in oropharyngeal sample s , along with adverse events , were among the secondary outcome measures . RESULTS A total of 937 treated RTIs ( azithromycin group , 473 ; placebo group , 464 ) were experienced by 443 children ( azithromycin group , 223 ; placebo group , 220 ) , including 92 severe LRTIs ( azithromycin group , 35 ; placebo group , 57 ) . Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo ( hazard ratio , 0.64 [ 95 % CI , 0.41 - 0.98 ] , P = .04 ; absolute risk for first RTI : 0.05 for azithromycin , 0.08 for placebo ; risk difference , 0.03 [ 95 % CI , 0.00 - 0.06 ] ) . Induction of azithromycin-resistant organisms and adverse events were infrequently observed . CONCLUSIONS AND RELEVANCE Among young children with histories of recurrent severe LRTIs , the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI . More information is needed on the development of antibiotic-resistant pathogens with this strategy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01272635 Importance Guidelines recommend against antibiotic use to treat asthma attacks . A study with telithromycin reported benefit , but adverse reactions limit its use . Objective To determine whether azithromycin added to st and ard care for asthma attacks in adults results in clinical benefit . Design , Setting , and Participants The Azithromycin Against Placebo in Exacerbations of Asthma ( AZALEA ) r and omized , double-blind , placebo-controlled clinical trial , a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations , ran from September 2011 to April 2014 . Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and /or systemic corticosteroids . Interventions Azithromycin 500 mg daily or matched placebo for 3 days . Main Outcomes and Measures The primary outcome was diary card symptom score 10 days after r and omization , with a hypothesized treatment effect size of -0.3 . Secondary outcomes were diary card symptom score , quality -of-life question naires , and lung function changes , all between exacerbation and day 10 , and time to a 50 % reduction in symptom score . Results Of 4582 patients screened at 31 centers , 199 of a planned 380 were r and omized within 48 hours of presentation . The major reason for nonrecruitment was receipt of antibiotics ( 2044 [ 44.6 % ] screened patients ) . Median time from presentation to drug administration was 22 hours ( interquartile range , 14 - 28 hours ) . Exacerbation characteristics were well balanced across treatment arms and centers . The primary outcome asthma symptom scores were mean ( SD ) , 4.14 ( 1.38 ) at exacerbation and 2.09 ( 1.71 ) at 10 days for the azithromycin group and 4.18 ( 1.48 ) and 2.20 ( 1.51 ) for the placebo group , respectively . Using multilevel modeling , there was no significant difference in symptom scores between azithromycin and placebo at day 10 ( difference , -0.166 ; 95 % CI , -0.670 to 0.337 ) , nor on any day between exacerbation and day 10 . No significant between-group differences were observed in quality -of-life question naires or lung function between exacerbation and day 10 , or in time to 50 % reduction in symptom score . Conclusions and Relevance In this r and omized population , azithromycin treatment result ed in no statistically or clinical ly significant benefit . For each patient r and omized , more than 10 were excluded because they had already received antibiotics . Trial Registration clinical trials.gov Identifier : NCT01444469 BACKGROUND The r and omized placebo-controlled double-blind CLARICOR trial investigated the influence of clarithromycin versus placebo on cardiovascular events and mortality in patients with chronic coronary artery disease ( Clinical Trials.gov NCT 00121550 ) . The trial r and omized 2172 patients to 500 mg of clarithromycin daily versus 2200 patients to matching placebo for 14 days . This paper presents protocol -specified analysis of the patient-reported information regarding their compliance and non-serious adverse events during the 14 days of treatment as well as serious adverse events ( mortality and hospitalizations ) during the first 30 days after r and omization . METHODS R and omized clinical trial focusing on patient-reported information regarding their compliance and adverse events . RESULTS Of the r and omized patients , 99 % reported information regarding their compliance and adverse events . A 100 % tablet intake was reported by 90 % of the clarithromycin group and by 93.7 % of the placebo group . Of the clarithromycin patients , 39.5 % reported at least one non-serious adverse event versus 25.1 % of the placebo patients ( P < 0.001 ) . Gastrointestinal adverse reactions were reported 950 times by 697 patients ( 32.3 % ) in the clarithromycin group and 485 times by 390 patients ( 17.9 % ) in the placebo group ( P < 0.001 ) . No significant differences were seen in other non-serious or serious adverse events during the first month after inclusion . Short-term non-serious adverse events did not explain the previously reported long-term significantly increased mortality associated with clarithromycin . CONCLUSIONS Gastrointestinal adverse reactions are common during clarithromycin administration , but at least half are also seen with a placebo To cite this article : Videler WJ , Badia L , Harvey RJ , Gane S , Georgalas C , van der Meulen FW , Menger DJ , Lehtonen MT , Toppila‐Salmi SK , Vento SI , Hytönen M , Hellings PW , Kalogjera L , Lund VJ , Scadding G , Mullol J , Fokkens WJ . Lack of Efficacy of long‐term , low‐dose azithromycin in chronic rhinosinusitis : a r and omized controlled trial . Allergy 2011 ; 66 : 1457–1468 BACKGROUND Preterm , prelabour rupture of the fetal membranes ( pPROM ) is the commonest antecedent of preterm birth , and can lead to death , neonatal disease , and long-term disability . Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate , but the results were inconclusive . We did a r and omised multicentre trial to try to resolve this issue . METHODS 4826 women with pPROM were r and omly assigned 250 mg erythromycin ( n=1197 ) , 325 mg co-amoxiclav ( 250 mg amoxicillin plus 125 mg clavulanic acid ; n=1212 ) , both ( n=1192 ) , or placebo ( n=1225 ) four times daily for 10 days or until delivery . The primary outcome measure was a composite of neonatal death , chronic lung disease , or major cerebral abnormality on ultrasonography before discharge from hospital . Analysis was by intention to treat . FINDINGS Two women were lost to follow-up , and there were 15 protocol violations . Among all 2415 infants born to women allocated erythromycin only or placebo , fewer had the primary composite outcome in the erythromycin group ( 151 of 1190 [ 12.7 % ] vs 186 of 1225 [ 15.2 % ] , p=0.08 ) than in the placebo group . Among the 2260 singletons in this comparison , significantly fewer had the composite primary outcome in the erythromycin group ( 125 of 1111 [ 11.2 % ] vs 166 of 1149 [ 14.4 % ] , p=0.02 ) . Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only . Use of erythromycin was also associated with prolongation of pregnancy , reductions in neonatal treatment with surfactant , decreases in oxygen dependence at 28 days of age and older , fewer major cerebral abnormalities on ultrasonography before discharge , and fewer positive blood cultures . Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy , they were also associated with a significantly higher rate of neonatal necrotising enterocolitis . INTERPRETATION Erythromycin for women with pPROM is associated with a range of health benefits for the neonate , and thus a probable reduction in childhood disability . However , co-amoxiclav can not be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis . A follow-up study of childhood development and disability after pPROM is planned BACKGROUND AND OBJECTIVE Systemic macrolide antibiotic administration has been shown to result in the elimination or reduction cyclosporine A-induced gingival overgrowth . Roxithromycin ( ROX ) is known to have anti-inflammatory , immunomodulatory and tissue reparative effects . This study was to evaluate the effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth and interleukin (IL)-1β , transforming growth factor (TGF)-β1 and vascular endothelial growth factor ( VEGF ) levels in gingival crevicular fluid of renal transplant patients . MATERIAL AND METHODS Thirty-one patients with clinical ly significant overgrowth and 16 periodontally healthy subjects were included in this r and omized , double-blind , placebo-controlled , parallel-arm study . Patients received scaling and root planing ( SRP ) at baseline and r and omized to take either ROX or placebo for 5 d. The clinical parameters , including plaque index , papillary bleeding index , probing depth and gingival overgrowth scores , were recorded . The amounts of IL-1β , TGF-β1 and VEGF in gingival crevicular fluid were detected by ELISA . Periodontal parameters as well as gingival crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk post-therapy . RESULTS Following SRP plus ROX and SRP plus placebo therapy , significant improvements in clinical periodontal parameters of both study groups were observed ( p < 0.025 ) . In the ROX group , adjunctive ROX therapy result ed in a greater gingival overgrowth scores reduction compared with those in the placebo group at 4 wk ( p < 0.017 ) . Initial amounts of IL-1β , TGF-β1 and VEGF for both the ROX and placebo groups were significantly higher than those for healthy subjects ( p < 0.017 ) , with no statistical difference between the two study groups . At 1 and 4 wk post-therapy , significant decreases in the amounts of IL-1β , TGF-β1 and VEGF were observed in both study groups when compared with baseline ( p < 0.025 ) , but there was no difference in the levels of IL-1β and VEGF between the two study groups . The amount of decrease in TGF-β1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment ( p < 0.017 ) . CONCLUSION Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-β1 levels in patients with severe gingival overgrowth . The reduction of gingival crevicular fluid TGF-β1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth ABSTRACT One recent , double-blind , r and omized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia ( VAP ) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions ( MODS ) . The present study focused on the effect of clarithromycin on markers of inflammation in these patients . Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment . The concentrations of circulating markers were measured . Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation . The ratio of serum interleukin-10 ( IL-10 ) to serum tumor necrosis factor alpha ( TNF-α ) was decreased in the clarithromycin group compared with the results in the placebo group . Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group . On the same day , the expression of CD86 was increased and the ratio of soluble CD40 lig and ( sCD40L ) to CD86 in serum was unchanged . The release of TNF-α , IL-6 , and soluble triggering receptor expressed on myeloid cells-1 ( sTREM-1 ) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group . The expression of TREM-1 on monocytes was also increased in the former group . These effects were pronounced in patients with septic shock and MODS . These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis ; this was accompanied by more efficient antigen presentation and increased apoptosis . These effects render new perspectives for the immunotherapy of sepsis Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus , group B streptococcus ( GBS ) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa . Asymptomatic bacterial colonization is an intermediate step towards sepsis . We conducted a phase III , double-blind , placebo-controlled r and omized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus , GBS or S. pneumoniae in the newborn at day 6 postpartum . Study participants were recruited in a health facility in western Gambia . They were followed for 8 weeks and sample s were collected during the first 4 weeks . Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies , including 13 stillbirths . Sixteen babies died during the follow-up period . No maternal deaths were observed . No serious adverse events related to the intervention were reported . According to the intent-to-treat analysis , prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm ( 28.3 % versus 65.1 % prevalence ratio 0.43 ; 95 % CI 0.36–0.52 , p < 0.001 ) . At the same time-point , prevalence of any bacteria in the mother was also lower in the azithromycin group ( nasopharynx , 9.3 % versus 40.0 % , p < 0.001 ; breast milk , 7.9 % versus 21.6 % , p < 0.001 ; and the vaginal tract , 13.2 % versus 24.2 % , p < 0.001 ) . Differences between arms lasted for at least 4 weeks . Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis . Trial registration Clinical Trials.gov Identifier NCT01800942 Abstract Background : High levels of antibodies to oral anaerobic bacteria have been found in the serum and synovial fluid of patients with rheumatoid arthritis ( RA ) . Macrolide antibiotics are active against oral anaerobic bacteria . The aim of this trial was to evaluate the efficacy of roxithromycin in patients with RA who had not responded to disease-modifying antirheumatic drugs . Methods : This was a 6-month , r and omized , double-blind , placebo-controlled trial . We treated 100 patients with active RA with either once-daily oral roxithromycin 300 mg or daily oral placebo for 6 months . The primary efficacy variable was the percentage of patients who had a 20 % improvement according to the American College of Rheumatology ( ACR ) criteria ( an ACR20 response ) at 6 months . Secondary outcome measures were 50 % improvement and 70 % improvement according to ACR criteria ( an ACR50 response and an ACR70 response , respectively ) . Results : A significantly greater percentage of patients treated with roxithromycin 300 mg met the ACR 20 % improvement criteria ( ie , achieved an ACR20 response ) at 6 months compared with patients who received placebo ( 60 % vs 34 % ; P = 0.009 ) . Greater percentages of patients treated with roxithromycin 300 mg also achieved ACR50 responses ( 38 % vs 12 % ; P = 0.003 ) and ACR70 responses ( 18 % vs 2 % ; P = 0.008 ) compared with patients who received placebo . Roxithromycin was well tolerated , with an overall safety profile similar to that of placebo . Conclusion : In patients with active RA , treatment with roxithromycin significantly improved the signs and symptoms of RA |
11,188 | 18,425,922 | AUTHORS ' CONCLUSIONS Evidence from RCTs of moderate quality suggest that psychotherapy is useful for treating depressive states in advanced cancer patients .
However , no evidence supports the effectiveness of psychotherapy for patients with clinical ly diagnosed depression | BACKGROUND The most common psychiatric diagnosis among cancer patients is depression ; this diagnosis is even more common among patients with advanced cancer .
Psychotherapy is a patient-preferred and promising strategy for treating depression among cancer patients .
Several systematic review s have investigated the effectiveness of psychological treatment for depression among cancer patients .
However , the findings are conflicting , and no review has focused on depression among patients with incurable cancer .
OBJECTIVES To investigate the effects of psychotherapy for treating depression among patients with advanced cancer by conducting a systematic review of r and omized controlled trials ( RCTs ) . | Although r and omised trials are important for evidence -based medicine , little is known about their overall characteristics . We assessed the epidemiology and reporting of method ological details for all 519 PubMed -indexed r and omised trials published in December , 2000 ( 383 [ 74 % ] parallel-group , 116 [ 22 % ] crossover ) . 482 ( 93 % ) were published in specialty journals . A median of 80 participants ( 10th-90th percentile 25 - 369 ) were recruited for parallel-group trials . 309 ( 60 % ) were blinded . Power calculation , primary outcomes , r and om sequence generation , allocation concealment , and h and ling of attrition were each adequately described in less than half of publications . The small sample sizes are worrying , and poor reporting of method ological characteristics will prevent reliable quality assessment of many published trials The purpose of this study was to examine the effect of three Therapeutic Touch treatments on the well-being of 20 persons with terminal cancer in palliative care . Participants in the experimental group ( n = 10 ) received three noncontact Therapeutic Touch treatments , the duration of which varied between 15 to 20 minutes . Participants in the control group ( n = 10 ) participated in three rest periods . Well-being was measured at preintervention time and immediately postintervention time using the Well-Being Scale , a visual analogue scale measuring pain , nausea , depression , anxiety , shortness of breath , activity , appetite , relaxation , and inner peace . The results of the study support the hypothesis that three noncontact Therapeutic Touch treatments increase sensation of well-being in persons with terminal cancer Research suggests that patients with cancer , particularly in the palliative care setting , are increasingly using aromatherapy and massage . There is good evidence that these therapies may be helpful for anxiety reduction for short periods , but few studies have looked at the longer term effects . This study was design ed to compare the effects of four-week courses of aromatherapy massage and massage alone on physical and psychological symptoms in patients with advanced cancer . Forty-two patients were r and omly allocated to receive weekly massages with lavender essential oil and an inert carrier oil ( aromatherapy group ) , an inert carrier oil only ( massage group ) or no intervention . Outcome measures included a Visual Analogue Scale ( VAS ) of pain intensity , the Verran and Snyder-Halpern ( VSH ) sleep scale , the Hospital Anxiety and Depression ( HAD ) scale and the Rotterdam Symptom Checklist ( RSCL ) . We were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control , anxiety or quality of life . However , sleep scores improved significantly in both the massage and the combined massage ( aromatherapy and massage ) groups . There were also statistically significant reductions in depression scores in the massage group . In this study of patients with advanced cancer , the addition of lavender essential oil did not appear to increase the beneficial effects of massage . Our results do suggest , however , that patients with high levels of psychological distress respond best to these therapies Much has been written about working with the dying . Few , if any , controlled studies have examined the application of principles set forth . The authors evaluate the effectiveness of working with dying cancer patients by assessing changes in quality of life , physical functioning , and survival . One‐hundred twenty men with end‐stage cancer were r and omly assigned to experimental or control groups ; the 62 experimental group patients were seen regularly by a counselor . Patients were assessed before r and om assignment and at one , three , six , nine , and 12 months on quality of life and functional status . Experimental group patients improved significantly more than the control group on quality of life within three months . Functional status and survival did not differ between groups . A sub sample of lung cancer patients provided cross‐validation of findings . Although survival was not expected to differ , it was predicted that functioning would be enhanced if quality of life improved . One interpretation is that little can be done to alter physical function and survival when intervention occurs late in the progression of a fatal disease . This in no way reduces the value of improving overall quality of life , since enhancing the quality of survival for end‐stage cancer patients is a high priority medical goal Sensory environments may potentially provide an atmosphere of calm and refreshment . This small pilot study used a r and omized controlled trial ( RCT ) design and semi-structured interviews to investigate the use of the Snoezelen multisensory environment in palliative day care . Its second aim was to explore the feasibility of the RCT design in advance of a possible larger trial . The study compared Snoezelen with a normal ' quiet room ' setting . Following screening for anxiety , 26 patients were recruited and r and omly assigned to the control of experimental group . Anxiety and depression were assessed using the Hospital Anxiety and Depression scale and quality of life assessed using the European Organisation for Research and Treatment of Cancer Core 30 question naire . A significant reduction in anxiety was seen with the experimental group ( P=0.01 ) but no changes were observed in any of the quality -of-life subscales . However , the results should be viewed with caution , as there were some differences between the groups in two of the quality -of-life subscales . Data from semi-structured interviews suggested Snoezelen might promote relaxation . It is concluded that Snoezelen is feasible for use with this patient group and recommendations are made for further research BACKGROUND Insufficient knowledge about mental illness and its treatment has been shown to constitute a major barrier to its adequate care for mental illness in the lay public ( LP ) . We therefore examined Japanese cancer patients ' ( CP ) ability to recognize depression and their preferences of its treatments . PARTICIPANTS AND METHOD One hundred lung CP and 300 LP were selected at r and om to participate in the study . Structured interviews using a vignette of a person with both cancer and depression were conducted with CP , and those using a vignette of a person with depression were carried out with LP , respectively . RESULTS Only 11 % of CP recognized the presence of depression in the vignette , while 25 % of LP did ( p<0.001 ) . There were few significant differences in the preference for st and ard psychiatric treatments between CP and LP : st and ard treatments such as antidepressants ( CP : 39 % , LP : 36 % ) were less often rated as helpful , whereas non-st and ard treatments such as physical activity ( CP : 85 % , LP : 66 % ) were most often rated as helpful . CONCLUSIONS The results indicated that cancer patients ' knowledge about mental illness and its treatment were insufficient . Psychological education may reduce patient-related barriers to seek and to utilize optimal mental health care in cancer patients PURPOSE To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation ( SCT ) and to estimate their impact on hospital length of stay ( LOS ) . PATIENTS AND METHODS In a prospect i ve inpatient study conducted from July 1994 to August 1997 , 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution . Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death , yielding a total of 1,062 psychiatric interviews performed . Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition . Univariate and multivariate linear regression analyses were used to identify variables associated with LOS . RESULTS Overall psychiatric disorder prevalence was 44.1 % ; an adjustment disorder was diagnosed in 22.7 % of patients , a mood disorder in 14.1 % , an anxiety disorder in 8.2 % , and delirium in 7.3 % . After adjusting for admission and in-hospital risk factors , diagnosis of any mood , anxiety , or adjustment disorder ( P = .022 ) , chronic myelogenous leukemia ( P = .003 ) , Karnofsky performance score less than 90 at hospital admission ( P = .025 ) , and higher regimen-related toxicity ( P < .001 ) were associated with a longer LOS . Acute lymphoblastic leukemia ( P = .009 ) , non-Hodgkin 's lymphoma ( P = .04 ) , use of peripheral-blood stem cells ( P < .001 ) , second year of study ( P < .001 ) , and third year of study ( P < .001 ) were associated with a shorter LOS . CONCLUSION Our data indicate high psychiatric morbidity and an association with longer LOS , underscoring the need for early recognition and effective treatment To examine the prevalence of depressive symptoms and its relationship with quality -of-life domains in home-care cancer patients at an advanced stage of illness , 86 patients were given psychological tests for depression ( Hospital Anxiety Depression Scale ) ( HAD ) and quality of life ( EORTC-QLQ-C30 ) 1 week after admission to the home-care program . Using a proper cut-off score on the HAD-Depression subscale , depressive symptoms were reported by 45 % of the patients . The quality of life of depressed patients was more affected than non-depressed patients in the social , emotional , cognitive , and physical domains . Significant correlations were found between depression scores and impairment in most quality -of-life areas . These findings support the importance of depression and quality -of-life evaluation in patients with advanced cancer who are followed in a home-care setting . This evaluation is needed to provide patients , their families , and caregivers with appropriate psychosocial interventions Our study belongs to the clinical trials in which the health-related quality of life ( HQL ) evaluation constitutes the primary endpoint . It was carried out with the aim of comparing the impact of three different types of psychological intervention , namely a psychopharmacological treatment alone , the same treatment plus social support carried out by volunteers ( SSV ) and a third treatment modality including “ structured psychotherapy ” ( autogenous training ) , on improving the HQL of elderly cancer patients undergoing antineoplastic therapy with symptoms of anxiety and /or depression related to their disease . The eight question naires used for HQL evaluation were generally . self-rated and multidimensional but unidimensional models were also employed . Seventy-four patients aged over 65 years with either solid tumors in different sites or hematological malignancies , generally in advanced stages ( III – IV ) , were enrolled in the study . Of these patients , 72 ( 42 men and 30 women , mean age 70.68 years , range 66–85 ) were evaluable . Our study high-lighted the usefulness of the pharmacological therapy ( alprazolam + sulpiride ) and of other specific ancillary treatments in reducing the incidence of the main HQL-related side-effects of antineoplastic therapy and the superiority of an “ integrated ” strategy , based both on psychopharmacology and psychosocial interventions , such as SSV with or without structured psychotherapy . The one-way analysis of variance carried out by us did not allow us to draw definitive conclusions about which of the two integrated treatments was to be considered the treatment of choice , as they proved to be almost equally effective This paper describes a pilot study of information giving in an oncology setting . This was achieved by r and omly allocating patients to having their consultation tape-recorded or not . The results suggest that this approach increases the retention of information in patients as well as reducing their levels of anxiety . The method is cheap and easy to use , acceptable to patients and their families , and does not inhibit the consultation process THE SPECIALTY OF PALLIATIVE CARE has experienced substantial growth and development over the past 10 years . Strong clinical palliative care programs are now firmly established in multiple setting s and venues , education in palliative care has seen strong advances with increasing penetration of palliative care content in medical school and residency curricula and continuing medical and nursing education programs , a rigorous certifying board examination for physicians has been developed , and there has been steady growth in the number of physicians who are certified in palliative medicine . Whereas we can point to these many successes in palliative care , palliative care research remains relatively underdeveloped . The evidence base for much of what we do in clinical practice remains sparse compared to more established medical specialties and important research questions in palliative care have yet to be adequately addressed or answered . Dr. Storey ’s poignant account of his difficulties in conducting high- quality rigorous research in palliative care — particularly his difficulty in conducting r and omized controlled trials — is emblematic of the problems facing palliative care research ers . If we are to conduct high- quality research in palliative care ( and indeed we must if the field is to advance ) , then our efforts must be focused equally on answering the important clinical questions of interest ( the what ) and on using the appropriate research instruments , design s , and analytic techniques ( the how ) . In this article , we identify key challenges in each of these three research areas and discuss approaches to overcoming them Two hundred fifteen r and omly accessed cancer patients who were new admissions to three collaborating cancer centers were examined for the presence of formal psychiatric disorder . Each patient was assessed in a common protocol via a psychiatric interview and st and ardized psychological tests . The American Psychiatric Association 's DSM-III diagnostic system was used in making the diagnoses . Results indicated that 47 % of the patients received a DSM-III diagnosis , with 44 % being diagnosed as manifesting a clinical syndrome and 3 % with personality disorders . Approximately 68 % of the psychiatric diagnoses consisted of adjustment disorders , with 13 % representing major affective disorders ( depression ) . The remaining diagnoses were split among organic mental disorders ( 8 % ) , personality disorders ( 7 % ) , and anxiety disorders ( 4 % ) . Approximately 85 % of those patients with a positive psychiatric condition were experiencing a disorder with depression or anxiety as the central symptom . The large majority of conditions were judged to represent highly treatable disorders 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 PURPOSE / OBJECTIVES To test the efficacy of structured symptom assessment on level and rate of change in symptom distress over time . DESIGN Prospect i ve six-month r and omized control trial . SETTING Outpatient oncology offices and clinics in California . SAMPLE 48 subjects newly diagnosed with advanced lung cancer , predominantly non-small cell . Most subjects received chemotherapy , 50 % were women , and their average age was 62 years . 190 observations were analyzed . METHODS Subjects were assigned r and omly to structured assessment or usual care . Both groups completed the Symptom Distress Scale ( SDS ) monthly . After bivariate screening of potential predictors , a multivariate regression model for level and rate of change in SDS scores was created . MAIN RESEARCH VARIABLES Symptom distress , functional status , and emotional distress . FINDINGS Fatigue was the most common severely distressing symptom . In a multivariate model , chemotherapy and systematic assessment were associated with less symptom distress over time . Higher scores in depression and more functional limitations were related to higher levels of overall distress . Weight loss had a small impact . CONCLUSIONS Systematic use of structured symptom assessment forestalled increased symptom distress over time . Chemotherapy lessened symptom distress , but the impact diminished with time . Subjects with more depression and greater functional limitations had greater symptom distress . IMPLICATION S FOR NURSING PRACTICE During the course of advanced lung cancer , systematic ongoing nursing assessment of symptoms may be the first step in enhancing interventions to decrease distress . Patients at highest risk for symptom distress are those who experience emotional distress and functional limitations |
11,189 | 19,141,093 | Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo .
In a meta- analysis restricted to short-term trials in hypercholesterolaemia , significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy . | OBJECTIVES To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary ( heterozygous familial and non-familial ) hypercholesterolaemia . | OBJECTIVE The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA ) combination tablet , relative to ezetimibe ( EZE ) and simvastatin ( SIMVA ) monotherapy , in patients with primary hypercholesterolemia . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled , factorial design study After a 6- to 8-week washout period and 4-week , single-blind , placebo run in , hypercholesterolemic patients ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides [ TG ] , < or = 350 mg/dL ) were r and omized equally to 1 of 10 daily treatments for 12 weeks : EZE/SIMVA 10/10 , 10/20 , 10/40 , or 10/80 mg ; SIMVA 10 , 20 , 40 , or 80 mg ; EZE 10 mg ; or placebo . The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [ CRP ] . RESULTS There were 1528 patients r and omized to treatment ( 792 women , 736 men ) ; mean ( SD ) age ranged from 54.9 ( 112 ) years to 56.4 ( 10.6 ) years across pooled treatment groups . The treatment groups were well balanced for baseline demographics . Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone ( P < 0.001 ) . Depending on dose , EZE/SIMVA was associated with reductions in LDL-C of -44.8 % to -602 % , non-high-density lipoprotein cholesterol of -40.5 % to -55.7 % , and TG of -22.5 % to -30.7 % ; high-density lipoprotein cholesterol increased by 5.5 % to 9.8 % . EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone ( P < 0.001 ) . More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations < 100 mg/dL ( 78.6 % vs 45.9 % ; P < 0.001 ) . EZE/SIMVA was generally well tolerated , with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal ( ULN ) ( 1 .5 % for EZE/SIMVA and 1.1 % for SIMVA ; P = NS ) or creature kinase levels > or = 10 times ULN ( 0.0 % for EZE/SIMVA and 02 % for SIMVA ; P = NS ) . CONCLUSION The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia Background —Despite the established efficacy of statins , many patients do not achieve recommended LDL cholesterol ( LDL-C ) goals . Contributing factors may be inadequate dosing , increased risk for adverse effects with high-dose monotherapy , and increased potential for intolerance and adverse effects with combinations of available agents . Methods and Results —In a double-blind study , 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides ≤350 mg/dL were r and omly assigned to receive 1 of the following for 12 weeks : ezetimibe ( 10 mg/d ) ; atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; ezetimibe ( 10 mg ) plus atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; or placebo . The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups . Ezetimibe plus atorvastatin significantly improved LDL-C , HDL cholesterol ( HDL-C ) , triglycerides , total cholesterol : HDL-C , and high-sensitivity C-reactive protein ( hs-CRP ) compared with atorvastatin alone ( P < 0.01 ) . Coadministration of ezetimibe provided a significant additional 12 % LDL-C reduction , 3 % HDL-C increase , 8 % triglyceride reduction , and 10 % hs-CRP reduction versus atorvastatin alone . Ezetimibe plus atorvastatin provided LDL-C reductions of 50 % to 60 % , triglyceride reductions of 30 % to 40 % , and HDL-C increases of 5 % to 9 % , depending on atorvastatin dose . LDL-C reductions with ezetimibe plus 10 mg atorvastatin ( 50 % ) and 80 mg atorvastatin alone ( 51 % ) were similar . Conclusions —Ezetimibe plus atorvastatin was well tolerated , with a safety profile similar to atorvastatin alone and to placebo . When coadministered with atorvastatin , ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia OBJECTIVES The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia . BACKGROUND Despite the availability of statins , many patients do not achieve lipid targets . Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals . METHODS After dietary stabilization , a 2- to 12-week washout period , and a 4-week , single-blind , placebo lead-in period , patients with baseline low-density lipoprotein cholesterol ( LDL-C ) > or = 145 mg/dl to < or = 250 mg/dl and triglycerides ( TG ) < or = 350 mg/dl were r and omized to one of the following 10 groups administered daily for 12 consecutive weeks : ezetimibe 10 mg ; simvastatin 10 , 20 , 40 , or 80 mg ; ezetimibe 10 mg plus simvastatin 10 , 20 , 40 , or 80 mg ; or placebo . The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups . RESULTS Ezetimibe plus simvastatin significantly improved LDL-C ( p < 0.01 ) , high-density lipoprotein cholesterol ( HDL-C ) ( p = 0.03 ) , and TG ( p < 0.01 ) compared with simvastatin alone . Ezetimibe plus simvastatin ( pooled doses ) provided an incremental 13.8 % LDL-C reduction , 2.4 % HDL-C increase , and 7.5 % TG reduction compared with pooled simvastatin alone . Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44 % to 57 % , TG reductions of 20 % to 28 % , and HDL-C increases of 8 % to 11 % , depending on the simvastatin dose . Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44 % LDL-C reduction . The coadministration of ezetimibe with simvastatin was well tolerated , with a safety profile similar to those of simvastatin and of placebo . CONCLUSIONS When coadministered with simvastatin , ezetimibe provided significant incremental reductions in LDL-C and TG , as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone The efficacy and safety of ezetimibe , a new cholesterol absorption inhibitor , was evaluated in this r and omized , double-blind , placebo-controlled trial of 892 patients with primary hypercholesterolemia . After > or = 2 weeks on the National Cholesterol Education Program ( NCEP ) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in , patients with low-density lipoprotein ( LDL ) cholesterol 130 to 250 mg/dl and triglycerides < or = 350 mg/dl were r and omized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks . The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point . A total of 434 men and 458 women ( ages 18 to 85 years ) received r and omized treatment ( 666 ezetimibe 10 mg , 226 placebo ) . Demographics and baseline characteristics were similar between treatment groups . Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9 % , compared with an increase of 0.4 % with placebo ( p < 0.01 ) . Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups , regardless of risk-factor status , gender , age , race , or baseline lipid profile . Ezetimibe effects on LDL cholesterol occurred early ( 2 weeks ) and persisted throughout the 12-week treatment period . Compared with placebo , ezetimibe 10 mg also significantly improved calculated LDL cholesterol , apolipoprotein B , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) cholesterol , and HDL(3 ) cholesterol ( p < 0.01 ) . Ezetimibe was well tolerated . There were no differences in laboratory or clinical safety parameters , or gastrointestinal , liver , or muscle side effects from that of placebo . Ezetimibe 10 mg/day is well tolerated , reduces LDL cholesterol approximately 17 % , and improves other key lipid parameters BACKGROUND With increased efforts to lower serum cholesterol levels , it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease , for which an etiologic relationship has been established . METHODS For an average of 12 years , 350,977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single st and ardized measurement of serum cholesterol level and other coronary heart disease risk factors ; 21,499 deaths were identified . RESULTS A strong , positive , grade d relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease . This relationship persisted over the 12-year follow-up period . No association was noted between serum cholesterol level and stroke . The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke . For the latter , a positive , grade d association with serum cholesterol level was evident . For intracranial hemorrhage , cholesterol levels less than 4.14 mmol/L ( less than 160 mg/dL ) were associated with a twofold increase in risk . A serum cholesterol level less than 4.14 mmol/L ( less than 160 mg/dL ) was also associated with a significantly increased risk of death from cancer of the liver and pancreas ; digestive diseases , particularly hepatic cirrhosis ; suicide ; and alcohol dependence syndrome . In addition , significant inverse grade d associations were found between serum cholesterol level and cancers of the lung , lymphatic , and hematopoietic systems , and chronic obstructive pulmonary disease . No significant associations were found of serum cholesterol level with death from colon cancer , with accidental deaths , or with homicides . Overall , the inverse association between serum cholesterol level and most cancers weakened with increasing follow-up but did not disappear . The association between cholesterol level and death due to cancer of the lung and liver , chronic obstructive pulmonary disease , cirrhosis , and suicide weakened little over follow-up . CONCLUSIONS The association of serum cholesterol with specific causes of death varies in direction , strength , gradation , and persistence . Further research on the determinants of low serum cholesterol level in population s and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease , whether serum cholesterol level and noncardiovascular disease are both consequences of other factors , or whether these associations are causal BACKGROUND Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve , but lipid-lowering studies have had conflicting results . METHODS We conducted a r and omized , double-blind trial involving 1873 patients with mild-to-moderate , asymptomatic aortic stenosis . The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily . The primary outcome was a composite of major cardiovascular events , including death from cardiovascular causes , aortic-valve replacement , nonfatal myocardial infa rct ion , hospitalization for unstable angina pectoris , heart failure , coronary-artery bypass grafting , percutaneous coronary intervention , and nonhemorrhagic stroke . Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events . RESULTS During a median follow-up of 52.2 months , the primary outcome occurred in 333 patients ( 35.3 % ) in the simvastatin-ezetimibe group and in 355 patients ( 38.2 % ) in the placebo group ( hazard ratio in the simvastatin-ezetimibe group , 0.96 ; 95 % confidence interval [ CI ] , 0.83 to 1.12 ; P=0.59 ) . Aortic-valve replacement was performed in 267 patients ( 28.3 % ) in the simvastatin-ezetimibe group and in 278 patients ( 29.9 % ) in the placebo group ( hazard ratio , 1.00 ; 95 % CI , 0.84 to 1.18 ; P=0.97 ) . Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group ( 148 patients ) than in the placebo group ( 187 patients ) ( hazard ratio , 0.78 ; 95 % CI , 0.63 to 0.97 ; P=0.02 ) , mainly because of the smaller number of patients who underwent coronary-artery bypass grafting . Cancer occurred more frequently in the simvastatin-ezetimibe group ( 105 vs. 70 , P=0.01 ) . CONCLUSIONS Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis . Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis . ( Clinical Trials.gov number , NCT00092677 . OBJECTIVE To compare the efficacy and safety of 10 mg of ezetimibe coadministered with simvastatin with the safety and efficacy of simvastatin monotherapy for patients with hypercholesterolemia . PATIENTS AND METHODS This multicenter double-blind , placebo-controlled , factorial study enrolled 887 patients with hypercholesterolemia ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides , < or = 350 mg/dL ) . Patients were r and omized to 1 of 10 treatments -- placebo , ezetimibe at 10 mg/d , simvastatin at 10 , 20 , 40 , or 80 mg/d , or simvastatin at 10 , 20 , 40 , or 80 mg/d plus ezetimibe at 10 mg/d for 12 weeks . The study began March 13 , 2001 , and ended January 8 , 2002 . The primary efficacy end point was the mean percent change in LDL-C levels from baseline to study end point ( last available postbaseline LDL-C measurement ) for the pooled ezetimibe/simvastatin group vs the pooled simvastatin monotherapy group . RESULTS Coadministration of ezetimibe/simvastatin was significantly ( P<.001 ) more effective than simvastatin alone in reducing LDL-C levels for the pooled ezetimibe/simvastatin vs pooled simvastatin analysis and at each specific dose comparison . The decrease in LDL-C levels with coadministration of ezetimibe and the lowest dose of simvastatin , 10 mg , was similar to the decrease with the maximum dose of simvastatin , 80 mg . A significantly ( P<.001 ) greater proportion of patients in the ezetimibe/simvastatin group achieved target LDL-C levels compared with those in the monotherapy group . Treatment with ezetimibe/simvastatin also led to greater reductions in total cholesterol , triglyceride , non-high-density lipoprotein cholesterol , and apolipoprotein B levels compared with simvastatin alone ; both treatments increased high-density lipoprotein cholesterol levels similarly . The safety and tolerability profiles for the ezetimibe/simvastatin and monotherapy groups were similar . CONCLUSION Through dual inhibition of cholesterol absorption and synthesis , coadministration of ezetimibe/simvastatin offers a highly efficacious and well-tolerated lipid-lowering strategy for treating patients with primary hypercholesterolemia This multicenter , r and omized , double-blind , placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia . After dietary stabilization , a 2- to 12-week washout period , and a 4-week single-blind placebo lead-in period , 548 patients with low-density lipoprotein ( LDL ) cholesterol > or = 145 mg/dl ( 3.75 mmol/L ) and < or = 250 mg/dl ( 6.47 mmol/L ) and triglycerides < or = 350 mg/dl ( 3.99 mmol/L ) were r and omized to one of the following , administered daily for 12 weeks : ezetimibe 10 mg ; lovastatin 10 , 20 , or 40 mg ; ezetimibe 10 mg plus lovastatin 10 , 20 , or 40 mg ; or placebo . The primary efficacy variable was percentage decrease in direct LDL cholesterol from baseline to end point for pooled ezetimibe plus lovastatin versus pooled lovastatin alone . Ezetimibe plus lovastatin significantly improved concentrations of LDL cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglycerides compared with lovastatin alone ( p < 0.01 ) . The coadministration of ezetimibe provided an incremental 14 % LDL cholesterol decrease , a 5 % HDL cholesterol increase , and a 10 % decrease in triglycerides compared with pooled lovastatin alone . Ezetimibe plus lovastatin provided mean LDL cholesterol decreases of 33 % to 45 % , median triglyceride decreases of 19 % to 27 % , and mean HDL cholesterol increases of 8 % to 9 % , depending on the statin dose . The coadministration of ezetimibe 10 mg plus the starting dose of lovastatin ( 10 mg ) provided comparable efficacy to high-dose lovastatin ( 40 mg ) across the lipid profile ( LDL cholesterol , HDL cholesterol , and triglycerides ) . Ezetimibe plus lovastatin was well tolerated , with a safety profile similar to both lovastatin alone and placebo . The coadministration of ezetimibe and lovastatin may offer a new treatment option in lipid management of patients with hypercholesterolemia BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p<0.0001 ) commenced other lipid treatments , predominantly statins . 5.9 % ( n=288 ) of patients on placebo and 5.2 % ( n=256 ) of those on fenofibrate had a coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit The Coronary Drug Project , conducted during 1966 to 1974 , was a r and omized , double-blind , placebo-controlled trial of 5 lipid-modifying agents in 8,341 men with previous myocardial infa rct ion . Among the 5 drug treatment regimens , only niacin significantly reduced the risk of ( 1 ) cardiovascular events during a mean follow-up of 6.2 years and ( 2 ) total mortality during 6.2 years with study treatment plus an additional 9 years of post-trial follow-up ( Figure 1 ) . Cardiovascular and total mortality outcomes in the niacin and placebo groups are presented by baseline glycemic status and by change in glycemic status from baseline to year 1 AIMS To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia . METHODS AND RESULTS After dietary stabilization , 2 - 12 week screening/washout period , and 4-week , single-blind , placebo lead-in period , 538 patients with baseline LDL-C > or = 3.8 to < or = 6.5 mmol/l and TG < or = 4.0 mmol/l were r and omized to one of eight possible treatments administered daily for 12 weeks : ezetimibe 10 mg ; pravastatin 10 , 20 , or 40 mg ; ezetimibe 10 mg plus pravastatin 10 , 20 , or 40 mg ; or placebo . The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin ( pooled doses ) compared to pravastatin alone ( pooled doses ) and ezetimibe alone . The combined use of ezetimibe and pravastatin result ed in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone ( p<0.01 ) . Coadministration therapy reduced LDL-C by 34 - 41 % , TG by 21 - 23 % , and increased HDL-C by 7.8 - 8.4 % , depending on the dose of pravastatin . The combined regimen was well tolerated , with a safety profile similar to pravastatin alone and placebo . CONCLUSIONS When coadministered with pravastatin , ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone |
11,190 | 28,333,357 | Generally , the results indicated that healthy diets rich in some nutrients such as omega-3 fatty acids , some antioxidants ( vitamin E , vitamin C , β-carotene , selenium , zinc , cryptoxanthin and lycopene ) , other vitamins ( vitamin D and folate ) and low in saturated fatty acids and trans-fatty acids were inversely associated with low semen quality parameters .
Fish , shellfish and seafood , poultry , cereals , vegetables and fruits , low-fat dairy and skimmed milk were positively associated with several sperm quality parameters .
However , diets rich in processed meat , soy foods , potatoes , full-fat dairy and total dairy products , cheese , coffee , alcohol , sugar-sweetened beverages and sweets have been detrimentally associated with the quality of semen in some studies .
As far as fecundability is concerned , a high intake of alcohol , caffeine and red meat and processed meat by males has a negative influence on the chance of pregnancy or fertilization rates in their partners .
WIDER IMPLICATION S Male adherence to a healthy diet could improve semen quality and fecundability rates . | BACKGROUND Infertility is a global public health issue , affecting 15 % of all couples of reproductive age .
Male factors , including decreased semen quality , are responsible for ~25 % of these cases .
The dietary pattern , the components of the diet and nutrients have been studied as possible determinants of sperm function and /or fertility .
OBJECTIVE AND RATIONALE Previous systematic review s have been made of the few heterogeneous low- quality r and omized clinical trials ( RCTs ) conducted in small sample s of participants and investigating the effect of specific nutrients and nutritional supplements on male infertility .
However , as yet there has been no systematic review of observational studies . | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) OBJECTIVE To study the relationship between men 's meat intake and clinical outcomes in couples undergoing infertility treatment with the use of assisted reproductive technology ( ART ) . DESIGN Prospect i ve cohort study . SETTING Fertility center . PATIENT(S ) A total of 141 men whose female partners underwent 246 ART cycles from 2007 to 2014 . INTERVENTION(S ) None . Total and specific types of meat intake were estimated from dietary question naires . MAIN OUTCOME MEASURE(S ) Fertilization , implantation , clinical pregnancy , and live-birth rates per initiated cycle . Mixed-effects models account for multiple IVF cycles per woman . RESULT ( S ) There was a positive association between poultry intake and fertilization rate , with a 13 % higher fertilization rate among men in the highest quartile of poultry intake compared with those in the lowest quartile ( 78 % vs. 65 % ) . Processed meat intake was inversely related to fertilization rate in conventional IVF cycles but not in IVF cycles using intracytoplasmic sperm injection . The adjusted fertilization rates for men in increasing quartiles of processed meat intake were 82 % , 67 % , 70 % , and 54 % in conventional IVF cycles . Men 's total meat intake , including intake of specific types of meat , was not associated with implantation , clinical pregnancy , or live-birth rates . CONCLUSION ( S ) Poultry intake was positively associated with fertilization rates , whereas processed meat intake was negatively associated with fertilization rates among couples undergoing conventional IVF . This , however , did not translate into associations with clinical pregnancy or live-birth rates Animal studies and human intervention trials have demonstrated the cancer chemopreventive properties of plant phytoestrogens , and phytoestrogen supplements are now widely available ' over-the-counter ' . However , consumption of phytoestrogen-rich diets can cause impaired fertility and reproductive tract disorders in some animals and the apparent decline in human sperm quality over recent decades may be related to increased exposure to environmental endocrine disruptors . The present study determines the effects of a short-term phytoestrogen supplement on semen quality and serum sex steroid and gonadotrophin levels in human males . Healthy volunteers took a supplement containing 40 mg of isoflavones daily for 2 months and donated blood and semen sample s monthly for 2 months before and 4 months after supplementation . Semen sample s were analysed for ejaculate volume , sperm concentration , total sperm count , motility and morphology . Blood sample s were analysed for sex hormone and gonadotrophin levels and phytoestrogen concentrations , and testicular volume was measured using an orchidometer . The phytoestrogen supplement increased plasma genistein and daidzein concentrations to approx . 1 microM and 0.5 microM respectively ; yet , there was no observable effect on endocrine measurements , testicular volume or semen parameters over the study period . This is the first study to examine the effects of a phytoestrogen supplement on reproductive health in males . We conclude that the phytoestrogen dose consumed had no effect on semen quality BACKGROUND In a prospect i ve study the effect of the behavioral risk factors of both partners on fecundability was studied . METHODS Information was collected on smoking habits , alcohol consumption , and caffeine intake ( e.g. coffee , tea , and cola consumption ) by interviewing 259 female nonmedical hospital workers , i.e. , clerical staff , cleaners , kitchen and restaurant workers , and their partners , who were planning a pregnancy . The occurrence of pregnancy was tested prospect ively during the 12 months after enrollment . RESULTS Among the participants as well as among their partners , smoking a moderate number of cigarettes ( 1 - 10/day ) was associated with higher fecundability ( i.e. , the probability of becoming pregnant each month ) than among those not smoking ( participant : OR = 1.4 ( 95 % CI , 0.9 - 2.2 ) ; partner : OR = 2.1 ( 95 % CI , 1.2 - 3.5 ) ) . The level of alcohol consumption in the female partner was not related to fecundability . However , in the male partner , there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 ( OR = 1.6 ; 95 % CI , 1.0 - 2.4 ) . Participants with a moderate caffeine intake ( 400 - 700 mg/day ) showed a higher fecundability than those with a lower intake level ( ORadjusted = 2.1 ( 95 % CI , 1.2 - 3.7 ) ) . Heavy caffeine intake ( > 700 mg/day ) among partners was negatively related to fecundability when compared with the lowest intake level ( ORadjusted = 0.6 ( 95 % CI , 0.3 - 0.97 ) ) . CONCLUSIONS This study does not support the hypothesis that moderate cigarette smoking , caffeine intake , and alcohol consumption have an adverse influence on fecundability OBJECTIVE To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility . Prospect i ve study . SETTING S Infertility clinic at a tertiary care academic institution . PATIENT(S ) Ninety-two infertile men with normal female partners . Sixteen fertile donors served as the control group . INTERVENTION(S ) St and ard semen analysis and assessment of levels of seminal oxidative stress . Assisted reproductive techniques in 33 of the 92 patients ( IUI [ n = 19 ] , IVF [ n = 10 ] , and intracytoplasmic sperm injection [ n = 4 ] ) . MAIN OUTCOME MEASURE(S ) Sperm DNA damage by sperm chromatin structure assay . Results were expressed as DNA fragmentation index . RESULT ( S ) Patients were classified as having either idiopathic ( n = 23 ) or male factor infertility ( n = 69 ) . Patients with idiopathic and male factor infertility had significantly higher DNA fragmentation index and oxidative stress compared with the case of fertile donors . A clinical pregnancy was achieved in 9 ( 27 % ) of 33 patients with assisted reproductive techniques . Significantly higher DNA fragmentation index and oxidative stress were found in men who failed to initiate a pregnancy after assisted reproductive techniques ( n = 24 ) , compared with the cases of those who succeeded and of the fertile donors . DNA fragmentation index was correlated positively with oxidative stress ( r = 0.27 ) , and negatively with fertilization ( r = -0.70 ) and embryo quality ( r = -0.70 ) . CONCLUSION ( S ) Sperm DNA damage is significantly increased in men with idiopathic and male factor infertility and in men who failed to initiate a pregnancy after assisted reproductive techniques . Such an increase may be related to high levels of seminal oxidative stress The fatty acid composition of sperm affects the fertilization rate . The objective was to investigate the effects of dietary fish oil ( as a source of n-3 fatty acids ) on semen quality and sperm fatty acid composition in sheep . Eight Z and i fat-tailed rams were r and omly allocated into two groups and fed either a control diet or a diet supplemented with fish oil . Both diets were isocaloric and isonitrogenous and were fed for 13 weeks , starting in the middle of the breeding season . Semen sample s were collected weekly and their characteristics evaluated by st and ard methods , whereas sample s collected at the start and end of the study were assessed ( gas chromatography ) for sperm lipid composition . Mean ( ±s.e.m . ) sperm concentrations ( 4.3 × 109 ± 1.3 × 108 v. 3.9 × 109 ± 1.3 × 108 sperm/ml and percentages of motile ( 77.25 ± 3.34 v. 60.8 ± 3.34 ) and progressively motile sperm ( 74.13 ± 1.69 v. 62.69 ± 1.69 ) were significantly higher in the fish oil group than control . Dietary fish oil increased the proportion of docosahexaenoic acid ( DHA , C22:6 n-3 ) in sperm fatty acid composition . We concluded that feeding fish oil as a source of n-3 fatty acids attenuated seasonal declines in semen quality in rams , perhaps through increased DHA in sperm OBJECTIVE To evaluate the role of the environmental estrogens polychlorinated biphenyls ( PCBs ) and phthalate esters ( PEs ) as potential environmental hazards in the deterioration of semen parameters in infertile men without an obvious etiology . DESIGN R and omized controlled study . SETTING Tertiary care referral infertility clinic and academic research center . PATIENT(S ) Twenty-one infertile men with sperm counts < 20 million/mL and /or rapid progressive motility < 25 % and /or < 30 % normal forms without evidence of an obvious etiology and 32 control men with normal semen analyses and evidence of conception . Semen and blood sample s were obtained as part of the treatment protocol . MAIN OUTCOME MEASURE(S ) Evaluation of semen parameters such as ejaculate volume , sperm count , motility , morphology , vitality , osmoregulatory capacity , sperm chromatin stability , and sperm nuclear DNA integrity . RESULT ( S ) PCBs were detected in the seminal plasma of infertile men but not in controls , and the concentration of PEs was significantly higher in infertile men compared with controls . Ejaculate volume , sperm count , progressive motility , normal morphology , and fertilizing capacity were significantly lower in infertile men compared with controls . The highest average PCB and PE concentrations were found in urban fish eaters , followed by rural fish eaters , urban vegetarians , and rural vegetarians . The total motile sperm counts in infertile men were inversely proportional to their xenoestrogen concentrations and were significantly lower than those in the respective controls . CONCLUSION ( S ) PCBs and PEs may be instrumental in the deterioration of semen quality in infertile men without an obvious etiology Ethanol is a testicular toxin and it causes fertility abnormalities with low sperm count and impaired sperm motility in men . The present study was design ed to investigate plasma testosterone level and hypothalamic pituitary gonadal ( HPG ) axis function in alcoholic men and also effect of ethanol on systemic oxidative stress . Forty six male alcohol abusers in the age group 20 - 40 years were selected . Fifty five , males in the same age group served as control . Alcohol abusers had significantly low plasma testosterone with low luteinizing hormone and follicle stimulating hormone . In addition they had significantly high thiobarbituric acid reactive substances ( TBARS ) , superoxide dismutase and glutathione S-transferase , and low glutathione , ascorbic acid , catalase , glutathione reductase and glutathione peroxidase . Moreover , serum testosterone level in alcoholics negatively correlated with duration of alcohol abuse , and TBARS . Duration dependent decreased serum testosterone level in alcohol abusers might be due to 1 ) increased oxidative stress which can damage Leydig and supporting Sertoli cells and 2 ) impaired HPG axis OBJECTIVE To assess the effect of treatment with a combination of clomiphene citrate as an antiestrogen and vitamin E as an antioxidant on the incidence of pregnancy and sperm variables in men with idiopathic oligozoospermia and infertility . DESIGN Prospect i ve , r and omized , placebo-controlled trial . SETTING The outpatient and rology clinic at a university hospital . PATIENT(S ) Sixty infertile men with idiopathic oligoasthenozoospermia . INTERVENTION(S ) Patients were r and omly assigned to two treatment groups : a group receiving the combination of clomiphene citrate ( 25 mg/day ) and vitamin E ( 400 mg/day ; n = 30 ) against a placebo group ( n = 30 ) . Treatment was maintained for 6 months . MAIN OUTCOME MEASURE(S ) Pregnancy incidence and variations in semen parameters . RESULT ( S ) A significantly higher pregnancy rate was found among the combination treatment group in comparison to the control group . The odds ratio was 3.76 and the 95 % confidence interval was 1.03 - 13.64 , with a 36.7 % pregnancy rate ( 11/30 ) in the combination treatment group compared with 13.3 % pregnancy rate ( 4/30 ) in the control group . The trial showed a significantly higher increase in sperm count and progressive sperm motility with nonsignificant changes in total sperm motility , percentage of abnormal forms and semen volume in the combination treatment group as compared to the control group . CONCLUSION ( S ) The combination of clomiphene citrate as an antiestrogen and vitamin E as an antioxidant can significantly increase the pregnancy rate and improve sperm count and progressive sperm motility in cases of idiopathic oligoasthenozoospermia OBJECTIVES To determine whether the decline in selenium intake and selenium status in men in the West of Scotl and might be a contributory factor to male subfertility . PATIENTS AND METHODS Two semen sample s were collected from patients attending a subfertility clinic and those patients with sample s showing reduced motility were invited to participate in an ethically approved double-blind clinical ly controlled trial with informed consent . Sixty-nine patients were recruited and received either placebo , selenium alone or selenium plus vitamins A , C and E daily for 3 months . A further semen sample was collected at the end of the trial . Plasma selenium status was determined at the beginning and end of the trial period , as was total sperm density and motility . RESULTS Plasma selenium concentrations were significantly ( P < 0.001 ) higher in both selenium-treated groups than in controls . No significant effect of treatment on sperm density was recorded . Sperm motility increased in both selenium-treated groups , in contrast to a slight decline in the placebo group , but the difference was not significant . However , as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment . On this basis , selenium treatment significantly ( P < 0.002 ) increased plasma selenium concentrations and sperm motility ( P = 0.023 ) but sperm density was again unaffected . Five men ( 11 % ) achieved paternity in the treatment group , in contrast to none in the placebo group . CONCLUSION This trial confirms the result of an earlier study , that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception . However , not all patients responded ; 56 % showed a positive response to treatment . The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . ) OBJECTIVE To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men . DESIGN Double-blind , placebo-controlled interventional study . SETTING Two outpatient fertility clinics and nine midwifery practice s in The Netherl and s. PARTICIPANT(S ) One hundred eight fertile and 103 subfertile men . INTERVENTION(S ) Both groups were r and omly assigned to receive one of four treatments for 26 weeks : folic acid and placebo , zinc sulfate and placebo , zinc sulfate and folic acid , and two placebos . Folic acid was given at a daily dose of 5 mg , and zinc sulfate was given at a daily dose of 66 mg . MAIN OUTCOME MEASURE(S ) Before and after treatment , st and ardized semen and blood sample s were obtained for determinations of sperm concentration , motility , and morphology according to World Health Organization guidelines ; semen morphology according to strict criteria ; and blood folate and zinc concentrations . Effects of the four interventions were evaluated separately in subfertile and fertile men . RESULT ( S ) Subfertile men demonstrated a significant 74 % increase in total normal sperm count and a minor increase of 4 % abnormal spermatozoa . A similar trend was observed in fertile men . Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men . CONCLUSION ( S ) Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men . Although the beneficial effect on fertility remains to be established , this finding opens avenues of future fertility research and treatment and may affect public health BACKGROUND AND AIM There are plausible reasons to suggest that heavy alcohol consumption reduces male as well as female fecundability , but only a few epidemiological studies have addressed this issue , and results concerning the effect of a moderate intake are equivocal . The present studies were design ed to examine the association between male and female alcohol intake at the start of the waiting time to a planned pregnancy . METHODS Two types of studies were used-a population -based study of r and omly selected women between 25 and 44 years in the different European countries from census registers and electoral rolls , and a pregnancy-based study of consecutive pregnant women ( at least 20 weeks pregnant ) recruited during prenatal care encounters . More than 4000 couples were included in each study , and 10 different regions in Europe took part in the data collection . Data were collected through personal interviews in all population -based sample s and in all but four regions of the pregnancy study . RESULTS The results showed no strong nor coherent association between alcohol intake and subfecundity . CONCLUSIONS Should any causal effect be present it is restricted to females with a high intake of alcohol within the range of normal consumption reported in European countries Effective medical treatments of infertile men with idiopathic oligoasthenoteratospermia ( OAT ) have yet to be determined . This study considered two major aims : ( i ) to measure the changes in semen parameters , omega‐3 fatty acids ( FA ) compositions and anti‐oxidant activity ; ( ii ) to determine if the administration of omega‐3 FA affect semen quality in infertile men with OAT . Two hundred thirty‐eight infertile men with idiopathic OAT were r and omised to eicosapentaenoic ( EPA ) and docosahexaenoic acids ( DHA ) , 1.84 g per day ( EPAX 5500TG ; Lysaker , Norway ) , or placebo for 32 weeks . The semen parameters were assessed according to WHO criteria , and the EPA and DHA concentrations were determined in red blood cells ( RBCs ) , seminal plasma and sperm cells at baseline and 32‐week treatment period . Of r and omised subjects , 211 ( 88.7 % ) completed the full 32‐week r and omisation period . The anti‐oxidant status of seminal plasma was also evaluated by measuring the superoxide dismutase ( SOD ) and catalase‐like activity . In the total group of participants , all EPA and DHA levels in RBC , and seminal plasma , were statistically significantly correlated with those in spermatozoa ( both P = 0.001 ) . A significant improvement of sperm cell total count ( from 38.7 ± 8.7 ′ 106 to 61.7 ± 11.2 ′ 106 , P = 0.001 ) and sperm cell concentration ( from 15.6 ± 4.1 ′ 106 per ml to 28.7 ± 4.4 ′ 106 per ml , P = 0.001 ) was observed in the omega‐3 group . A significant positive correlation was found between the EPA and DHA in seminal plasma and the semen parameters . Seminal plasma EPA and DHA concentrations were positively correlated with seminal plasma SOD‐like and catalase‐like activity ( both P = 0.001 ) . In seminal plasma , both SOD‐like and catalase‐like activity were positively correlated with sperm count , sperm motility , and sperm morphology . Oligoasthenoteratospermic men with low levels of EPA and DHA may benefit from omega‐3 FA supplementation . Further studies are warranted to shed more light on this important issue Fecundability has been defined as the ability to achieve a recognized pregnancy . Several studies on caffeine and fecundability have been conducted but have been inconclusive . This may be explained partly by lack of stratification by smoking . Furthermore , few research ers have tried to separate the effect of caffeine from different sources ( coffee , tea , cola , and chocolate ) . Clearly , the relationship between caffeine and fecundability needs further research , given the high prevalence of caffeine intake among women of childbearing age . We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception . From 1992 to 1995 , a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old , lived with a partner , and had no previous reproductive experience . At enrollment and in six cycles of follow-up , both partners filled out a question naire on different factors including smoking habits and their intake of coffee , tea , chocolate , cola beverages , and chocolate bars . In all , 1596 cycles and 423 couples were included in the analyses . The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle ( pregnant or not pregnant ) in a Cox discrete model calculating the fecundability odds-ratio ( FR ) . Compared to nonsmoking women with caffeine intake less than 300 mg/d , nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [ 95 % confidence interval ( CI ) 0.60 - 1.31 ] , whereas women with a higher caffeine intake had a FR = 0.63 ( 95 % CI 0.25 - 1.60 ) after adjusting for female body mass index and alcohol intake , diseases of the female reproductive organs , semen quality , and duration of menstrual cycle . No dose-response relationship was found among smokers . Among males , the same decline in point estimates of the FR was present . Smoking women whose only source of caffeine was coffee ( > 300 mg/d ) had a reduced fecundability odds-ratio ( FR = 0.34 ; 95 % CI 0.12 - 0.98 ) . An interaction between caffeine and smoking is biologically plausible , and the lack of effect among smokers may be due to faster metabolism of caffeine . Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake A high dietary intake of soy products ( eg , as in Japan and Singapore ) has been associated with a reduction in the incidence of breast cancer in premenopausal women . Phytoestrogens present in soybeans inhibit human breast cancer cell proliferation in vitro and breast cancer development in animal models , but no data exist on the effects of phytoestrogens on histologically normal human breasts . This study examines the effects of dietary soy supplementation on the proliferation rate of premenopausal , histologically normal breast epithelium and the expression of progesterone receptor . Women ( n = 48 ) with benign or malignant breast disease were r and omly assigned to receive their normal diet either alone or with a 60-g soy supplement ( containing 45 mg isoflavones ) taken daily for 14 d. Biopsy sample s of normal breasts were labeled with [3H]thymidine to detect the number of cells in S phase and were immunocytochemically stained for the proliferation antigen Ki67 . The phytoestrogens genistein , daidzein , equol , enterolactone , and enterodiol were measured in serum sample s obtained before and after supplementation . Serum concentrations of the isoflavones genistein and daidzein increased in the soy group at 14 d. Results showed a strong correlation between Ki67 and the thymidine labeling index ( r = 0.868 , P < or = 0.001 ) . The proliferation rate of breast lobular epithelium significantly increased after 14 d of soy supplementation when both the day of menstrual cycle and the age of patient were accounted for . Progesterone receptor expression increased significantly in the soy group . Short-term dietary soy stimulates breast proliferation ; further studies are required to determine whether this is due to estrogen agonist activity and to examine the long-term effects of soy supplementation on the pituitary gl and and breast The phospholipid and fatty acid composition of sperm was studied in 8 healthy and 16 infertile men . Infertile men r and omly formed from the patients with normal semen parameters according to WHO criterion . Therefore , all semen parameters of infertile patients were similar to the same characteristics of the semen of healthy men , except the abnormal forms . The amount of abnormal forms in infertile men was significantly higher than in healthy men . Sperm from infertile men show a drastic loss of phosphatidyl ethanolamine . At the same time , the significant increase of phosphatidyl serine in the sperm and seminal plasma of sterile patients was found . Lysophosphatidyl serine in the sperm of the infertile men was detected . Fatty acid composition of the semen of infertile men was altered . The levels of stearic and n-3 polyunsaturated fatty acids ( eicosopentaenoic and docosahexaenoic acids ) was dramatically lowered , but the values of some n-6 polyunsaturated fatty acids ( linolenic and docosatetraenoic ) acids increased . There was significant positive correlation between docosahexaenoic acid and sperm motility ( r = .82 , p < .001 ) and negative correlation between linolenic acid and spermatozoa motility ( r = -0.58 . p < .05 ) . Infertility of men with normal semen quality can originate from the disorder of sperm lipid metabolism . The drastic loss of phosphatidyl ethanolamine and n-3 polyunsaturated fatty acids with simultaneous enhancement of phosphatidyl serine and some n-6 polyunsaturated fatty acids in sperm could be an important cause of male infertility OBJECTIVE To evaluate the effects of chronic alcoholism on the male fertility hormones and quality of semen . DESIGN Non-probability purposive clinical study . SETTING Addiction treatment center and an academic research environment . PATIENT(S ) Sixty-six alcoholics free from smoking and drug abuse who consumed a minimum of 180 mL of alcohol per day ( br and y and whisky , both 40%-50 % alcohol content ) for a minimum of 5 days per week for > or = 1 year were included . Thirty nonsmoking nonalcoholics were selected as controls . INTERVENTION(S ) Before starting the addiction treatment for alcoholics , venous blood and semen sample s were collected . MAIN OUTCOME MEASURE(S ) Complete blood counts , biochemical parameters , levels of the male fertility hormones FSH , LH , T , PRL , P , and E2 in blood , and semen parameters . RESULT ( S ) In alcoholics , FSH , LH , and E2 levels were significantly increased , and T and P levels were significantly decreased . No significant change was noted in PRL levels . Semen volume , sperm count , motility , and number of morphologically normal sperm were significantly decreased . CONCLUSION ( S ) Chronic alcohol consumption has a detrimental effect on male reproductive hormones and on semen quality The objective of this study was to examine the effect of dietary n-3 polyunsaturated fatty acid ( PUFA ) supplementation of rams on semen quality and subsequent sperm function of liquid stored semen . Mature rams of proven fertility were individually housed and were blocked according to breed , body weight , and body condition score and r and omly allocated within block to one of two dietary treatments ( N = 7 per treatment ) . Rams were offered a base diet of hay and concentrate , with the concentrate enriched with either : ( 1 ) saturated palmitic acid ( CON ) or ( 2 ) high n-3 PUFA fish oil ( FO ) supplements . Both lipid supplements were added at 2 % ( wt/wt ) of the total diet as fed and both were partially rumen-protected . The animals were fed their respective diets for a total of 9 weeks and blood sample s were collected on weeks 0 ( pre-experimental ) , 4 , and 9 , relative to initial allocation of diet ( week 0 ) , for measurement of plasma concentration of fatty acids , metabolites , insulin like growth factor 1 ( IGF-1 ) and insulin . Semen was collected from each ram ( on 1 day in each week ) in weeks 4 , 5 , 7 , 8 , and 9 , and each ejaculate was assessed for volume , wave motion , and concentration of sperm , after which it was diluted in a skim milk-based extender and stored at 4 ° C . A second ejaculate was collected on weeks 4 , 7 , and 9 , centrifuged , and the sperm frozen for subsequent lipid analysis . A sample of semen from each ram was assessed at 24 , 48 , and 72 hours after collection for sperm progressive linear motion , ability to penetrate artificial mucus , and the ability to resist lipid peroxidation ( at 24 and 48 hours only ) using the thiobarbituric acid reactive substances assay . There was no effect of diet on plasma insulin concentrations or on any of the metabolites measured , however , there was a diet by week interaction for plasma IGF-1 concentration ( P < 0.05 ) . This was manifested as the FO supplemented rams having higher IGF-1 concentrations on week 9 compared with the control treatment ( P < 0.05 ) , but not at the earlier sampling date s. Compared with the pre-experimental values , supplementation with FO increased plasma concentrations of total n-3 PUFAs by 3.1-fold and decreased n-6 PUFA concentrations by 1.84-fold . Consequently , the ratio of n-6 to n-3 PUFA was decreased in the FO-supplemented rams ( P < 0.001 ) . Dietary supplementation with FO increased the concentration of eicosapentaenoic acid in sperm from week 4 to 9 by 2.7-fold ( P < 0.05 ) leading to a 1.5-fold increase in total n-3 PUFA in the same period . Ejaculates collected from rams supplemented with FO yielded a higher semen concentration ( P < 0.05 ) , however , there was no difference between diets on any of the other semen quality parameters including semen volume , wave motion , progressive linear motion , ability to penetrate artificial mucus , or ability to resist lipid peroxidation . In conclusion , dietary supplementation of rams with n-3 PUFA successfully increased the n-3 PUFA content of plasma and sperm but has limited effects on the quality of liquid stored semen Emerging literature suggests that men 's diets may affect spermatogenesis as reflected in semen quality indicators , but literature on the relation between meat intake and semen quality is limited . Our objective was to prospect ively examine the relation between meat intake and indicators of semen quality . Men in subfertile couples presenting for evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility . A total of 155 men completed a vali date d food-frequency question naire and subsequently provided 338 semen sample s over an 18-mo period from 2007 - 2012 . We used linear mixed regression models to examine the relation between meat intake and semen quality indicators ( total sperm count , sperm concentration , progressive motility , morphology , and semen volume ) while adjusting for potential confounders and accounting for within-person variability across repeat semen sample s. Among the 155 men ( median age : 36.1 y ; 83 % white , non-Hispanic ) , processed meat intake was inversely related to sperm morphology . Men in the highest quartile of processed meat intake had , on average , 1.7 percentage units ( 95 % CI : -3.3 , -0.04 ) fewer morphologically normal sperm than men in the lowest quartile of intake ( P-trend = 0.02 ) . Fish intake was related to higher sperm count and percentage of morphologically normal sperm . The adjusted mean total sperm count increased from 102 million ( 95 % CI : 80 , 131 ) in the lowest quartile to 168 million ( 95 % CI : 136 , 207 ) sperm in the highest quartile of fish intake ( P-trend = 0.005 ) . Similarly , the adjusted mean percentages of morphologically normal sperm for men in increasing quartiles of fish intake were 5.9 ( 95 % CI : 5.0 , 6.8 ) , 5.3 ( 95 % CI : 4.4 , 6.3 ) , 6.3 ( 95 % CI : 5.2 , 7.4 ) , and 7.5 ( 95 % CI : 6.5 , 8.5 ) ( P-trend = 0.01 ) . Consuming fish may have a positive impact on sperm counts and morphology , particularly when consumed instead of processed red meats |
11,191 | 28,086,992 | Discussion This systematic review aims at identifying and evaluating therapies to treat bruxism . | Background Bruxism is a sleep disorder characterized by grinding and clenching of the teeth that may be related to irreversible tooth injuries .
It is a prevalent condition occurring in up to 31 % of adults .
However , there is no definitive answer as to which of the many currently available treatments ( including drug therapy , intramuscular injections , physiotherapy , biofeedback , kinesiotherapy , use of intraoral devices , or psychological therapy ) is the best for the clinical management of the different manifestations of bruxism .
The aim of this systematic review and network meta- analysis is to answer the following question : what is the best treatment for adult bruxists ? | Abstract The present investigation is a preliminary double-blind , controlled placebo , r and omized clinical trial with a six month follow-up period . The study aim ed to assess the efficacy of type A botulinum toxin ( Botox , Allergan , Inc. Irvine , CA ) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers . Twenty patients ( ten males , ten females ; age range 25 - 45 ) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind , controlled placebo , r and omized clinical trial , with a treatment group ( ten subjects treated with botulinum toxin injections- BTX-A ) and a control group ( ten subjects treated with saline placebo injections ) . A number of objective and subjective clinical parameters ( pain at rest and during chewing ; mastication efficiency ; maximum nonassisted and assisted mouth opening , protrusive and laterotrusive movements ; functional limitation during usual jaw movements ; subjective efficacy of the treatment ; tolerance of the treatment ) were assessed at baseline time and at one week , one month , and six months follow-up appointments . Descriptive analysis showed that improvements in both objective ( range of m and ibular movements ) and subjective ( pain at rest ; pain during chewing ) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects . Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects . Differences were not significant in some cases due to the small sample size . Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers , and provided pilot data which need to be confirmed by further research using larger sample Background Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition . The two clinical manifestations of the condition ( sleep and awake bruxism ) are thought to have unrelated aetiologies but are palliated using similar techniques . The lack of a definitive treatment has prompted renewed interest in biofeedback , a behaviour change method that uses electronic detection to provide a stimulus whenever bruxism occurs . This systematic review aims to provide a comprehensive overview of the state of research into biofeedback for bruxism ; to assess the efficacy and acceptability of biofeedback therapy in management of awake bruxism and , separately , sleep bruxism in adults ; and to compare findings between the two variants . Methods A systematic review of published literature examining biofeedback as an intervention directed at controlling primary bruxism in adults . We will search electronic data bases and the grey literature using a predefined search strategy to identify r and omised and non-r and omised studies , technical reports and patents . Search es will not be restricted by language or date and will be exp and ed through contact with authors and experts , and by following up reference lists and citations . Two authors , working independently , will conduct screening of search results , study selection , data extraction and quality assessment and a third will resolve any disagreements . The primary outcomes of acceptability and effectiveness will be assessed using only r and omised studies , segregated by bruxism subtype . A meta- analysis of these data will be conducted only if pre-defined conditions for quality and heterogeneity are met , otherwise the data will be summarized in narrative form . Data from non-r and omised studies will be used to augment a narrative synthesis of the state of technical developments and any safety-related issues . PROSPERO registration number : CRD42013006880 . Discussion Biofeedback is not new , but its place in the clinical management of bruxism remains unclear . New research , and the availability of miniaturized consumer- grade devices , makes a systematic review timely to guide treatment decisions and inform future research The aim of this study was to assess the effects of sleep hygiene measures combined with relaxation techniques in the management of sleep bruxism ( SB ) in a double-blind , parallel , controlled , r and omised clinical trial design . Sixteen participants ( mean ± s.d . age = 39·9 ± 10·8 years ) were r and omly assigned to a control group ( n = 8) or to the experimental treatment group ( n = 8) . Participants belonging to the latter group were instructed to perform sleep hygiene measures and progressive muscle relaxation techniques for a 4-week period . Two polysomnographic recordings , including bilateral masseter electromyographic activity , were made : one prior to the treatment and the other after the treatment period . The number of bruxism episodes per hour , the number of burst per hour and the bruxism time index ( i.e. the percentage of total sleep time spent bruxing ) were established as outcome variables . No significant differences could be observed between the outcome measures obtained before and after the 4-week period , neither for the sleep bruxism variables nor for the sleep variables . Within the limitations of this study , it was concluded that there is no effect of sleep hygiene measures together with progressive relaxation techniques on sleep bruxism or sleep over a 4-week observation period OBJECTIVES Sleep bruxism ( SB ) frequently is associated with other sleep disorders and pain concerns . Our study assesses the efficacy of a m and ibular advancement appliance ( MAA ) for SB management in adolescents reporting snoring and headache ( HA ) . METHODS Sixteen adolescents ( mean age , 14.9±0.5 ) reporting SB , HA ( > 1d/wk ) , or snoring underwent four ambulatory polysomnographies for baseline ( BSL ) and while wearing MAA during sleep . MAA was worn in three positions ( free splints [ FS ] , neutral position [ NP ] , and advanced to 50 % of maximum protrusion [ A50 ] ) for 1 week each in r and om order ( FS-NP-A50 or NP-A50-FS ; titration order , NP-A50 ) . Reports of HA were assessed with pain question naires . RESULTS Overall , sleep variables did not differ across the four nights . SB index decreased up to 60 % with MAA in A50 ( P=.004 ; analysis of variance ) . Snoring was measured as the percentage of sleep time spent snoring . The subgroup of snorers ( n=8 ) showed significant improvement with MAA ( -93 % ; P=.002 ) . Initial HA intensity was reported at 42.7±5/100 mm , showing a decreasing trend with MAA ( -21 % to -51 % ; P=.07 ) . CONCLUSION Short-term use of an MAA appears to reduce SB , snoring , and reports of HA . However , interactions between SB , breathing during sleep , and HA as well as the long-term effectiveness and safety of MAA in adolescents need further investigation |
11,192 | 15,990,949 | Thus , there is little evidence to support the use of hip protectors outside the nursing home setting . | Hip fractures are an important cause of morbidity and mortality in the elderly .
Hip protectors are padded undergarments design ed to decrease the impact of a fall on the hip .
We systematic ally review ed r and omized controlled trials of hip protectors to determine if they reduce hip fractures in the elderly . | The purpose of this in vitro biomechanical study is to determine the force attenuation capacity of four different hip protectors ( KPH1 , KPH2 , Safehip , and Safetypants ) in falling simulations in elderly subjects ( falls to the side ) . The simulated falling conditions were created by a biomechanical testing system , which consisted of an impact pendulum , surrogate pelvis and femur , and two load cells . Three series of impact experiments were conducted in an ascending order ( low , moderate- , and high-force experiments ) , each exceeding the literature -provided average ( + /- 1 SD ) fracture threshold ( 3100 + /- 1200 N ) of the proximal femur of elderly women with a mean age of 71 years . Using a low impact force of 4330 N , the trochanteric soft tissue ( 20-mm-thick polyethylene foam ) attenuated the peak femoral impact force to 3740 N and , accordingly , the KPH1 protector to 590 N , KPH2 to 510 N , Safehip to 1080 N , and Safetypants to 790 N. Thus , in this low force experiment , all tested protectors could reduce the peak impact force entered into the proximal femur below the aforementioned average fracture threshold area ( 3100 + /-1200 N ) of the proximal femur of elderly women . With a moderate impact force of 7230 N , the soft tissue attenuated the peak femoral impact force to 6130 N , and the protectors to 780 N , 760 N , 2240 N , and 2760 N , respectively . Thus , with this impact force , only the KPH hip protectors could reduce the impact force clearly below the fracture threshold area . In the final series of the experiment , the peak femoral impact force was set to be so high ( 10,840 N ) that the protector , if effective , should prevent the hip fracture in almost all cases and situations . The trochanteric soft tissue attenuated this peak impact force to 9190 N , and the tested protectors to 1360 N , 1170 N , 4640 N , and 5770 N. Thus , with the KPH protectors the force received by the proximal femur remained below the average force required to fracture the proximal femur of elderly women , whereas with the two other protectors the impact force entered into the proximal femur clearly exceeded this threshold value . In conclusion , the test results showed that , of the four tested hip protectors , the anatomically design ed energy-shunting and energy-absorbing KPH protectors can provide an effective impact force attenuation in a sideways-fall simulation in the elderly , whereas the force attenuation capacity of the two other protectors seems more limited . However , the true efficacy of any protector in the prevention of hip fractures can only be evaluated in r and omized clinical trials R and omized trials in which the unit of r and omization is a community , worksite , school or family are becoming widely used in the evaluation of life-style interventions for the prevention of disease . The increasing interest in adopting a cluster r and omization design is being matched by rapid method ological developments . In this paper we describe several of these developments . Brief mention is also made of issues related to economic analysis and to the planning and conduct of meta-analyses for cluster r and omization trials . Recommendations for reporting are also discussed OBJECTIVES To investigate the effect of use of external hip protectors on occurrence of hip fracture . DESIGN R and omized controlled trial , with r and omization at the individual level . SETTING residential aged-care facilities in urban areas of New South Wales , Australia . PARTICIPANTS 174 women , aged 75 years and older , who had had two or more falls or one fall requiring hospital admission in the previous 3 months , and who lived in hostels or nursing homes . Eighty-six subjects were in the intervention group and 88 in the control group . INTERVENTION Use of external hip protectors and encouragement by nurses to use the protectors . MEASUREMENTS Follow-up visits at approximately 2 weeks and 2 , 10 and 18 months to determine falls and fall injury ( including hip fracture ) ; we also measured adherence to hip protector use . RESULTS The mean age of participants was 85 ; they lived in 32 different aged-care facilities , two-thirds of which were nursing homes . Intervention and control groups had similar baseline characteristics , with a mean Barthel index of 58 at enrollment and a mean Short Portable Mental Status Question naire score of six errors , indicating severe disability and major cognitive impairment . During follow-up , a mean of 4.6 falls per person occurred . There was no difference in mortality , with 28 deaths in each group . Eight hip fractures occurred in the intervention group and seven in the control group ( hazard ratio 1.46 ; 95 % confidence interval 0.53 - 4.51 ) . No hip fractures occurred when hip protectors were being worn as directed . Adherence was about 57 % over the duration of the study and hip protectors were worn at the time of 54 % of falls in the intervention group . Adherence varied markedly between institutions , but the greatest was about 80 % . CONCLUSION Hip protectors were not effective in reducing the incidence of hip fractures in this study , but because of low statistical power , a reduction in risk of hip fracture of up to 50 % may not have been detected . There was limited adherence with their use , result ing in a large number of falls occurring without hip protectors in place . All hip fractures in the intervention group occurred when hip protectors were not being used Abstract : A method to protect the hips during falls could effectively reduce the incidence of hip fractures . We report the results of the first hip protector trial in Japan , performed between July 1996 , and September 1999 . One hundred and sixty-four elderly female residents of nursing homes , with Activities of Daily Living above the wheelchair level , agreed to participate in this study . Among them , 88 were r and omly selected to wear a hip protector and 76 controls did not . All falls and result ing injuries were recorded daily . In anthropometric measurements and ultrasonic bone evaluation , no significant differences were found between the two groups , except in height . During an average of 377 days , the wearers and the non-wearers fell a total of 131 and 90 times , respectively . Among the wearers , there were two non-hip fractures and one hip fracture , so the annual hip fracture rate was calculated at 1.2 % , against 8 hip fractures among the non-wearers , or 9.7 % per year . The hip fracture rate was significantly lower among the wearers than non-wearers , while the annual number of falls per subject and the distribution of fallers remained the same . According to Cox ’s proportional hazard regression analysis , the effect of the hip protector on hip fracture prevention was independent of anthropometric data , ultrasonic bone assessment values or number of falls . Moreover , even after limiting the subjects to fallers only , the annual hip fracture rate in non-wearers was higher than in wearers ( 19.8 % vs 2.0 % ) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers ( 0.8 % vs 8.2 % ) . It was thus concluded that the hip protector is a beneficial device for the prevention of hip 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 CONTEXT Several r and omized controlled trials have been performed to examine the effectiveness of external hip protectors in reducing the incidence of hip fractures , but the results are controversial . OBJECTIVE To examine the effectiveness of hip protectors in reducing the incidence of hip fractures in an elderly high-risk population . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of elderly persons aged 70 years or older , who have low bone density , and are at high risk for falls . Participants lived in apartment houses for the elderly , homes for the elderly , and nursing homes in Amsterdam and surrounding areas in the Netherl and s. They were enrolled in the study between March 1999 and March 2001 ; the mean follow-up was 69.6 weeks . Of the 830 persons who were screened , 561 persons were enrolled . INTERVENTION External hip protector . Both groups received written information on bone health and risk factors for falls . MAIN OUTCOME MEASURE Time to first hip fracture . Survival analysis was used to include all participants for the time they participated . RESULTS In the intervention group , 18 hip fractures occurred vs 20 in the control group . Four hip fractures in the intervention group occurred while an individual was wearing a hip protector . At least 4 hip fractures in the intervention group occurred late at night or early in the morning . Both in univariate analysis ( log-rank P = .86 ) and in multivariate analysis ( hazard ratio [ HR ] , 1.05 ; 95 % confidence interval [ CI ] , 0.55 - 2.03 ) , no statistically significant difference between the intervention group and control group was found with regard to time to first hip fracture . In addition , the per protocol analysis in compliant participants did not show a statistically significant difference between the groups ( HR , 0.77 ; 95 % CI , 0.25 - 2.38 ) . CONCLUSION The hip protector studied was not effective in preventing hip fractures Abstract : Hip fracture is associated with a higher mortality rate in men than in women . However , mean age of men and women with hip fracture differs markedly . Thus , some of the differences in the clinical pattern and outcome between genders could be related to different ages . To avoid the influence of age on gender-specific outcome , we analyzed prefracture conditions and hip fracture outcome in a cohort of men and of age-matched women . Risk factors for low bone mass were recorded in 106 men ( mean age ± SD , 80.3 ± 9.3 years ) and 264 age-matched women ( mean age 81.4 ± 8.0 ) with hip fracture . We compared mortality rate , survival , years of potential life lost and modification of housing conditions . These outcomes were prospect ively assessed during an average 3.6 years follow-up ( up to 7 years ) . Men with hip fracture differed from age-matched hip-fractured women by a higher alcohol and tobacco consumption , a greater frequency of living in couple , and by less prevalent fractures . Mortality rate after hip fracture was significantly higher in men ( RR = 1.74 , 95 % CI 1.34–2.24 ) . Since mortality is higher in the general male population , we compared reduction in life expectancy taking into account the gender-specific mortality rate . The excess mortality in each age-group of hip-fractured patients , which was measured during the whole follow-up period , and is an estimate of death attributable to fracture , did not differ between genders . Reduction in life expectancy due to hip fracture was similar in both genders ( 5.9 ± 4.5 and 5.8 ± 4.8 years , in men and women , respectively ; NS ) , but the proportion of the years of life lost was higher in men ( 70 ± 33 % ) than in women ( 59 ± 42 % , p < 0.01 ) . It was concluded that for the same age , mortality rate after hip fracture was higher in men than in women . Although the reduction in life expectancy was similar in both genders , the proportion of the years of life lost was higher in men , suggesting a worse impact of hip fracture on survival in men , even after consideration of the higher mortality rate in the general male population Abstract : This study describes the prevalence of osteoporosis in a statewide sample of nursing home residents . Composite forearm bone mineral density ( BMD ) ( including the distal radius and the distal ulna ) of 1475 residents aged 65 years and older from 34 r and omly selected , stratified nursing homes was assessed . BMD was expressed with reference to World Health Organization diagnostic criteria . Trends with age , gender and race were consistent with other population s. However , prevalence estimates were higher than community-based age-specific rates . The prevalence of osteoporosis for white female residents increased from 63.5 % for women aged 65–74 years to 85.8 % for women over 85 years of age . Only 3 % had composite forearm BMD within 1 st and ard deviation of the young adult mean . The significance of the high prevalence of low BMD in nursing home residents is the increased fracture risk it may confer . In community cohorts of white women , the risk of hip fracture increases approximately 50 % for every 1 st and ard deviation decrease in bone mass . However , the degree to which BMD contributes to fracture risk in this population has not been well established BACKGROUND Cluster r and omized trials increasingly are being used in health services research and in primary care , yet the majority of these trials do not account appropriately for the clustering in their analysis . OBJECTIVES We review the main implication s of adopting a cluster r and omized design in primary care and highlight the practical application of appropriate analytical techniques . METHODS The application of different analytical techniques is demonstrated through the use of empirical data from a primary care-based case study . CONCLUSION Inappropriate analysis of cluster trials can lead to the presentation of inaccurate results and hence potentially misleading conclusions . We have demonstrated that adjustment for clustering can be applied to real-life data and we encourage more routine adoption of appropriate analytical techniques OBJECTIVE to assess whether the use of Safehip hip protectors would prevent second hip fractures among men and women living in the community . DESIGN pragmatic r and omised controlled trial . SETTING people living in the community . PARTICIPANTS men and women aged 70 years and over who had sustained one hip fracture and who were living in the community . RESULTS 366 men and women who were either living outside residential care or were about to be discharged back home were r and omised to receive three pairs of hip protectors or to act as controls . Approximately 34 % of participants allocated to receive hip protectors wore them every day . After a median follow up of 14 months 8 participants had a second hip fracture with 6 in the intervention and 2 in the control group ( Odds Ratio for second hip fracture=3.10 , 95 % confidence interval 0.62 - 15.58 ) . Hip protectors had no effect on risk of other fractures or on falls . CONCLUSION this trial does not suggest a benefit of the studied hip protector among people living outside residential accommodation Hip fracture has a significant economic and personal cost , involving hospital admission and functional impairment for elderly people . To assess the benefit of using a newly design ed hip protector ( new material and new design ) to prevent fracture in a realistic setting , a r and omised intervention-control design was used to trial the effectiveness of pads worn by high falls risk residents ( n=71 ) in nursing home for 9 months . 40 residents were in the intervention group and 31 were in the control group . A profile of falls , including time of day , and orientation was obtained to demonstrate the potential effectiveness of the protectors for injury prevention . Acceptance of the hip protector was also surveyed amongst nursing home staff and residents . One hundred and one falls and six fractures occurred in the control group . In contrast , one hundred and ninety one falls and three fractures occurred in the hip protector ( pads ) group . The three fractures in the protector wearing group occurred when pads were not in place . This was extrapolated as 1 in every 16.8 falls and 1 in every 63.7 falls result ing in fracture in the two groups , respectively . The relative risk of fracture was 0.264 ( 95 % CI=0.073 - 0.959 ) when the fracture incidence rate in the intervention group ( three fractures per 191 falls ) was compared to the control group ( six fractures per 101 falls ) . This is a statistically significant result and implies that this newly design ed hip protector is effective in preventing hip fracture . The majority of falls occurred during the day , which was when protectors were worn in this study , but the data on orientation was incomplete , with direction unknown in 74 % of falls . Compliance was an issue , which was interpreted as only 50.3 % of falls recorded with protectors in place . Dementia was identified as the explanation for this as the pads were often removed by these residents who comprised the majority of participants . Perception of low risk was the primary barrier to residents accepting the intervention . Comfort of protectors was not a significant concern for staff or residents , and only staff described appearance as an issue . In conclusion , the newly design ed hip protector is protective against fractures in a realistic setting . Compliance and acceptance of the protectors will ultimately determine the viability of this prophylaxis Objective : To asess whether hip protectors used among women living in the community in the United Kingdom and at high risk of hip fracture , lead to a reduction in hip fracture . Design : Pragmatic r and omized controlled trial ( RCT ) . Setting : Primary care with participants being recruited largely from general practitioners ’ patient lists . Participants : Women aged 70 years and over with one or more risk factors for hip fracture ( i.e. , low body weight , current smoker , a prior fracture , family history of hip fracture ) . Intervention : Three pairs of hip protectors of the “ shell ” type mailed to participants with instructions on how to use them . Main outcome measure : Reduction in hip fractures . Results : 1,388 and 2,781 women aged 70 years or over were r and omized to be given three pairs of hip protectors or act as controls , respectively . We followed up both groups of women for a minimum of 24 months ( maximum 42 months , median 28 ) . Compliance was poor with only 31 % of participants reporting that they wore the hip protectors on a daily basis at 12 months . Intention-to-treat analysis showed that there was no statistically significant difference in the unadjusted odds ratios ( ORs ) of sustaining a hip fracture between the groups ( OR=1.19 ; 95 % confidence interval , 0.80 to 1.78 , p=0.40 ) . Adjustment for important covariates did not material ly change these findings ( OR=1.17 ; 95 % CI , 0.78 to 1.75 ) . Comparing the rate of hip fracture between those women who regularly wore the devices and the control group yielded an OR of 1.12 ( 95 % CI , 0.58 to 2.03 ; p=0.83 ) . Conclusion : This study is the largest RCT of hip protectors to date and provides no evidence of an effect of hip protectors among women living independently and at high risk of fracture 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 In order to prevent hip fractures 548 fall-prone senior citizens living in 20 nursing homes participated in a r and omized controlled trial of hip protectors . One hundred and sixty-four were r and omly selected into the control group and 384 into the intervention group . Of the patients in the intervention group 138 ( 35.9 % ) wore the protector throughout the whole 10 months of the study ’s duration , 124 ( 32.3 % ) quit wearing the protectors after an initial wearing period and 122 ( 31.8 % ) refused to wear them at all . The regular wearers had the protector on during an average of roughly 12 hours a day , so they were protected for 50 % of their exposure time ( including at night ) . Fifty-nine percent of the drop-outs stopped wearing the protectors in the first two study months , mostly for non-medical reasons . Calculation by a forecasting model showed that those senior citizens who were initially prepared to wear the protector tended to be those who were physically restricted Objectives : To investigate the efficacy and effectiveness of hip protectors in frail community living older women . Design : R and omised controlled trial . Setting : Aged care health services in New South Wales , Australia . Patients : 600 women 74 years of age or more ( mean age 83 years ) , who had two or more falls or one fall requiring hospital admission in the previous year , and who lived in their own homes . Intervention : Use of hip protectors . Main outcome measures : Adherence with use of hip protectors , falls , incidence of hip fracture , and adverse effects of use of hip protectors . Results : Adherence was approximately 53 % over the duration of the study and hip protectors were worn at the time of 51 % of falls in the intervention group . The risk of hip fracture when falling while wearing hip protectors , compared with a fall with no hip protectors in place , was significantly reduced ( relative risk ( RR ) 0.23 , 95 % confidence interval ( CI ) 0.08 to 0.67 ) . On an intention to treat analysis , 21 and 22 hip fractures occurred in the intervention and control groups respectively ( adjusted RR 0.92 , 95 % CI 0.51 to 1.68 ) . Three users of hip protectors sustained a hip fracture while wearing properly applied protectors , while 16 hip protector users ( 5 % ) developed minor local complications . Conclusions : Hip protectors prevent hip fractures in community dwelling older women if worn at the time of a fall . The overall effectiveness of hip protectors was not established in this study , because of incomplete adherence with use of the protectors , and limited statistical power OBJECTIVES to evaluate the effectiveness of a policy of making hip protectors available to residents of nursing homes . DESIGN a cluster r and omised controlled trial of the policy in nursing and residential homes , with the home as the unit of r and omisation . SETTING 127 nursing and residential homes in the greater Belfast area of Northern Irel and . PARTICIPANTS 40 homes in the intervention group ( representing 1,366 occupied beds ) and 87 homes in the control group ( representing 2,751 occupied beds ) . INTERVENTIONS a policy of making hip protectors available free of charge to residents of nursing homes and supporting the implementation process by employing a nurse facilitator to encourage staff in the homes to promote their use , over a 72-week period . MAIN OUTCOME MEASURES the rate of hip fractures in intervention and control homes , and the level of adherence to use of hip protectors . RESULTS there were 85 hip fractures in the intervention homes and 163 in the control homes . The mean fracture rate per 100 residents was 6.22 in the intervention homes and 5.92 in the control homes , giving an adjusted rate ratio for the intervention group compared to the control group of 1.05 ( 95 % CI 0.77 , 1.43 , P = 0.76 ) . Initial acceptance of the hip protectors was 37.2 % ( 508/1,366 ) with adherence falling to 19.9 % ( 272/1,366 ) at 72 weeks . CONCLUSIONS making hip protectors available to residents of nursing and residential homes did not reduce the rate of hip fracture . This research does not support the introduction of a policy of providing hip protectors to residents of nursing homes Abstract Objective : To assess the effects of an intervention programme design ed to increase use of hip protectors in elderly people in nursing homes . Design : Cluster r and omised controlled trial with 18 months of follow up . Setting : Nursing homes in Hamburg ( 25 clusters in intervention group ; 24 in control group ) . Participants : Residents with a high risk of falling ( 459 in intervention group ; 483 in control group ) . Intervention : Single education session for nursing staff , who then educated residents ; provision of three hip protectors per resident in intervention group . Usual care optimised by brief information to nursing staff about hip protectors and provision of two hip protectors per cluster for demonstration purpose s. Main outcome measure : Incidence of hip fractures . Results : Mean follow up was 15 months for the intervention group and 14 months for the control group . In total 167 residents in the intervention group and 207 in the control group died or moved away . There were 21 hip fractures in 21 ( 4.6 % ) residents in the intervention group and 42 hip fractures in 39 ( 8.1 % ) residents in the control group ( relative risk 0.57 , absolute risk difference −3.5 % , 95 % confidence interval −7.3 % to 0.3 % , P=0.072 ) . After adjustment for the cluster r and omisation the proportions of fallers who used a hip protector were 68 % and 15 % respectively ( mean difference 53 % , 38 % to 67 % , P=0.0001 ) . There were 39 other fractures in the intervention group and 38 in the control group . Conclusion : The introduction of a structured education programme and the provision of free hip protectors in nursing homes increases the use of protectors and may reduce the number of hip fractures . What is already known on this topic Nursing home residents are at particularly high risk of fracturing a hip Hip protectors can effectively prevent hip fractures Adherence to the use of hip protectors is poor What this study adds The use of hip protectors in nursing homes can be substantially increased by a single session education targeted at nursing staff and residents and provision of free hip protectors Increasing the use of hip protectors result ed in a relative reduction of hip fractures of about 40 BACKGROUND Hip fracture is a common cause of morbidity and mortality in elderly people , for whom osteoporosis , the risk of falling and direct trauma to the hip during the fall are the major risk factors . External hip protectors have been developed which reduce the risk of hip fracture after a fall . However , compliance with their use is uncertain . We addressed this issue in a sample of elderly Dorset rest home residents over a 3-month period . METHODS 31 rest homes agreed to participate . Of the 288 female subjects approached , 141 gave their informed consent and 101 were allocated to the intervention arm of the study . Their ages ranged from 64 to 98 years , and 44 % reported a fall during the preceding 12 months . Each subject was fitted with three pairs of protector pads ( Sahvatex , Denmark ) sewn into specially design ed undergarments . R and omly timed fortnightly visits were made to each subject to assess compliance for 12 weeks . FINDINGS 27 subjects were compliant for the whole study period ; 54 wore the protector pads for less than a week , largely for reasons of poor fitting or discomfort ; the remainder withdrew at varying intervals between 1 and 12 weeks . During the study period , there were nine recorded falls onto the hip , six of which occurred in women wearing protectors . None result ed in hip fracture . CONCLUSION Approximately 50 % of elderly rest home residents who are mentally able would wear hip protectors in order to prevent hip fractures . Long-term compliance drops to about 30 % . Compliance could be increased substantially if the pads and undergarments were modified to enhance their fit and to reduce the discomfort associated with their use The need for clear reporting of r and omized controlled trials has been emphasized recently . The CONSORT Statement has made evidence -based suggestions for a checklist and a patient flow diagram . Adapting this for cluster r and omized controlled trials presents particular challenges . Simple changes in the checklist and diagram for the completely r and omized two level cluster r and omized trials are suggested for discussion . An example taken from an unpublished trial demonstrates that these changes are less simple to implement , although extensions to electronic publications may be helpful . These suggestions should be formally evaluated . Further work is required to consider the cases of more levels and of stratified or pair-matched cluster r and omized trials The first objective of this study was to design a hip protector that would effectively attenuate and shunt away from the greater trochanter the impact energies created in typical falls of the elderly . As the shock absorption material , the protector included the 12 mm-thick Plastazote , which was found to be the most efficient energy-absorbing material in our previous in vitro biomechanical tests . With an anatomically design ed semiflexible outer shield of the protector ( high density polyethylene ) , the impact surface was increased and the impact energy shunted away from the greater trochanter . In the second phase of the study , we determined the force attenuation capacity of this device in realistic ( in vitro ) falling conditions of the elderly . With the impact force of 6940 N used ( a typical hip impact force measured in in vitro falling tests ) , the trochanteric soft tissue ( 25 mm-thick polyethylene foam ) attenuated the peak femoral impact force to 5590 N and the tested protector to 1040 N. In the second series of this experiment , the peak femoral impact force was set to be so high ( 13,130 N ) that the protector , if effective , should prevent the hip fracture in almost all cases . The trochanteric soft tissue attenuated this peak impact force to 10,400 N and the tested protector to 1810 N. Thus , the force received by the proximal femur still remained clearly below 4170 N , the average force required to fracture in vitro the proximal femur of the elderly in a fall loading configuration . In conclusion , our test results suggest that an anatomically design ed energy-shunting and energy-absorbing hip protector can provide an effective impact force attenuation in typical falling conditions of the elderly . However , the efficacy of the protector in the prevention of hip fractures can only be evaluated in r and omized clinical trials Most hip fractures seem to be related to trauma near the hip , so a controlled trial was conducted to investigate the effect of external hip protectors on the prevention of such fractures in residents of a nursing home . 10 of the 28 wards in the nursing home were r and omised to receive external hip protectors ; thus 167 women and 80 men were given protectors and 277 and 141 men no protectors . A fall register was set up for 2 treatment wards ( 45 residents ) and 2 control wards ( 76 residents ) . There were 8 hip and 15 non-hip fractures in the hip-protector group and 31 hip and 27 non-hip fractures in the control group . The relative risk of hip fractures among women and men in the intervention group was 0.44 ( 95 % CI 0.21 - 0.94 ) . None of the 8 residents in the intervention group who had a hip fracture was wearing the device at the time of the fracture . 154 falls were registered and 20 % of these falls produced a direct impact to the hip . In 25 falls direct impact to the hip was sustained at a time when hip protectors were not being worn , and 6 fractures were produced . The study indicates that external hip protectors can prevent hip fractures in nursing-home residents BACKGROUND Hip fractures are common in frail elderly adults worldwide . We investigated the effect of an anatomically design ed external hip protector on the risk of these age-related fractures . METHODS We r and omly assigned 1801 ambulatory but frail elderly adults ( 1409 women and 392 men ; mean age , 82 years ) , in a 1:2 ratio , either to a group that wore a hip protector or to a control group . Fractures of the hip and all other fractures were recorded until the end of the first full month after 62 hip fractures had occurred in the control group . The risk of fracture in the two groups was compared , and in the hip-protector group the risk of fracture was also analyzed according to whether the protector had been in use at the time of a fall . RESULTS During follow-up , 13 subjects in the hip-protector group had a hip fracture , as compared with 67 subjects in the control group . The respective rates of hip fracture were 21.3 and 46.0 per 1000 person-years ( relative hazard in the hip-protector group , 0.4 ; 95 percent confidence interval , 0.2 to 0.8 ; P=0.008 ) . The risk of pelvic fracture was slightly but not significantly lower in the hip-protector group than in the control group ( 2 subjects and 12 subjects , respectively , had pelvic fracture ) ( relative hazard , 0.4 ; 95 percent confidence interval , 0.1 to 1.8 ; P > or = 0.05 ) . The risk of other fractures was similar in the two groups . In the hip-protector group , four subjects had a hip fracture ( among 1034 falls ) while wearing the protector , and nine subjects had a hip fracture ( among 370 falls ) while not wearing the protector ( relative hazard , 0.2 ; 95 percent confidence interval , 0.05 to 0.5 ; P=0.002 ) . CONCLUSIONS The risk of hip fracture can be reduced in frail elderly adults by the use of an anatomically design ed external hip protector Cluster r and omised trials , where groups of patients rather than individuals are r and omised , are increasingly being used in health services research . R and omisation by individual is inappropriate for evaluating some interventions , such as organisational changes , where it may not be feasible to r and omise at the patient level . In such cases cluster r and omisation at the level of the health professional or organisation is necessary . Such r and omisation can also minimise the potential for contamination between treatments when trial patients are managed within the same setting . The main consequence of adopting a cluster design is that the outcome for each patient can no longer be assumed to be independent of that for any other patient ( which is the case in an individually r and omised trial ) . Patients within any one cluster are more likely to have similar outcomes . For example , the management of patients within a single general practice is more likely to be consistent |
11,193 | 25,521,894 | Our results suggest that the risk-benefit ratio related to sensitive research is not unfavorable , but there are gaps in the evidence among adolescents | The neuroscience and psychological literature s suggest that talking about previous violence and abuse may not only be beneficial , as previously believed , but may also be associated with risks .
Thus , studies on such topics introduce ethical questions regarding the risk-benefit ratio of sensitive research . | Members of institutional review boards who evaluate trauma research protocol s frequently face the task of balancing potential risk with potential benefit . However , no known study has examined the relative effect of participating in a trauma-related survey compared to participating in a nontrauma survey . The authors r and omly assigned participants receiving care in an outpatient PTSD treatment program to complete question naires assessing either trauma-related or nontrauma content . Participants completing trauma-related question naires reported feeling sadder and more tense than other participants , though they did not report differences in perceived gain from participation or retrospective willingness to participate . Results suggest that level of distress after participating in trauma research was insufficient to reduce willingness for , or perceived benefit from , participation in trauma survey research Although the number of question naire surveys examining the sequelae of prior sexual and physical victimization has increased over the last decade , little attention has been given to underst and ing the impact of such studies on participants . As part of a larger study of long-term effects of prior sexual and physical victimization , 500 r and omly selected women in an HMO received a comprehensive question naire including multiple symptomatic distress measures and several items inquiring into previous history of sexual , physical , and emotional abuse and neglect . They also completed a short rating scale asking about their reactions to completing the question naire . Despite the sensitive content , the women who participated generally found the experience to be a positive one . Only a small number of women were more upset than they had anticipated , but the vast majority felt they would have completed the survey even if they had known in advance how they would feel . The subset of women who did express distress was significantly different from the group that did not , with respect to other measures of symptomatic distress and trauma exposure . These data suggest that surveys that inquire into prior episodes of childhood victimization are generally well tolerated by women who participate , and that , although a small number may be disturbed by these investigations , in general , adverse reactions may be less common than previously anticipated |
11,194 | 22,543,412 | Surgical intervention within the first 7 weeks yielded greater pain reduction than VCFs treated later .
Conclusions BKP/VP provided greater pain relief and fewer subsequent fractures than NSM in osteoporotic VCFs .
BKP is marginally favored over VP in disability improvement , and significantly favored in QOL improvement .
BKP had a lower risk of cement extravasation and result ed in greater kyphosis correction . | Purpose To determine if differences in safety or efficacy exist between balloon kyphoplasty ( BKP ) , vertebroplasty ( VP ) and non-surgical management ( NSM ) for the treatment of osteoporotic vertebral compression fractures ( VCFs ) . | Summary Bone pain and spinal axial deformity are major concerns in aged patients suffering from osteoporotic vertebral compression fracture ( VCF ) . Pain can be relieved by vertebroplasty or kyphoplasty procedures , in which the compressed vertebral body is filled with substitutes . We r and omly assigned 100 patients with osteoporotic compression fracture at the thoraco-lumbar ( T-L ) junction into two groups : vertebroplasty and kyphoplasty ; we used polymethylmethacrylate ( PMMA ) as the bone filler . Pain before and after treatment was assessed with visual analog scale ( VAS ) scores and vertebral body height and kyphotic wedge angle were measured from reconstructed computed tomography images . More PMMA was used in the kyphoplasty group than in the vertebroplasty group ( 5.56 ± 0.62 vs. 4.91 ± 0.65 mL , p < 0.001 ) . Vertebral body height and kyphotic wedge angle of the T-L spine were also improved ( p < 0.001 ) . VAS pain scores did not differ significantly between the treatment groups . The duration of follow-up was 6 months . Two patients in the kyphoplasty group had an adjacent segment fracture . In terms of clinical outcome there was little difference between the treatment groups . Thus , owing to the higher cost of the kyphotic balloon procedure , we recommend vertebroplasty over kyphoplasty for the treatment of osteoporotic VCFs . Introduction Spinal axial deformities are major concerns in aged patients suffering from osteoporotic vertebral compression fracture . Pain may be relieved by vertebroplasty or kyphoplasty . We investigated the radiological and clinical outcomes of these procedures . Methods One hundred cases of VCF at the thoraco-lumbar junction were r and omly assigned into two groups : vertebroplasty or kyphoplasty ( 50 cases each ) . We used polymethylmethacrylate as the bone filler . Pain before and after treatment was assessed with visual analog scale scores and vertebral body height and kyphotic wedge angle were measured from reconstructed computed tomography images . Results More PMMA was used in the kyphoplasty group than in the vertebroplasty group ( 5.56 ± 0.62 vs. 4.91 ± 0.65 mL , p < 0.001 ) . Vertebral body height and kyphotic wedge angle of the T-L spine were also improved ( p < 0.001 ) . VAS pain scores did not differ significantly between the treatment groups . The duration of follow-up was 6 months . Two patients in the kyphoplasty group had an adjacent segment fracture . Conclusions In terms of clinical outcome there was little difference between the treatment groups . Thus , with the higher cost of the kyphotic balloon procedure , we recommend vertebroplasty over kyphoplasty for the treatment of osteoporotic VCFs In a prospect i ve study , we aim ed to evaluate the potential use of kyphoplasty ( KP ) and vertebroplasty ( VP ) as complementary techniques in the treatment of painful osteoporotic vertebral compression fractures ( VCFs ) . After 1 month of conservative treatment for VCFs , patients with intractable pain were offered treatment with KP or VP according to a treatment algorithm that considers time from fracture ( Δt ) and amount of vertebral body collapse . Bone biopsy was obtained intra-operatively to exclude patients affected by malignancy or osteomalacia . 164 patients were included according to the above criteria . Mean age was 67.6 years . Mean follow-up was 33 months . 10 patients ( 6.1 % ) were lost to follow-up and 154 reached the minimum 2-year follow-up . 118 ( 69.5 % ) underwent VP and 36 ( 30.5 % ) underwent KP . Complications affected five patients treated with VP , whose one suffered a transient intercostal neuropathy and four a subsequent VCF ( two at adjacent level ) . Results in terms of visual analogue scale and Oswestry scores were not different among treatment groups . In conclusion , at an average follow-up of almost 3 years from surgical treatment of osteoporotic VCFs , VP and KP show similar good clinical outcomes and appear to be complementary techniques with specific different indications UNLABELLED This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management . INTRODUCTION Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures . Therefore , we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for > 12 months . MATERIAL S AND METHODS Sixty patients with primary osteoporosis and painful vertebral fractures presenting for > 12 months were included in this prospect i ve , nonr and omized controlled study . Twenty-four hours before performing kyphoplasty , the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty , whereas 20 served as controls . This study assessed changes in radiomorphology , pain visual analog scale ( VAS ) score , daily activities ( European Vertebral Osteoporosis Study [ EVOS ] score ) , number of new vertebral fractures , and health care use . Outcomes were assessed before treatment and at 3 and 6 months of follow-up . All patients received st and ard medical treatment ( 1 g calcium , 1000 IE vitamin D(3 ) , st and ard dose of oral aminobisphosphonate , pain medication , physical therapy ) . RESULTS Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1 % , whereas in the control group , vertebral height decreased by 8.2 % ( p = 0.001 ) . Augmentation and internal stabilization by kyphoplasty result ed in a reduction of back pain . VAS pain scores improved in the kyphoplasty group from 26.2 + /- 2 to 44.2 + /- 3.3 ( SD ; p = 0.007 ) and in the control group from 33.6 + /- 4.1 to 35.6 + /- 4.1 ( not significant ) , whereas the EVOS score increased in the kyphoplasty group from 43.8 + /- 2.4 to 54.5 + /- 2.7 ( p = 0.031 ) and in the control group from 39.8 + /- 4.5 to 43.8 + /- 4.6 ( not significant ) . The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls : mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group ( p = 0.0147 ) . CONCLUSIONS The results of this study show significantly increased vertebral height , reduced pain , and improved mobility in patients after kyphoplasty . Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment BACKGROUND AND PURPOSE : The reported incidence of PCE during PV varies , depending on the sensitivity of diagnostic tests used . To assess the true incidence of PCE , we performed native chest CT during follow-up in a large proportion of patients from the VERTOS II trial . MATERIAL S AND METHODS : VERTOS II is a prospect i ve multicenter r and omized controlled trial comparing PV with conservative therapy in 202 patients . After a mean follow-up of 22 months ( median , 21 months ; range , 6–42 months ) , 54 of 78 patients ( 69 % ) with 80 vertebrae treated with PV underwent native chest CT to detect possible PCE . The presence , location , number , and size of PCE were recorded . In addition , the presence of pulmonary parenchymal changes adjacent to PCE was noted . Possible risk factors for PCE , such as age , sex , number of treated vertebrae , cement volume per vertebra , and presence and location of perivertebral cement leakage , were evaluated . RESULTS : PCE was detected in 14 of 54 patients ( 26 % 95 % CI , 16%–39 % ) . All patients were asymptomatic . Cement emboli were small and r and omly distributed in peripheral small vessels . There were no reactive pulmonary changes . Cement leakage in the azygos vein was the only risk factor for the occurrence of PCE ( OR , 43 ; 95 % CI , 5–396 ) . CONCLUSIONS : Small and clinical ly silent PCE occurred in a quarter of patients treated with PV . Cement leakage into the azygos vein was the only risk factor . With time , these small cement emboli remained inert , without inflammatory pulmonary response . St and ard postprocedural CT or chest radiographs are not necessary BACKGROUND Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures , but there is limited evidence to support its use . METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months ' duration and unhealed , as confirmed by magnetic resonance imaging , were r and omly assigned to undergo vertebroplasty or a sham procedure . Participants were stratified according to treatment center , sex , and duration of symptoms ( < 6 weeks or > or = 6 weeks ) . Outcomes were assessed at 1 week and at 1 , 3 , and 6 months . The primary outcome was overall pain ( on a scale of 0 to 10 , with 10 being the maximum imaginable pain ) at 3 months . RESULTS A total of 78 participants were enrolled , and 71 ( 35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group ) completed the 6-month follow-up ( 91 % ) . Vertebroplasty did not result in a significant advantage in any measured outcome at any time point . There were significant reductions in overall pain in both study groups at each follow-up assessment . At 3 months , the mean ( + /-SD ) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3 , respectively ( adjusted between-group difference , 0.6 ; 95 % confidence interval , -0.7 to 1.8 ) . Similar improvements were seen in both groups with respect to pain at night and at rest , physical functioning , quality of life , and perceived improvement . Seven incident vertebral fractures ( three in the vertebroplasty group and four in the placebo group ) occurred during the 6-month follow-up period . CONCLUSIONS We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures , at 1 week or at 1 , 3 , or 6 months after treatment . ( Australian New Zeal and Clinical Trials Registry number , ACTRN012605000079640 . Previously , we reported significantly reduced pain and improved mobility persisting for 6 months after kyphoplasty of chronically painful osteoporotic vertebral fractures in the first prospect i ve controlled trial . Since improvement of spinal biomechanics by restoration of vertebral morphology may affect the incidence of fracture , long-term clinical benefit and thereby cost-effectiveness , here we extend our previous work to assess occurrence of new vertebral fractures and clinical parameters 1 year after kyphoplasty compared with a conservatively treated control group . Sixty patients with osteoporotic vertebral fractures due to primary osteoporosis were included : 40 patients were treated with kyphoplasty , 20 served as controls . All patients received st and ard medical treatment . Morphological characteristics , new vertebral fractures , pain ( visual analog scale ) , physical function [ European Vertebral Osteoporosis Study ( EVOS ) score ] ( range 0–100 each ) and back-pain-related doctors ’ visits were re-assessed 12 months after kyphoplasty . There were significantly fewer patients with new vertebral fractures of the thoracic and lumbar spine , after 12-months , in the kyphoplasty group than in the control group ( P=0.0084 ) . Pain scores improved from 26.2 to 44.4 in the kyphoplasty group and changed from 33.6 to 34.3 in the control group ( P=0.008 ) . Kyphoplasty treated patients required a mean of 5.3 back-pain-related doctors ’ visits per patient compared with 11.6 in the control group during 12 months follow-up ( P=0.006 ) . Kyphoplasty as an addition to medical treatment and when performed in appropriately selected patients by an interdisciplinary team persistently improves pain and reduces occurrence of new vertebral fractures and healthcare utilization for at least 12 months in individuals with primary osteoporosis BACKGROUND Balloon kyphoplasty is a minimally invasive procedure for the treatment of painful vertebral fractures , which is intended to reduce pain and improve quality of life . We assessed the efficacy and safety of the procedure . METHODS Adults with one to three acute vertebral fractures were eligible for enrolment in this r and omised controlled trial at 21 sites in eight countries . We r and omly assigned 300 patients by a computer-generated sequence to receive kyphoplasty treatment ( n=149 ) or non-surgical care ( n=151 ) . The primary outcome was the difference in change from baseline to 1 month in the short-form (SF)-36 physical component summary ( PCS ) score ( scale 0 - 100 ) between the kyphoplasty and control groups . Quality of life and other efficacy measurements and safety were assessed up to 12 months . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00211211 . FINDINGS 138 participants in the kyphoplasty group and 128 controls completed follow-up at 1 month . By use of repeated measures mixed effects modelling , all 300 r and omised participants were included in the analysis . Mean SF-36 PCS score improved by 7.2 points ( 95 % CI 5.7 - 8.8 ) , from 26.0 at baseline to 33.4 at 1 month , in the kyphoplasty group , and by 2.0 points ( 0.4 - 3.6 ) , from 25.5 to 27.4 , in the non-surgical group ( difference between groups 5.2 points , 2.9 - 7.4 ; p<0.0001 ) . The frequency of adverse events did not differ between groups . There were two serious adverse events related to kyphoplasty ( haematoma and urinary tract infection ) ; other serious adverse events ( such as myocardial infa rct ion and pulmonary embolism ) did not occur perioperatively and were not related to procedure . INTERPRETATION Our findings suggest that balloon kyphoplasty is an effective and safe procedure for patients with acute vertebral fractures and will help to inform decisions regarding its use as an early treatment option BACKGROUND Vertebroplasty is commonly used to treat painful , osteoporotic vertebral compression fractures . METHODS In this multicenter trial , we r and omly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement ( control group ) . The primary outcomes were scores on the modified Rol and -Morris Disability Question naire ( RDQ ) ( on a scale of 0 to 23 , with higher scores indicating greater disability ) and patients ' ratings of average pain intensity during the preceding 24 hours at 1 month ( on a scale of 0 to 10 , with higher scores indicating more severe pain ) . Patients were allowed to cross over to the other study group after 1 month . RESULTS All patients underwent the assigned intervention ( 68 vertebroplasties and 63 simulated procedures ) . The baseline characteristics were similar in the two groups . At 1 month , there was no significant difference between the vertebroplasty group and the control group in either the RDQ score ( difference , 0.7 ; 95 % confidence interval [ CI ] , -1.3 to 2.8 ; P=0.49 ) or the pain rating ( difference , 0.7 ; 95 % CI , -0.3 to 1.7 ; P=0.19 ) . Both groups had immediate improvement in disability and pain scores after the intervention . Although the two groups did not differ significantly on any secondary outcome measure at 1 month , there was a trend toward a higher rate of clinical ly meaningful improvement in pain ( a 30 % decrease from baseline ) in the vertebroplasty group ( 64 % vs. 48 % , P=0.06 ) . At 3 months , there was a higher crossover rate in the control group than in the vertebroplasty group ( 51 % vs. 13 % , P<0.001 ) [ corrected ] . There was one serious adverse event in each group . CONCLUSIONS Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group . ( Clinical Trials.gov number , NCT00068822 . Study Design . A prospect i ve in vivo study was conducted during the performance of kyphoplasty for the treatment of osteoporotic vertebral compression fractures , comparing extravertebral contrast extravasation with kyphoplasty and vertebroplasty . Objective . To determine the frequency and pattern of extravertebral contrast extravasation after intravertebral injection during kyphoplasty and vertebroplasty , which have implication s for cement leakage during these procedures . Summary of Background Data . Vertebroplasty involves the injection of cement directly into the cancellous bone of a fractured vertebral body in an attempt to stabilize the fracture . High rates of extravertebral cement leakage have been noted . Injection of contrast into the vertebral body under fluoroscopy has been recommended in an attempt to predict and minimize cement leakage . An alternative procedure , balloon kyphoplasty , involves the percutaneous placement of an inflatable bone tamp into the fractured vertebral body . As the tamp is inflated , vertebral body height is restored and a cavity is created within the vertebral body , allowing for low-pressure cement filling of the cavity . Methods . During 20 kyphoplasty surgeries for vertebral compression fractures , contrast studies were performed . Immediately after positioning of an 11-gauge biopsy needle within the midvertebral body , 5 mL of Omnipaque was injected , mimicking vertebroplasty injection . Cinefluoroscopic images were obtained during injection . After bilateral fracture reduction and intravertebral cavity creation using inflatable bone tamps ( kyphoplasty ) , contrast was injected again , mimicking cement injection during kyphoplasty . Scoring of the extravertebral contrast leakage was based on filling of the inferior vena cava and epidural vessels , as well as direct contrast extension through the vertebral cortex . Results . The mean contrast leak scores for vertebroplasty- and kyphoplasty-stage injections were , respectively , 4.3 and 0.8 of 6 ( P = 0.0001 ) . The scores for epidural vessel and inferior vena cava filling and transcortical contrast leak each was significantly lower for kyphoplasty- than for vertebroplasty-stage injections ( P = 0.0001 each ) . Conclusions . The findings showed less vascular and transcortical extravasation of injected contrast with kyphoplasty than with vertebroplasty . Although leakage of contrast may not correlate precisely with polymethylmethacrylate leakage , the authors believe this study highlights the relative safety of these procedures PURPOSE To prospect ively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures ( VCF ) treated with percutaneous vertebroplasty ( PV ) compared with optimal pain medication ( OPM ) . METHODS R and omization of patients in 2 groups : treatment by PV or OPM . After 2 weeks , patients from the OPM arm could change therapy to PV . Patients were evaluated 1 day and 2 weeks after treatment . Visual analog score ( VAS ) for pain and analgesic use were assessed before , and 1 day and 2 weeks after start of treatment . Quality of Life Question naire of the European Foundation for Osteoporosis ( QUALEFFO ) and Rol and -Morris Disability ( RMD ) question naire scores were assessed before and 2 weeks after start of treatment . Follow-up scores in patients requesting PV treatment after 2 weeks OPM treatment were compared with scores during their OPM period . RESULTS Eighteen patients treated with PV compared with 16 patients treated with OPM had significantly better VAS and used less analgesics 1 day after treatment . Two weeks after treatment , the mean VAS was less but not significantly different in patients treated with OPM , whereas these patients used significantly less analgesics and had better QUALEFFO and RMD scores . Scores in the PV arm were influenced by occurrence of new VCF in 2 patients . After 2 weeks OPM , 14 patients requested PV treatment . All scores , 1 day and 2 weeks after PV , were significantly better compared with scores during conservative treatment . CONCLUSION Pain relief and improvement of mobility , function , and stature after PV is immediate and significantly better in the short term compared with OPM treatment BACKGROUND Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures , but the efficacy , cost-effectiveness , and safety of the procedure remain uncertain . We aim ed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures . METHODS Patients were recruited to this open-label prospect i ve r and omised trial from the radiology departments of six hospitals in the Netherl and s and Belgium . Patients were aged 50 years or older , had vertebral compression fractures on spine radiograph ( minimum 15 % height loss ; level of fracture at Th5 or lower ; bone oedema on MRI ) , with back pain for 6 weeks or less , and a visual analogue scale ( VAS ) score of 5 or more . Patients were r and omly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated r and omisation codes with a block size of six . Masking was not possible for participants , physicians , and outcome assessors . The primary outcome was pain relief at 1 month and 1 year as measured by VAS score . Analysis was by intention to treat . This study is registered at Clinical Trials.gov , number NCT00232466 . FINDINGS Between Oct 1 , 2005 , and June 30 , 2008 , we identified 431 patients who were eligible for r and omisation . 229 ( 53 % ) patients had spontaneous pain relief during assessment , and 202 patients with persistent pain were r and omly allocated to treatment ( 101 vertebroplasty , 101 conservative treatment ) . Vertebroplasty result ed in greater pain relief than did conservative treatment ; difference in mean VAS score between baseline and 1 month was -5·2 ( 95 % CI -5·88 to -4·72 ) after vertebroplasty and -2·7 ( -3·22 to -1·98 ) after conservative treatment , and between baseline and 1 year was -5·7 ( -6·22 to -4·98 ) after vertebroplasty and -3·7 ( -4·35 to -3·05 ) after conservative treatment . The difference between groups in reduction of mean VAS score from baseline was 2·6 ( 95 % CI 1·74 - 3·37 , p<0·0001 ) at 1 month and 2·0 ( 1·13 - 2·80 , p<0·0001 ) at 1 year . No serious complications or adverse events were reported . INTERPRETATION In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain , percutaneous vertebroplasty is effective and safe . Pain relief after vertebroplasty is immediate , is sustained for at least a year , and is significantly greater than that achieved with conservative treatment , at an acceptable cost . FUNDING ZonMw ; COOK Medical Introduction As life expectancy in the population rises , osteoporotic fractures are seen most frequently in the proximal femur and the vertebral column . In balloon kyphoplasty and vertebroplasty , we have two minimally invasive treatment procedures available . Although they have both been controversially discussed in studies , they have seldom been directly compared . Material s and methods Between 2002 and 2004 , patients with fresh thoracic or lumbar single-segment vertebral compression fractures not involving neurological deficits were treated by balloon kyphoplasty ( n = 30 ) or vertebroplasty(n = 30 ) using PMMA cement , and the results of the two interventions were compared in a prospect i ve , nonr and omised cohort study . Surgery was indicated when patients had painful , dislocated fractures of type A1 and type A3 according to Magerl ’s classification . The outcome of treatment was assessed with special reference to the angle of kyphosis , back pain ( VAS ) , health-related quality of life ( SF-36 ) and complications . Results At the time of the follow-up examination , significant improvement in the angle of kyphosis was found to have been achieved both by kyphoplasty and by vertebroplasty ( P < 0.001 and P = 0.002 , respectively ) . Comparison showed that correction of the angle was significantly ( P < 0.001 ) better in the kyphoplasty group . Both surgical procedures led to significant ( P < 0.001 ) attenuation of the patients ’ pain ; no difference was observed between the groups in the degree of pain relief achieved . There was no demonstrable correlation in either group between the preoperative pain experienced by the patients and the degree of dislocation of their fractures . In both study groups , the quality of life was in keeping with that of a reference group matched for age and sex . Cement leakage was observed in 7 % of patients after kyphoplasty and in 33 % of patients after vertebroplasty ( P = 0.021 ) . Adjacent-level fractures were checked for , but occurred in only one patient in the vertebroplasty group . Conclusion The two surgical procedures were both followed by significant pain relief , and the quality of life was similar regardless of the procedure used . Balloon kyphoplasty led to an ongoing reduction of freshly fractured vertebrae and was followed by a lower rate of cement leakage BACKGROUND Non-r and omised trials have reported benefits of kyphoplasty in patients with cancer and vertebral compression fractures ( VCFs ) . We aim ed to assess the efficacy and safety of balloon kyphoplasty compared with non-surgical management for patients with cancer who have painful VCFs . METHODS The Cancer Patient Fracture Evaluation ( CAFE ) study was a r and omised controlled trial at 22 sites in Europe , the USA , Canada , and Australia . We enrolled patients aged at least 21 years who had cancer and one to three painful VCFs . Patients were r and omly assigned by a computer-generated minimisation r and omisation algorithm to kyphoplasty or non-surgical management ( control group ) . Investigators and patients were not masked to treatment allocation . The primary endpoint was back-specific functional status measured by the Rol and -Morris disability question naire ( RDQ ) score at 1 month . Outcomes at 1 month were analysed by modified intention to treat , including all patients with data available at baseline and at 1 month follow-up . Patients in the control group were allowed to crossover to receive kyphoplasty after 1 month . This study is registered with Clinical Trials.gov , NCT00211237 . FINDINGS Between May 16 , 2005 , and March 11 , 2008 , 134 patients were enrolled and r and omly assigned to kyphoplasty ( n=70 ) or non-surgical management ( n=64 ) . 65 patients in the kyphoplasty group and 52 in the control group had data available at 1 month . The mean RDQ score in the kyphoplasty group changed from 17·6 at baseline to 9·1 at 1 month ( mean change -8·3 points , 95 % CI -6·4 to -10·2 ; p<0·0001 ) . The mean score in the control group changed from 18·2 to 18·0 ( mean change 0·1 points ; 95 % CI -0·8 to 1·0 ; p=0·83 ) . At 1 month , the kyphoplasty treatment effect for RDQ was -8·4 points ( 95 % CI -7·6 to -9·2 ; p<0·0001 ) . The most common adverse events within the first month were back pain ( four of 70 in the kyphoplasty group and five of 64 in the control group ) and symptomatic vertebral fracture ( two and three , respectively ) . One patient in the kyphoplasty group had an intraoperative non-Q-wave myocardial infa rct ion , which resolved and was attributed to anaesthesia . Another patient in this group had a new VCF , which was thought to be device related . INTERPRETATION For painful VCFs in patients with cancer , kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function . FUNDING Medtronic Spine LLC This prospect i ve observational data collection study assessed the cost and quality of life related to hip , vertebral and wrist fracture 1 year after the fracture , based on a patient sample consisting of 635 male and female patients surviving a year after fracture . Data regarding re source use and quality of life related to fractures was collected by question naires at baseline , 4 months and 12 months . Information was collected by the use of patients ’ records , register sources and by asking the patient . Quality of life was estimated with the EQ-5D question naire . Costs were estimated from a societal perspective , including direct and indirect costs . The mean fracture-related cost the year after a hip , vertebral and wrist fracture were estimated , in euros ( € ) , at € 14,221 , € 12,544 and € 2,147 , respectively [ converted from Swedish krona ( SEK ) at an exchange rate of 9.1268 SEK/€ ] . The mean reduction in quality of life was estimated at 0.17 , 0.26 and 0.06 for hip , vertebral and wrist fracture , respectively . Based on the results , the yearly burden of osteoporosis in Sweden could be estimated at € 0.5 billion ( SEK 4.6 billion ) . The patient sample for vertebral fracture was fairly small and included a high proportion of fractures leading to hospitalization , but they indicate a higher cost and loss of quality of life related to vertebral fracture than previously perceived INTRODUCTION Painful fractures of the spine pose a serious clinical problem which gains in importance with the increasing ageing of our population . When conservative treatment of these fractures fails , with vertebroplasty and kyphoplasty we have two percutaneous minimally invasive stabilising procedures at our disposal . PATIENTS AND METHODS We performed a prospect i ve study of 90 patients with fresh osteoporotic vertebral fractures who had been treated with vertebroplasty or kyphoplasty in our clinic between January 1 , 2005 , and December 31 , 2007 . Clinical analysis included Oswestry score and VAS index ; the vertebral body height restoration ( mean vertebral body height , kyphosis angle , anterior/posterior edge ) was evaluated radiologically ; furthermore , all occurring complications were recorded . The follow-up time was 1 year , 80 patients could be examined at follow-up ; 8 patients had died of a tumour disease , lost to follow-up were 2.2 % . RESULTS Both procedures succeeded in significantly ( p<0.001 ) increasing quality of life ( Oswestry score ) and reducing pain ( VAS ) . Following vertebroplasty there were two cases of cement leakage into the spinal canal with consecutive paraparesis which disappeared completely after the cement had been surgically removed . Altogether , 11 adjacent level fractures were observed , 4 in the vertebroplasty and 7 in the kyphoplasty group . CONCLUSION This study compares vertebroplasty and kyphoplasty with regard to their effectiveness , safety , and restoration of vertebral body height , and complications . There were no differences between the groups with regard to quality of life and pain improvement , but the rate of serious complications was higher after vertebroplasty . Mean vertebral body height restoration at 1 year follow-up was significantly higher ( p<0.05 ) in the kyphoplasty group . It remains to be seen in future long-term studies whether or not restoration of vertebral body height has an effect on the clinical result Objective Vertebroplasty ( PV ) and balloon kyphoplasty ( KP ) are minimally invasive vertebral augmentation procedures involving injection of polymethyl methacrylate cement under radiologic control into a fractured vertebral body . They strengthen the bone and improve the intense pain caused by fracture secondary to osteoporosis , metastasis , or trauma and refractory to conservative therapies such as analgesic use , bed rest , and bracing . Aim of the study is to investigate and compare safety and efficacy of KP and PV on pain and mobility in patients with vertebral fractures due to osteoporosis or trauma . Methods Twenty-one patients have been enrolled in a prospect i ve nonr and omized controlled study with painful vertebral compression fractures resistant to common therapies . Patients underwent KP or PV . A Visual Analog Scale has been used to measure pain status at different time up to 6 months ; the Oswestry Disability Index ( ODI ) was chosen to evaluate functional activity before procedure and 6 months later . Results Mean pain scores decreased significantly from pretreatment to posttreatment with KP and PV as did the ODI scores . No significant differences could be found between both groups for the mean VAS and ODI scores preprocedure and postprocedure . Cement extravasation occurred only during PV . No other adverse events correlated to both techniques have been reported . Discussion Our results suggest that both PV and KP offer therapeutic benefit significantly reducing pain and improving mobility in patients with vertebral fracture without significant differences between groups in term of quality . The leakage of cement has been observed only during PV PURPOSE Kyphoplasty and vertebroplasty offer two minimally invasive operative stabilization procedures for vertebral compression fractures . The purpose of this prospect i ve study was to investigate whether both procedures are able to reduce pain and to preserve postoperative vertebral height during a 1-year follow up . MATERIAL S AND METHODS Osteoporotic vertebral fractures were treated in 42 cases , 20 patients ( 15 female , 5 male ) underwent vertebroplasty , 22 patients ( 14 female , 8 male ) underwent kyphoplasty . 32 vertebral fractures were treated with vertebroplasty and 35 vertebral fractures were treated with kyphoplasty . Symptomatic levels were identified by correlating the clinical presentation with conventional radiographs , CT or/ and MRI . During the follow up reduction of pain was determined . Radiographic scans were performed pre- and postoperatively and after 3 , 6 and 12 months . The vertebral height and endplate angles were measured to assess the restoration of the sagittal alignment . The effects on pain symptoms were measured on a self-reported Visual Analog Scale ( VAS ) and the Oswestry score was documented . RESULTS The median pain scores ( VAS ) decreased significantly for kyphoplasty and vertebroplasty from pre- to post-treatment , as did the Oswestry score ( p < 0.05 ) . No significant differences could be found between both groups for the median pain score ( VAS ) and the Oswestry score . Kyphoplsty led to a significant restoration of the vertebral height and reduction of kyphosis ( p < 0.05 ) . During the 1-year follow up both operation techniques were able to stabilize the height of the vertebral body . CONCLUSION Kyphoplasty and vertebroplasty are effective minimally invasive procedures for the stabilization of osteoporotic vertebral fractures leading to a statistically significant reduction in pain . Kyphoplasty restores significantly vertebral body height in fresh fractures . The restoration of vertebral height and reduction of kyphosis may have an influence on the long term clinical outcome . This has to be evaluated in a long term prospect i ve study Older persons who have prevalent vertebral fractures have an increased risk of mortality . It is not known whether incident vertebral fractures are also associated with an increased risk of mortality . To determine whether older women with incident vertebral fractures have an increased risk of mortality , we conducted a prospect i ve cohort study of 7233 community-dwelling older women aged 65 years or older who were enrolled in the Study of Osteoporotic Fractures . We measured incident vertebral fractures by radiographic morphometry of paired lateral spine X-rays taken an average of 3.7 years apart . We also collected information on baseline prevalent vertebral fractures ; calcaneal bone density ; anthropometric measures ; and demographic , medical history , and lifestyle variables . Overall mortality was assessed and confirmed by receipt of death certificates . Over an average of 3.7 years , 389 ( 5.4 % ) women developed at least one incident vertebral fracture . During an additional 8 years of follow-up , 1617 ( 22 % ) women died . Women with at least one new fracture had an age-adjusted 32 % increased risk of mortality ( RH=1.32 ; 95 % CI=1.10–1.58 , P=0.003 ) compared to those without incident vertebral fractures . After adjustment for weight loss , physical frailty markers , and nine other predictors of mortality , there was no longer an independent association between incident vertebral fractures and mortality ( RH=1.06 ; 95 % CI=0.88 1.28 ) . Older women with incident vertebral fractures have an increased risk of mortality that may be explained by weight loss and physical frailty Study Design . A comparative prospect i ve trial evaluating 3-year outcome . Objective . To compare clinical and morphologic outcomes as well as follow-up fractures after kyphoplasty of painful osteoporotic vertebral fractures with calcium-phosphate ( CaP ) cement ( group 1 ) and with polymethylmethacrylate (PMMA)-cement ( group 2 ) . Summary of Background Data . CaP cements seem to be an alternative material for usage in kyphoplasty of vertebral fractures . CaP cements are biodegradable and replaceable by newly formed bone after implantation . Concerns have been raised with regard to the stability of resorbable CaP-cements after implantation into vertebrae post kyphoplasty . Calcibon is a possible CaP cement , which exhibited adequate stability in short-term observations . Material s and Methods . Kyphoplasty was performed in 40 consecutive patients with primary osteoporosis and painful vertebral fractures , 20 received CaP-cement , 20 were treated with PMMA-cement . All patients received a pharmacological antiosteoporosis treatment ( 1000 mg calcium , 1000 IU vitamin D3 , and oral aminobisphosphonate ) , pain medication , and physiotherapy . Pain ( visual analog scale [ VAS ] ; range , 0–100 ) , mobility ( EVOS-score ; range , 0–100 ) and radiomorphologic measurements were assessed at baseline and after 6 , 12 , and 36 months . Results . There were no statistically significant differences between the CaP and PMMA-cement group regarding VAS-scores , EVOS-scores , or height-restoration at any time point . Furthermore , there was no significant difference in the occurrence of vertebral follow-up fractures between both groups during the 3-year follow-up period . Conclusion . CaP cement , e.g. , Calcibon , is as effective and safe as conventional PMMA-cement with regard to immediate and sustained pain reduction and improvement of mobility after kyphoplasty of patients with painful osteoporotic vertebral fractures . CaP cement has the potential of being resorbed and replaced by newly formed bone tissue ; thus , it seems to be a promising alternative for PMMA also in younger patients with painful vertebral fractures OBJECT The aim of this study was to test the hypothesis that kyphoplasty is an effective treatment in painful osteoporotic vertebral fractures , even with involvement of the posterior cortical wall . METHODS Between December 2001 and May 2004 , 74 consecutive patients were treated with kyphoplasty for 118 painful osteoporotic compression ( 38 % ) or burst ( 62 % ) fractures . Additional decompression of the spinal canal was performed in six patients , internal fixation in three . Data were collected in a prospect i ve observational design until May 2005 . The preoperative workup included neuroimaging ( plain x-ray films , densitometry , short tau inversion recovery magnetic resonance imaging , and computed tomography scanning ) and clinical parameters ( general and neurological examinations , visual analog scale [ VAS ] , Karnofsky Performance Scale [ KPS ] , and 36-Item Short Form Health Survey [SF]-36 ) . At predefined time intervals ( at discharge and 6 weeks and 3 , 6 , 12 , and 24 months posttherapy ) the patients were evaluated ( x-ray films , neurological status , VAS , KPS , and SF-36 ) . Kyphoplasty led to a significant reduction in kyphotic deformity ( mean + /- st and ard error of the mean , sagittal index : preoperative 10 + /- 1 degrees , postoperative 5 + /- 1 degrees ) , and an improvement in pain ( VAS : preoperative 70 + /- 3 , postoperative 23 + /- 2 ) , activity ( KPS score : preoperative 51 + /- 3 , postoperative 71 + /- 2 ) , and mental and physical health ( SF-36 , mental status : preoperative 43 , postoperative 58 ; SF-36 , physical status : preoperative 24 , postoperative 35 ) . No secondary narrowing of the spinal canal by the retropulsed posterior wall was observed after the procedure . Clinical improvement was durable ( mean follow up 15 + /- 1.1 months ) , although the VAS score secondarily increased slightly . All patients , who suffered from a compression-induced motor deficit , recovered completely during the follow-up interval . The main procedural complications consisted of one symptomatic extravertebral cement leakage ( permanent monoparesis ) requiring open revision , two nerve root contusions ( transient radiculopathy ) , and one wound infection . CONCLUSIONS Kyphoplasty is effective in the treatment of painful osteoporotic vertebral compression and burst fractures , at least under medium-term conditions . The potential complication of procedure-related secondary narrowing of the spinal canal by the retropulsed posterior wall in burst fractures appears to be more of a theoretical than an actual risk BACKGROUND Ever since Charles Baxter 's recommendations the st and ard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury . A growing number of studies on invasive monitoring in burn shock , however , have raised a debate regarding the adequacy of this regime . The purpose of this prospect i ve , r and omised study was to compare goal -directed therapy guided by invasive monitoring with st and ard care ( Baxter formula ) in patients with burn shock . PATIENTS AND METHODS Fifty consecutive patients with burns involving more than 20 % body surface area were r and omly assigned to one of two treatment groups . The control group was resuscitated according to the Baxter formula ( 4 ml/kg BW/% BSA burn ) , the thermodilution ( TDD ) group was treated according to a volumetric preload endpoint ( intrathoracic blood volume ) obtained by invasive haemodynamic monitoring . RESULTS The baseline characteristics of the two treatment groups were similar . Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group ( P = 0.0001 ) . The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters . Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups . Mortality and morbidity were independent on r and omisation . CONCLUSION Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn . Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration . Increased crystalloid infusion does not improve preload or cardiac output parameters . This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock BACKGROUND The most common complication of osteoporosis is vertebral fractures , which occur more frequently than all other fractures ( hip , wrist , and ankle ) . OBJECTIVE To prospect ively analyze vertebroplasty compared with kyphoplasty for the treatment of osteoporotic vertebral compression fractures using improvement in pain , functional capacity , and quality of life as outcome measures . METHODS The study population included 28 patients in the vertebroplasty group and 24 patients in the kyphoplasty group . The mean follow-up period was 42.2 weeks and 42.3 weeks in the vertebroplasty and kyphoplasty groups , respectively . Outcomes were measured pre- and postoperatively using the visual analogue scale , the Oswestry Disability Index , the EuroQol-5D question naire , and the Short-Form 36 Health Survey . RESULTS In the vertebroplasty group , visual analogue scale scores improved from a mean of 8.0 cm to 5.5 cm at last follow-up ( P = .001 ) . Preoperatively , the Oswestry Disability Index was 57.6 , which improved to 38.4 ( P = .006 ) . The EuroQol-5D score preoperatively was 0.157 and improved to 0.504 ( P = .001 ) . The Short-Form 36 Health Survey showed greatest improvement in the areas of physical health , role physical , body pain , and vitality . In the kyphoplasty group , visual analogue scale scores improved from a mean of 7.5 cm preoperatively to 2.5 cm postoperatively ( P = .000001 ) . The mean Oswestry Disability Index preoperatively was 50.7 and improved to 28.8 ( P = .002 ) . The EuroQol-5D score improved from a mean of 0.234 preoperatively to 0.749 ( P = .00004 ) . The Short-Form 36 Health Survey showed greatest improvement in the areas of physical health , physical functioning , role physical , body pain , and social functioning . CONCLUSION Both vertebroplasty and kyphoplasty are effective at improving pain , functional disability , and quality of life ; however , kyphoplasty provides better results , which are maintained over long-term follow-up Objective : During recent years , the benefits of balloon kyphoplasty and vertebroplasty have been frequently discussed for the treatment of osteoporotic vertebral compression fractures . Because of the lack of comparative studies , we performed an investigation to describe the mechanical effects and the impact on life quality during a follow-up period of 2 years . Methods : Patients with nonrecent fractures of vertebral bodies , ongoing bone remodeling , and major kyphotic deformity were treated with minimal invasive stabilization . The median duration of pain was 8 weeks before surgery . Because of the availability of the equipment , 28 patients were nonr and omly assigned to balloon kyphoplasty and 23 patients to vertebroplasty . The follow-up was performed 2 years after surgery . Results : The kyphotic wedge of the vertebral bodies was decreased 6 ° by balloon kyphoplasty but not by vertebroplasty . With both methods , we found a rapid decrease of pain down to one-half of the preoperative value . A long-lasting effect on pain was found only after balloon kyphoplasty . In the kyphoplasty group , a decrease of the Oswestry Disability Index ( ODI ) score was found during the first postoperative year . After 2 years , the ODI was not different from preoperative values in both groups . Conclusions : In nonrecent fractures , the reduction of the kyphotic wedge by balloon kyphoplasty was superior in decreasing pain persisting over a period of 2 years . The ability to improve disability after kyphoplasty was limited to 1 year . In nonrecent fractures , the consequences of age and osteoporosis seem to equalize the effects of the restored sagittal profile on disability but not on pain Study Design . This study is a retrospective review of 752 patients with adult spinal deformity enrolled in a multicenter prospect i ve data base in 2002 and 2003 . Patients with positive sagittal balance ( N = 352 ) were further evaluated regarding radiographic parameters and health status measures , including the Scoliosis Research Society patient question naire , MOS short form-12 , and Oswestry Disability Index . Objectives . To examine patients with adult deformity with positive sagittal balance to define parameters within that group that might differentially predict clinical impact . Summary of Background Data . In a multicenter study of 298 adults with spinal deformity , positive sagittal balance was identified as the radiographic parameter most highly correlated with adverse health status outcomes . Methods . Radiographic evaluation was performed according to a st and arized protocol for 36-inch st and ing radiographs . Magnitude of positive sagittal balance and regional sagittal Cobb angle measures were recorded . Statistical correlation between radiographic parameters and health status measures were performed . Potentially confounding variables were assessed . Results . Positive sagittal balance was identified in 352 patients . The C7 plumb line deviation ranged from 1 to 271 mm . All measures of health status showed significantly poorer scores as C7 plumb line deviation increased . Patients with relative kyphosis in the lumbar region had significantly more disability than patients with normal or lordotic lumbar sagittal Cobb measures . Conclusions . This study shows that although even mildly positive sagittal balance is somewhat detrimental , severity of symptoms increases in a linear fashion with progressive sagittal imbalance . The results also show that kyphosis is more favorable in the upper thoracic region but very poorly tolerated in the lumbar spine BACKGROUND CONTEXT Defining success after spinal surgery remains problematic . The minimal clinical ly important difference ( MCID ) in pain or functional outcomes is a common metric often calculated independent of perceived risk and morbidity , which is an important consideration in large procedures such as spinal fusion and instrumentation . PURPOSE The purpose of this study was to describe a method of assessing treatment success based on prospect i ve , patient-reported " minimum acceptable " outcome for which they would undergo a procedure . These goals can then be compared at follow-up to gauge how frequently patient goals are met and determine correlation with patient satisfaction . STUDY DESIGN This is a clinical descriptive study of the patient-reported minimum acceptable outcomes for spinal fusion surgery . OUTCOME MEASURES Minimum acceptable outcomes were determined by patients on preoperatively administered st and ard question naires regarding ultimate pain intensity , functional outcome ( Oswestry Disability Index [ ODI ] ) , medication usage , and work status . Satisfaction with outcomes was assessed at 2-year follow-up . METHODS One hundred sixty-five consecutive patients undergoing lumbar fusion for either isthmic spondylolisthesis or disc degeneration were asked to preoperatively define on st and ard question naires their minimum acceptable outcomes after surgery . Two-year outcomes and satisfaction were subsequently reported and compared with the preoperatively determined minimum acceptable outcomes . RESULTS Both the spondylolisthesis and the degenerative disc disease ( DDD ) groups reported that a high degree of improvement was the minimum acceptable threshold for considering spinal fusion . A large majority indicated that the minimum acceptable outcomes included at least a decrease in pain intensity to 3/10 or less , an improvement in ODI of 20 or more , discontinuing opioid medications , and return to some occupational activity . Achieving the minimum acceptable outcome was strongly associated with satisfaction at 2 years after surgery . Patients with compensation cl aims , psychological distress , and other psychosocial stressors were more likely to report satisfaction in the absence of achieving their minimum acceptable outcome . CONCLUSIONS Patients with spondylolisthesis and DDD both have relatively high minimum acceptable outcomes for spinal fusion . In these cohorts , few subjects considered more commonly proposed MCIDs for pain and function as an acceptable outcome and report that they would not have surgery if they did not expect to achieve more than those marginal improvements . Although there was good concordance between achieving the minimum acceptable outcomes and ultimate satisfaction , patients with significant psychosocial factors ( compensation cl aims , psychological distress , and others ) are less likely to associate satisfaction with outcomes with actually achieving these improvements PURPOSE Kyphoplasty immediately improves pain and mobility in patients with painful osteoporotic vertebral fractures , but long-term clinical outcomes are still unclear . This controlled trial evaluates pain , mobility and fracture incidence 3 years after kyphoplasty . MATERIAL S AND METHODS Kyphoplasty was performed in 40 patients with painful osteoporotic vertebral fractures ; 20 patients who were selected for kyphoplasty but chose not to undergo the procedure served as controls . All patients received pharmacologic antiosteoporosis treatment , pain medication , and physiotherapy . Pain ( visual analog scale of 0 - 100 ) , mobility ( European Vertebral Osteoporosis Study question naire score of 0 - 100 ) , and incident vertebral fractures were assessed at baseline , postprocedurally , and after 12 and 36 months . RESULTS Pain score improved after kyphoplasty from 73.8 to 55.9 ( immediately after kyphoplasty ) , 55.6 ( 12 months ) , and 54.0 ( 36 months ; P < .001 ) . Pain score in the control group changed from 66.4 to 65.7 at 12 months and 64.0 at 36 months ( P = .521 ) . The pain score of the kyphoplasty group was significantly improved versus controls after 36 months ( P = .023 ) . Mobility score improved after kyphoplasty from 43.8 to 54.2 ( immediately after kyphoplasty ) , 54.5 ( 12 months ) , and 54.8 ( 36 months ; P = .0008 ) and remained increased ( P = .308 ) compared with controls ( 39.8 immediately after kyphoplasty , 44.3 at 12 months , and 43.6 at 36 months ) . The incidence of new vertebral fractures after kyphoplasty was significantly reduced versus controls after 3 years ( P = .0341 ) . CONCLUSIONS Kyphoplasty reduces pain and improves mobility as long as 3 years after the procedure . The long-term risk of new vertebral fractures after kyphoplasty of chronically painful vertebral fractures is reduced versus controls Introduction It is still controversial whether adjacent level compression fractures after balloon kyphoplasty ( BK ) and vertebroplasty ( VP ) should be regarded as the consequence of stiffness achieved by augmentation with bone cement or if the adjacent level fractures are simply the result of the natural progression of osteoporosis . The purpose of this study was to evaluate the adjacent level fracture risk after BK as compared with VP and to determine the possible dominant risk factor associated with new compression fractures . Material s and methods 73 consecutive patients with painful vertebral compression fractures ( VCFs ) were enrolled in a prospect i ve nonr and omized study . BK was performed in 46 patients ( 51 vertebral bodies ) and VP in 27 patients ( 32 vertebral bodies ) . The first patient ’s visit was before the operative procedure , when clinical and radiographical examinations were done . The follow-up visits , considered in the analysis , were on the first day and after 1 year , postoperatively . Results In 1 year , 3 out of 46 patients ( 6.5 % ) treated with BK , and 2 out of 27 patients ( 7.4 % ) treated with VP sustained adjacent level fracture . More patients with a BMD higher or equal to 3.0 experienced a new fracture than those with a BMD less than 3.0 ( odds ratio = 13.00 ; 95 % confidence interval : 1.35–124.81 ) , and the risk for adjacent level fractures decreased significantly when the postoperative kyphotic angle was less than 9 ° compared with that of higher or equal to 9 ° ( odds ratio = 12.00 ; 95 % confidence interval : 1.25–114.88 ) . Conclusion Our results indicate that BK and VP are methods with a low risk of adjacent level fractures . The most important factors for new VCFs after a percutaneous augmentation procedure are the degree of osteoporosis and altered biomechanics in the treated area of the spine due to resistant kyphosis . These results suggest that the adjacent vertebrae would fracture eventually , even without the procedure . BK and VP offer a comparable rate of pain relief STUDY DESIGN Prospect i ve , double-cohort study . OBJECTIVE To evaluate conservative and percutaneous vertebroplasty ( PV ) management of osteoporotic vertebral fractures . SUMMARY OF BACKGROUND DATA PV is an elective alternative to conservative management for the treatment of a painful osteoporotic vertebral fracture . METHODS We performed a prospect i ve study consisting of 101 consecutive patients who underwent PV and 27 patients who refused PV treatment and were managed conservatively . We used a data evaluation and outcomes system that was developed to evaluate the outcomes of surgical intervention . RESULTS Patients that elected for PV as a treatment of their fractures had significantly more pain and functional impairment before the procedure than the patients of the conservative group ( P < 0.001 ) . The pain , functional , and general health scores of the PV group were improved from the preoperative mean values ( P < 0.001 ) in all postoperative periods . Compared with the conservative treatment group , there was a significant difference at month 3 . However , no statistical differences on function were observed between these groups at 6 months and 1 year posttreatment . CONCLUSIONS PV demonstrated a rapid and significant relief of pain and improved the quality of life . PV election for treatment of painful osteoporotic vertebral fracture after 6 weeks of conservative treatment was based on pain and functional impairment BACKGROUND CONTEXT Kyphoplasty , a minimally invasive technique for fracture reduction and stabilization , has been shown to reduce pain and restore vertebral body height in patients with vertebral compression fractures ( VCFs ) . Analyses comparing treatment outcomes of acute versus chronic VCFs have not yet been reported . PURPOSE To assess whether kyphoplasty results in better clinical outcome and fracture reduction in patients with either acute or chronic VCFs . STUDY DESIGN A prospect i ve , consecutive cohort study of patients who underwent kyphoplasty between March 2000 and December 2001 to treat osteoporotic VCFs that were either less than 10 weeks old ( acute ) or more than 4 months old ( chronic ) . Fifteen subacute fractures ( treated 10 to 16 weeks after fracture ) were excluded from analyses . PATIENT SAMPLE Eighty-six VCFs in 47 patients ( 35 female and 12 male ) were treated during 55 kyphoplasty procedures . Mean patient age was 74 years ( range , 47 to 91 ) . METHODS Clinical outcomes were determined by comparison of preoperative and postoperative data from patient-reported indexes ( pain assessment , pain medication usage and Oswestry Disability Index for Back Pain ) . Radiographs were assessed as to percent vertebral collapse , vertebral height restoration and local kyphosis correction . RESULTS By 2 weeks after surgery , 90 % of acute and 87 % of chronic fractures were associated with pain relief . Narcotic usage decreased and Oswestry scores improved in almost all patients . Mean vertebral body height significantly improved after kyphoplasty ( acute : 58 % to 86 % of estimated normal vertebral height , p < .001 ; chronic : 56 % to 79 % of estimated normal vertebral height , p < .001 ) . Restoration to 89 % or greater estimated normal vertebral height was achieved in 60 % of acute fractures and 26 % of chronic fractures . In addition , more acute fractures were reducible ( greater than 80 % restoration of height lost ) compared with chronic fractures ( p= .01 ) . After kyphoplasty , less than 10 % correction of height lost occurred in 8 % of acute fractures and 20 % of chronic fractures . Local kyphosis significantly improved after kyphoplasty ( mean local Cobb angle : acute , 15 to 8 degrees , p < .001 ; chronic , 15 to 10 degrees , p < .001 ) . CONCLUSION Fracture reduction was best achieved in acute fractures . Symptomatic chronic fractures may also remain c and i date s for kyphoplasty because pain relief and improvement in patient function are reliable and some kyphosis correction can still be achieved in many of these patients Study Design . Clinical r and omized study . Objective . Percutaneous vertebroplasty is compared to conservative treatment in patients with acute or subacute osteoporotic vertebral fractures with respect to pain , physical and mental outcomes . The risk of vertebral fractures adjacent to treated levels is assessed . Summary of Background Data . There are some disagreements of the benefits of PVP for the treatment of acute osteoporotic vertebral fractures , but the long-term clinical outcome of PVP compared to conservative treatment has not been evaluated in a r and omized study . Methods . The 3-months follow-up of this study has been published previously , and here we report the completed 12-months analysis . About 50 patients ( 41 females ) were included from January 2001 until January 2008 . Patients with vertebral fractures less than 8 weeks old were included and r and omized to either PVP or conservative treatment . Pain was assessed with a visual analogue scale . Physical and mental outcomes were assessed by vali date d question naires and tests . Tests , question naires , and plain radiographs were performed at the inclusion and after 3 and 12 months . Results . Pain score before and after the operation in the PVP group was 7.9 and 2.0 , respectively . There was no difference between the groups concerning pain at the 3- and 12-months follow-up . Supplementary assessment of back pain 1 month after discharge from hospital showed a significant lower VAS score in the PVP group over the conservative group . In the study period , 2 adjacent fractures in the PVP group and no adjacent fractures in the conservative group were registered . Conclusion . PVP is a good treatment for some patients with acute/subacute painful osteoporotic vertebral fractures , but the majority of fractures will heal after 8 to 12 weeks of conservative treatment with subsequent decline in pain . The risk of new fractures needs further research CONTEXT Vertebral fractures significantly increase lifetime risk of future fractures , but risk of further vertebral fractures in the period immediately following a vertebral fracture has not been evaluated . OBJECTIVE To determine the incidence of further vertebral fracture in the year following a vertebral fracture . DESIGN AND SETTING Analysis of data from 4 large 3-year osteoporosis treatment trials conducted at 373 study centers in North America , Europe , Australia , and New Zeal and from November 1993 to April 1998 . SUBJECTS Postmenopausal women who had been r and omized to a placebo group and for whom vertebral fracture status was known at entry ( n = 2725 ) . MAIN OUTCOME MEASURE Occurrence of radiographically identified vertebral fracture during the year following an incident vertebral fracture . RESULTS Subjects were a mean age of 74 years and had a mean of 28 years since menopause . The cumulative incidence of new vertebral fractures in the first year was 6.6 % . Presence of 1 or more vertebral fractures at baseline increased risk of sustaining a vertebral fracture by 5-fold during the initial year of the study compared with the incidence in subjects without prevalent vertebral fractures at baseline ( relative risk [ RR ] , 5.1 ; 95 % confidence interval [ CI ] , 3.1 - 8.4 ; P<.001 ) . Among the 381 participants who developed an incident vertebral fracture , the incidence of a new vertebral fracture in the subsequent year was 19.2 % ( 95 % CI , 13.6%-24.8 % ) . This risk was also increased in the presence of prevalent vertebral fractures ( RR , 9.3 ; 95 % CI , 1.2 - 71.6 ; P = .03 ) . CONCLUSION Our data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year Study Design . Clinical r and omized study . Objective . The aim of this study is to compare percutaneous vertebroplasty ( PVP ) to conservative treatment of patients with osteoporotic vertebral fractures in a clinical r and omized study with respect to pain , physical and mental outcome , and to asses the risk of adjacent fractures . Summary of Background Data . PVP is a therapeutic procedure performed to reduce pain in vertebral lesions . Despite the lack of comparative r and omized clinical trials PVP is generally seen as a safe and efficient procedure for painful osteoporotic fractures . Methods . Fifty patients ( 41 females ) were included from January 2001 until January 2008 . Patients with acute ( < 2 weeks ) and subacute ( between 2 and 8 weeks ) osteoporotic fractures were included and r and omized to either PVP or conservative treatment . Pain was assessed with a visual analogue scale and physical and mental outcome were assessed by vali date d question naires and tests . Tests , question naires , and plain radiographs were performed at the inclusion and after 3 months . Results . Reduction in pain from initial visit to 3-month follow-up was comparable in the 2 groups ( P = 0.33 ) from approximate visual analogue scale 8.0 to visual analogue scale 2.0 , intragroup difference was significant ( P = 0.00 ) . Reduction in pain in the PVP group was immediate 12 to 24 hours after the procedure ( P = 0.00 ) . There was no significant difference in the other parameters when comparing the results at inclusion and after 3 months within both groups and between the groups after 3 months with a few exceptions . We observed 2 adjacent fractures in the PVP group and non in the conservative group . Conclusion . The majority of patients with acute or subacute painful osteoporotic compression fractures in the spine will recover after a few months of conservative treatment . The risk of adjacent fractures needs further research . No major adverse events were observed Study Design . A prospect i ve consecutive cohort study of clinical and radiographic outcomes after kyphoplasty for treatment of osteoporotic vertebral compression fractures . Objectives . To measure changes in spinal deformity , activity level , and pain after kyphoplasty treatment . Summary of Background Data . Pain and kyphosis caused by osteoporotic vertebral compression fractures adversely affect quality of life and survival . Kyphoplasty involves the inflation of a balloon bone tamp , percutaneously placed in a fractured vertebral body , followed by deposition of bone cement into the result ing cavity . Previous reports indicate that kyphoplasty improves patient function and restores height of collapsed vertebral bodies , but limited data about the effects of kyphoplasty on spinal sagittal alignment are available . Methods . Twenty-nine patients with osteoporotic vertebral compression fractures who did not respond to medical therapy were treated by kyphoplasty . These patients underwent 37 operations to treat 61 vertebral compression fractures between T6 and L5 . Sagittal alignment was analyzed from st and ing radiographs ( pre- and postkyphoplasty ) . Patient surveys were used to assess pain relief , improvement in activity , and satisfaction with the surgical procedure . Results . In this cohort , a mean of 8.8 ° ( range 0–29 ° ) of correction of local spinal kyphosis was achieved with kyphoplasty . Thirty of 52 fractures ( 17 patients ) were considered reducible and had > 5 ° of correction , with a mean improvement in sagittal alignment of this population of 14.2 ° . Patient surveys revealed significant pain reduction within the first week after surgery and improved activity levels for a majority of patients . Conclusions . Kyphoplasty improves physical function , reduces pain , and may correct kyphotic deformity associated with vertebral compression fractures |
11,195 | 26,888,467 | Conclusions Low-magnitude whole-body vibration therapy can provide a significant improvement in reducing bone loss in the lumbar spine in postmenopausal women .
Moreover , whole-body vibration can be used as an intervention for fall prevention | null | null |
11,196 | 26,553,129 | The most widely applied older person specific instrument was the ICEpop CAPability measure for Older people ( ICECAP-O ) in both community and residential aged care .
Conclusion In the absence of an ideal instrument for incorporating into economic evaluations in the aged care sector , this review recommends the use of a generic preference based measure of health related quality of life such as the EQ-5D to obtain quality adjusted life years , in combination with an instrument that has a broader quality of life focus like the ASCOT , which was design ed specifically for evaluating interventions in social care or the ICECAP-O , a capability measure for older people | Background This paper describes the methods and results of a systematic review to identify instruments used to measure quality of life outcomes in older people .
The primary focus of the review was to identify instruments suitable for application with older people within economic evaluations conducted in the aged care sector . | As more research is undertaken on the elderly , accurately assessing changes in their quality of life becomes increasingly important . Generic instruments are the most popular method to assess quality of life , and one of the most widely used is the EQ-5D . However , the range of dimensions , sensitivity of scales and completion rates have been raised as concerns when using this measure with the elderly . The AQoL is a newer instrument which offers greater richness in dimensions of health covered , and potentially offers greater sensitivity to changes in quality of life . This paper presents the results of a ' head-to-head ' comparison of the EQ-5D and AQoL in terms of practicality , construct validity , agreement ( of absolute scores and their change over time ) and sensitivity to change , as part of a r and omised controlled trial in the elderly . Poor agreement was found between both the absolute scores from each instrument and change in scores over time . Although the AQoL appeared to have more favourable construct validity , the EQ-5D was easier to administer , had a higher completion rate , and appeared more sensitive to change . We conclude that the AQoL is probably less well suited to measuring health status in a very elderly population than the EQ-5D Background Cognition is a multidimensional construct and to our knowledge , no previous studies have examined the independent contribution of specific domains of cognition to health related quality of life . To determine whether executive functions are independently associated with health related quality of life assessed using Quality Adjusted Life Years ( QALYs ) calculated from the EuroQol EQ-5D ( EQ-5D ) in older women after adjusting for known covariates , including global cognition . Therefore , we conducted a secondary analysis of community-dwelling older women aged 65 - 75 years who participated in a 12-month r and omized controlled trial of resistance training . We assessed global cognition using the Mini-Mental State Examination ( MMSE ) and executive functions using the : 1 ) Stroop Test ; 2 ) Trail Making Test ( Part B ) and 3 ) Digits Verbal Span Backwards Test . We calculated QALYs from the EQ-5D administered at baseline , 6 months and 12 months . Results Our multivariate linear regression model demonstrated the specific executive processes of set shifting and working memory , as measured by Trail Making Test ( Part B ) and Digits Verbal Span Backward Test ( p < 0.01 ) respectively , were independently associated with QALYs after accounting for age , comorbidities , general mobility , and global cognition . The final model explained 50 % of the variation in QALYs . Conclusions Our study highlights the specific executive processes of set shifting and working memory were independently associated with QALYs -- a measure of health related quality of life . Given that executive functions explain variability in QALYs , clinicians may need to consider assessing executive functions when measuring health related quality of life . Further , the EQ-5D may be used to track changes in health status over time and serve as a screening tool for clinicians . Trial Registration Clinical Trials.gov Identifier : NCT00426881 Summary Fractures and falls are serious cause of morbidity and cost to society . Our results suggest that the main burden to morbidity , measured as impact on health-related quality of life , is due to fear of falling rather than falls or their sequelae , such as fractures . Introduction Fractures and falls are serious cause of morbidity and cost to society . We investigated the impact on health-related quality of life ( HRQoL ) associated with falls , fractures and fear of falling and falls and fractures cost . Methods Three data sets providing longitudinal data on fear of falling , HRQoL and a common set of baseline risk factors for fracture ( smoking status , weight and age ) were analysed . Multilevel r and om effects models were used to estimate the long-term impact on HRQoL associated with falls , fractures and fear of falling . Healthcare re source use primary data were collected to estimate falls and fractures cost . Results Older , low weight and smoking women reported lower HRQoL. The impact on HRQoL of a fracture was at least twice as large as that associated with falls . The largest negative effect on HRQoL was associated with self-reported fear of falling . The cost of falls was £ 1088 . Similarly , the cost of falls leading to a fracture was £ 15,133 , £ 2,753 , £ 1,863 , £ 1,331 and £ 3,498 for hip , wrist , arm , vertebral and other fractures , respectively . Discussion The main burden to morbidity is due to fear of falling . Interventions aim ed at reducing fear of falling may produce larger gains in OBJECTIVE To estimate the utility ( preference for health ) associated with hip fracture and fear of falling among older women . DESIGN Quality of life survey with the time trade off technique . The technique derives an estimate of preference for health states by finding the point at which respondents show no preference between a longer but lower quality of life and a shorter time in full health . SETTING A r and omised trial of external hip protectors for older women at risk of hip fracture . PARTICIPANTS 194 women aged > /= 75 years enrolled in the r and omised controlled trial or who were eligible for the trial but refused completed a quality of life interview face to face . OUTCOME MEASURES Respondents were asked to rate their own health by using the Euroqol instrument and then rate three health states ( fear of falling , a " good " hip fracture , and a " bad " hip fracture ) by using time trade off technique . RESULTS On an interval scale between 0 ( death ) and 1 ( full health ) , a " bad " hip fracture ( which results in admission to a nursing home ) was valued at 0.05 ; a " good " hip fracture ( maintaining independent living in the community ) 0.31 , and fear of falling 0.67 . Of women surveyed , 80 % would rather be dead ( utility=0 ) than experience the loss of independence and quality of life that results from a bad hip fracture and subsequent admission to a nursing home . The differences in mean utility weights between the trial groups and the refusers were not significant . A test-retest study on 36 women found that the results were reliable with correlation coefficients within classes ranging from 0.61 to 0.88 . CONCLUSIONS Among older women who have exceeded average life expectancy , quality of life is profoundly threatened by falls and hip fractures . Older women place a very high marginal value on their health . Any loss of ability to live independently in the community has a considerable detrimental effect on their quality of life Background There is limited knowledge on the ability of a poor quality of life ( QOL ) and health-related QOL ( HRQOL ) to predict mortality and other adverse health events , independently of the frailty syndrome and other confounders , in older people living in the community and not selected on the basis of specific chronic conditions . Aim of this study was to evaluate the ability of the overall QOL and of the HRQOL to predict several adverse health outcomes at a one-year follow-up in an older outpatient population living in the community . Methods We carried out a prospect i ve cohort study on 210 community-dwelling out patients aged 65 + ( mean age 81.2 yrs ) consecutively referred to a geriatric clinic in Milan , Italy . At baseline participants underwent a comprehensive geriatric assessment including evaluation of overall QOL and HRQOL by means of the Older People 's Quality of Life ( OPQOL ) question naire . At a one-year follow-up , between June and December 2010 , we investigated nursing home placement and death in all 210 participants as well as any fall , any admission to the emergency department ( ED ) , any hospitalisation and greater functional dependence among the subset of subjects still living at home . Results One year after the visit 187 subjects were still living at home ( 89 % ) while 7 had been placed in a nursing home ( 3.3 % ) and 16 had died ( 7.7 % ) . At multiple logistic regression analyses the lowest score-based quartile of the OPQOL total score at baseline was independently associated with a greater risk of any fall and any ED admission . Also , the lowest score-based quartile of the health-related OPQOL sub-score was associated with a greater risk of any fall as well as of nursing home placement ( odds ratio [ OR ] 10.03 , 95 % confidence interval [ CI ] 1.25 - 80.54 , P = 0.030 ) and death ( OR 4.23 , 95 % CI 1.06 - 16.81 , P = 0.041 ) . The correlation with the latter two health outcomes was found after correction for age , sex , education , income , living conditions , comorbidity , disability and the frailty syndrome . Conclusions In an older outpatient population in Italy the OPQOL total score and its health-related sub-score were independent predictors of several adverse health outcomes at one year . Notably , poor HRQOL predicted both nursing home placement and death even after correction for the frailty syndrome . These findings support and enhance the prognostic relevance of QOL measures Background This study aim ed to assess the effects of a risk-based , multifactorial fall prevention programme on health-related quality of life among the community-dwelling aged who had fallen at least once during the previous 12 months . Methods The study is a part of a single-centre , risk-based , multifactorial r and omised controlled trial . The intervention lasted for 12 months and consisted of a geriatric assessment , guidance and treatment , individual instruction in fall prevention , group exercise , lectures on themes related to falling , psychosocial group activities and home exercise . Of the total study population ( n = 591 , 97 % of eligible subjects ) , 513(251 in the intervention group and 262 in the control group ) participated in this study . The effect of the intervention on quality of life was measured using the 15D health-related quality of life instrument consisting of 15 dimensions . The data were analysed using the chi-square test or Fisher 's exact test , the Mann-Whitney U-test and logistic regression . Results In men , the results showed significant differences in the changes between the intervention and control groups in depression ( p = 0.017 ) and distress ( p = 0.029 ) and marginally significant differences in usual activities ( p = 0.058 ) and sexual activity ( p = 0.051 ) . In women , significant differences in the changes between the groups were found in usual activities ( p = 0.005 ) and discomfort/symptoms ( p = 0.047 ) . For the subjects aged 65 to 74 years , significant differences in the changes between the groups were seen in distress ( p = 0.037 ) among men and in usual activities ( p = 0.011 ) among women . All improvements were in favour of the intervention group . Conclusion Fall prevention produced positive effects on some dimensions of health-related quality of life in the community-dwelling aged . Men benefited more than women The objective of this research was to determine the relative decrement in health-related quality of life , as measured by the health utilities index mark 3 ( HUI3 ) , in osteoporosis compared to other chronic medical conditions . The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey ( NPHS ) . The Canadian Multicentre Osteoporosis Study ( CaMos ) is a national population -based study in which regional participants were r and omly recruited , regardless of presence of osteoporosis . We analyzed data from participants aged ≥65 years who completed a baseline HUI3 question naire and provided information on their medical history ( n=3,750 ) . We determined the age- and gender-adjusted mean decrement in HUI3 for several chronic medical conditions , including osteoporosis . The mean changes in HUI3 adjusted for age and gender ( with 95 % confidence intervals ) were as follows : arthritis −0.10 ( −0.11 , −0.09 ) , chronic obstructive pulmonary disease ( COPD ) −0.07 ( −0.09 , -0.05 ) , diabetes mellitus −0.05 ( −0.08 , −0.03 ) , heart disease −0.06 ( -0.08 , −0.04 ) , hypertension −0.02 ( -0.03 , −0.01 ) , and osteoporosis −0.08 ( −0.11 , −0.06 ) , respectively ( model r2=0.17 ; P<0.0001 ) . These findings were comparable to those observed in the NPHS , with the exception of osteoporosis , which had not been previously studied in this fashion . The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions , such as arthritis , COPD , diabetes mellitus or heart disease BACKGROUND The subtrochanteric fracture constitutes approximately 5 - 10 % of all hip fractures . This particular fracture type , owing to its configuration and instability , poses significant challenges to the fixation method , especially in elderly patients with varying degrees of osteoporosis . There has been a gradual change in the operative techniques used to stabilise these fractures leading to the current widespread use of cephalomedullary nails . In contrast to the field of research on patients with the more common femoral neck and trochanteric fractures , few studies have evaluated the health-related quality of life ( HRQoL ) in patients with subtrochanteric fractures . OBJECTIVE To report the long-term outcome for patients with subtrochanteric fractures treated with a cephalomedullary nail with special regard to the HRQoL. SETTING Four university hospitals . DESIGN A prospect i ve cohort study with a 2-year follow-up . PATIENTS AND METHODS Eighty-seven consecutive elderly patients with a subtrochanteric fracture treated with a cephalomedullary nail . Main outcome measurements were mortality rate , reoperation rate , pain at the hip , walking ability , activities of daily living ( ADL ) function and HRQoL assessed with the EQ-5D ( EQ-5D(index ) score ) . RESULTS The EQ-5D(index ) score decreased from 0.73 before fracture to 0.53 at 4 and 12 months and to 0.52 at 24 months . At the final follow-up 80 % of the patients reported no or only limited pain at the hip , 46 % had regained their prefracture walking ability , 48 % their prefracture level of ADL function and 71 % had living conditions similar to those before the fracture . The reoperation rate was 8 % . The mortality rate was 8 % at 4 months , 14 % at 12 months and 25 % at 24 months . CONCLUSIONS A subtrochanteric fracture in elderly patients had a substantial negative effect on both their short and long-term HRQoL. Although pain at the hip was not a major problem there was an obvious deterioration in walking ability and ADL function . However , the rate of revision surgery was comparatively low which confirms that the cephalomedullary nail constitutes a safe treatment for elderly patients with a subtrochanteric fracture . The data on HRQoL obtained in this study can be used in future healthcare evaluations and to calculate quality -adjusted life-years ( QALYs ) The treatment algorithms for displaced fractures of the femoral neck need to be improved if we are to reduce the need for secondary surgery . We have studied 102 patients of mean age 80 years , with an acute displaced fracture of the femoral neck . They were r and omly placed into two groups , treated either by internal fixation ( IF ) with two cannulated screws or total hip replacement ( THR ) . None showed severe cognitive dysfunction , all were able to walk independently , and all lived in their own home . They were review ed at four , 12 and 24 months after surgery . Outcome measurements included hip complications , revision surgery , hip function according to Charnley and the health-related quality of life ( HRQoL ) according to EuroQol ( EQ-5D ) . The failure rate after 24 months was higher in the IF group than in the THR group with regard to hip complications ( 36 % and 4 % , respectively ; p < 0.001 ) , and the number of revision procedures ( 42 % and 4 % , p < 0.001 ) . Hip function was significantly better in the THR group at all follow-up review s regarding pain ( p < 0.005 ) , movement ( p < 0.05 except at 4 months ) and walking ( p < 0.05 ) . The reduction in HRQoL ( EQ-5D index score ) was also significantly lower in the THR group than in the IF group , comparing the pre-fracture situation with that at all follow-up review s ( p < 0.05 ) . The results of our study strongly suggest that THR provides a better outcome than IF for elderly , relatively healthy , lucid patients with a displaced fracture of the femoral neck Background Public policies aim to promote well-being , and ultimately the quality of later life . Positive perspectives of ageing are underpinned by a range of appraoches to successful ageing . This study aim ed to investigate whether baseline biological , psychological and social aproaches to successful ageing predicted future QoL. Methods Postal follow-up in 2007/8 of a national r and om sample of 999 people aged 65 and over in 1999/2000 . Of 496 valid addresses of survivors at follow-up , the follow-up response rate was 58 % ( 287 ) . Measures of the different concepts of successful ageing were constructed using baseline indicators . They were assessed for their ability to independently predict quality of life at follow-up . Results Few respondents achieved all good scores within each of the approaches to successful ageing . Each approach was associated with follow-up QoL when their scores were analysed continuously . The biomedical ( health ) approach failed to achieve significance when the traditional dichotomous cut-off point for successfully aged ( full health ) , or not ( less than full health ) , was used . In multiple regression analyses of the relative predictive ability of each approach , only the psychological approach ( perceived self-efficacy and optimism ) retained significance . Conclusion Only the psychological approach to successful ageing independently predicted QoL at follow-up . Successful ageing is not only about the maintenance of health , but about maximising one 's psychological re sources , namely self-efficacy and resilience . Increasing use of preventive care , better medical management of morbidity , and changing lifestyles in older people may have beneficial effects on health and longevity , but may not improve their QoL. Adding years to life and life to years may require two distinct and different approaches , one physical and the other psychological . Follow-up health status , number of supporters and social activities , and self-rated active ageing also significantly predicted QoL at follow-up . The longitudinal sample bias towards healthy survivors is likely to underestimate these results BACKGROUND The detrimental effects of delirium on functioning and mortality are well known , but health-related quality of life ( HRQoL ) and costs of care have rarely been investigated among patients with delirium . We studied the effects of multicomponent geriatric treatment on costs of care and HRQoL in delirious in patients . METHODS A r and omized , controlled trial of 174 in patients with delirium was performed in an acute geriatric hospital . The intervention was individually tailored geriatric treatment . The HRQoL was measured by the 15D instrument and subjective health by a four-level ordinal scale . Health care costs including intervention costs were calculated for 1 year after the delirium episode . RESULTS Mean age of the patients was 83 years ; 31 % had prior dementia . After the index hospitalization for delirium , a greater proportion in the intervention group than in the control group stated that they felt healthy ( 71 % vs 49 % , p = .050 ) . HRQoL deteriorated in both groups as a consequence of delirium . Deterioration was , however , slower in the intervention group ( -0.026 , 95 % confidence interval [ CI ] , -0.051 to -0.001 ) than in the control group ( -0.065 , 95 % CI , -0.09 to -0.040 ; p = .034 ) . Counting all costs of hospital care , long-term care , skilled home nursing visits , and costs related to intervention , the intervention group used , on average , 19,737 euro during the follow-up year , whereas the respective figure for the control group was 19,557 euro . The difference between the groups was nonsignificant ( 180 euro [ 95 % CI , -5,006 to 5,064 euro ] ) . CONCLUSIONS Comprehensive geriatric intervention improved HRQoL without increasing overall costs of care Background Elderly dialysis patients are prone to disabilities and functional decline . This aggravates their last period of life . It would be valuable to be able to preserve daily function and quality of life . Identification of domains requiring additional attention is not common practice in st and ard care . Therefore , we performed a systematic Comprehensive Geriatric Assessment ( CGA ) to assess physical and psychosocial function and tested its feasibility in daily practice . The CGA is used more frequently in the assessment of elderly cancer patients , and we therefore compared the outcomes to this group . Methods A cross-sectional , multicenter study , between June 1st and September 31st , 2009 , in four Dutch outpatient dialysis units . Fifty patients aged 65 years or above who received dialysis because of end-stage renal disease ( ESRD ) were r and omly included . We assessed the CGA during a systematic interview with patients and their caregivers . The cancer patients had had a similar CGA in an earlier study . We compared prevalences between groups . Results In the dialysis population ( 68.0 % 75 years or above , 76.6 % on haemodialysis ) caregivers often observed behavioral changes , such as deviant eating habits ( 34.0 % ) and irritability ( 27.7 % ) . In 84.4 % , caregivers felt overburdened by the situation of their family member . Somatic and psychosocial conditions were frequently found ( polypharmacy ( 94.6 % ) , depression ( 24.5 % ) ) and prevalence of most geriatric conditions was comparable to those in elderly cancer patients . Conclusions Geriatric conditions were highly prevalent among elderly dialysis patients and prevalences were comparable in both population s. The CGA proved feasible for recognition of these conditions and of overburdened caregivers . This could prevent further functional decline and preserve quality of life Background There is an 80 % prevalence of two or more psychiatric symptoms in psychogeriatric patients . Multiple psychiatric symptoms ( MPS ) have many negative effects on quality of life of the patient as well as on caregiver burden and competence . Irrespective of the effectiveness of an intervention programme , it is important to take into account its economic aspects . Methods The economic evaluation was performed alongside a single open RCT and conducted between 2001 and 2006 . The patients who met the selection criteria were asked to participate in the RCT . After the patient or his caregiver signed a written informed consent form , he was then r and omly assigned to either IRR or UC.The costs and effects of IRR were compared to those of UC . We assessed the cost-utility of IRR as well as the cost-effectiveness of both conditions . Primary outcome variable : severity of MPS ( NPI ) of patients ; secondary outcome variables : general caregiver burden ( CB ) and caregiver competence ( CCL ) , quality of life ( EQ5D ) of the patient , and total medical costs per patient ( TiC-P ) . Cost-utility was evaluated on the basis of differences in total medical costs ) . Cost-effectiveness was evaluated by comparing differences of total medical costs and effects on NPI , CB and CCL ( Incremental Cost-Effectiveness Ratio : ICER ) . CEAC-analyses were performed for QALY and NPI-severity . All significant testing was fixed at p<0.05 ( two-tailed ) . The data were analyzed according to the intention-to-treat (ITT)-principle . A complete cases approach ( CC ) was used . Results IRR turned out to be non-significantly , 10.5 % more expensive than UC ( € 36 per day ) . The number of QALYs was 0.01 higher ( non-significant ) in IRR , result ing in € 276,290 per QALY . According to the ICER- method , IRR was significantly more cost-effective on NPI-sum-severity of the patient ( up to 34 % ) , CB and CCL ( up to 50 % ) , with ICERs varying from € 130 to € 540 per additional point of improvement . Conclusions No significant differences were found on QALYs . In IRR patients improved significantly more on severity of MPS , and caregivers on general burden and competence , with incremental costs varying from € 130 to € 540 per additional point of improvement . The surplus costs of IRR are considered acceptable , taking into account the high societal costs of suffering from MPS of psychogeriatric patients and the high burden of caregivers . The large discrepancy in economic evaluation between QALYs ( based on EQ5D ) and ICERs ( based on clinical ly relevant outcomes ) dem and s further research on the validity of EQ5D in psychogeriatric cost-utility studies . ( Trial registration nr . : IS RCT N 38916563 ; December 2004 ) Objective To evaluate the impact of a provider initiated primary care outreach intervention compared with usual care among older adults at risk of functional decline . Design R and omised controlled trial . Setting Patients enrolled with 35 family physicians in five primary care networks in Hamilton , Ontario , Canada . Participants Patients were eligible if they were 75 years of age or older and were not receiving home care services . Of 3166 potentially eligible patients , 2662 ( 84 % ) completed the vali date d postal question naire used to determine risk of functional decline . Of 1724 patients who met the risk criteria , 769 ( 45 % ) agreed to participate and 719 were r and omised . Intervention The 12 month intervention , provided by experienced home care nurses in 2004 - 6 , consisted of a comprehensive initial assessment using the resident assessment instrument for home care ; collaborative care planning with patients , their families , and family physicians ; health promotion ; and referral to community health and social support services . Main outcome measures Quality adjusted life years ( QALYs ) , use and costs of health and social services , functional status , self rated health , and mortality . Results The mean difference in QALYs between intervention and control patients during the study period was not statistically significant ( 0.017 , 95 % confidence interval −0.022 to 0.056 ; P=0.388 ) . The mean difference in overall cost of prescription drugs and services between the intervention and control groups was not statistically significant , ( −$C165 ( £ 107 ; € 118 ; $ 162 ) , 95 % confidence interval −$C16 545 to $ C16 214 ; P=0.984 ) . Changes over 12 months in functional status and self rated health were not significantly different between the intervention and control groups . Ten patients died in each group . Conclusions The results of this study do not support adoption of this preventive primary care intervention for this target population of high risk older adults . Trial registration Clinical trials NCT00134836 Introduction Long-term outcomes of elderly patients after medical ICU care are little known . The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU . Methods We prospect ively studied 112/230 healthy elderly patients ( ≥65 years surviving at least 12 months after ICU discharge ) with full functional autonomy without cognitive impairment prior to ICU entry . The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III ( APACHE III ) classification diagnosis and length of ICU stay and ICU scores ( APACHE II , Sepsis-related Organ Failure Assessment ( SOFA ) and OMEGA ) at admission and discharge were collected . Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton , Barthel , and Charlson Indexes and Informant Question naire on Cognitive Decline to evaluate functionality , comorbidity and cognitive status , respectively . The EuroQol-5D assessed quality of life . Data were collected at baseline , during ICU and ward stay and 3 , 6 and 12 months after hospital discharge . Paired or unpaired T-tests compared differences between groups ( continuous variables ) , whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables . For variables significant ( P ≤ 0.1 ) on univariate analysis , a forward multiple regression analysis was performed . Results Only 48.9 % of patients ( mean age : 73.4 ± 5.5 years ) were alive 12 months after discharge showing a significant decrease in functional autonomy ( Lawton and Barthel Indexes ) and quality of life ( EuroQol-5D ) compared to baseline status ( P < 0.001 , all ) . Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery ( P < 0.01 , both ) . Thus , in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥40 at discharge the hazard ratio for full functional recovery was 4.04 ( 95 % CI : 1.58 to 10.33 ; P = 0.005 ) and 6.1 ( 95 % CI : 1.9 to 19.9 ; P < 0.01 ) , respectively . Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up ( P < 0.001 ) . Conclusions The survival rate of elderly medical patients 12 months after discharge from the ICU is low ( 49 % ) , although functional status and quality of life remained similar to baseline in most of the survivors . However , there was a two-fold increase in the prevalence of geriatric syndromes Background Health related quality of life ( HRQoL ) in very late life is not well understood . The aim of the present study was to assess HRQoL and health outcomes at four months follow-up in a group of older people awaiting transfer to residential aged care . Methods Secondary analysis of data from a r and omized controlled trial conducted in three public hospitals in Adelaide . A total of 320 patients in hospital beds awaiting a residential aged care bed participated . Outcome measurements included HRQoL ( Assessment of Quality of Life ; AQoL ) , functional level ( Modified Barthel Index ) , hospital readmission rates , survival , and place of residence at four months follow-up . Results In this frail group the median AQoL was poor at baseline ( median 0.02 ; 95%CI -0.01 – 0.04 ) and at follow-up ( 0.05 ; 95%CI 0.03 – 0.06 ) . On leaving hospital , more than one third of participants who were moving for the first time into nursing home care rated themselves in a state worse than death ( AQoL ≤ 0.0 ) . Poor HRQoL at discharge from hospital ( AQoL ≤ 0.0 ) was a significant predictor of mortality ( HR 1.7 ; 95%CI 1.2 – 2.7 ) , but not hospital readmission nor place of residence at four months follow-up . Improved function was a predictor of improved HRQoL among the surviving cohort . Conclusion People making the transition to residential aged care from hospital have very poor HRQoL , but small gains in function seem to be related to improvement . While functional gains are unlikely to change discharge destination in this frail group , they can contribute to improvements in HRQoL. These gains may be of great significance for individuals nearing the end of life and should be taken into account in re source allocation BACKGROUND Falls occur frequently in older people and strongly affect quality of life . Guidelines recommend multifactorial , targeted fall prevention . We evaluated the effectiveness of a multifactorial intervention in older persons with a high risk of recurrent falls . METHODS A r and omized controlled trial was conducted from April 3 , 2005 , to July 21 , 2008 , at the geriatric outpatient clinic of a university hospital and regional general practice s in the Netherl and s. Of 2015 persons identified , 217 persons aged 65 years or older were selected to participate . They had a high risk of recurrent falls and no cognitive impairment and had visited the emergency department or their family physician after a fall . The geriatric assessment and intervention were aim ed at reduction of fall risk factors . Primary outcome measures were time to first and second falls after r and omization . Secondary outcome measures were fractures , activities of daily living , quality of life , and physical performance . RESULTS Within 1 year , 55 ( 51.9 % ) of the 106 intervention participants and 62 ( 55.9 % ) of the 111 usual care ( control ) participants fell at least once . No significant treatment effect was demonstrated for the time to first fall ( hazard ratio , 0.96 ; 95 % confidence interval , 0.67 - 1.37 ) or the time to second fall ( 1.13 ; 0.71 - 1.80 ) . Similar results were obtained for secondary outcome measures and for per- protocol analysis . One intervention participant died vs 7 in the control group ( hazard ratio , 0.15 ; 95 % confidence interval , 0.02 - 1.21 ) . CONCLUSION This multifactorial fall-prevention program does not reduce falls in high-risk , cognitively intact older persons . Trial Registration is rct n.org Identifier : IS RCT N11546541 Background A key goal for services treating older persons is improving Quality of Life ( QoL ) . This study aim ed to 1 ) determine the QoL and utility ( i.e. satisfaction with own quality of life ) for participants of a discharge program for older people following an extended hospital episode of care and 2 ) examine the impact of the intensity of this program on utility gains over time . Methods A prospect i ve observational cohort study with baseline and repeated measures follow up of 351 participants of the transition care program in six community sites in two states of Australia was conducted . All participants who gave consent to participate were eligible for the study . QoL and utility of the participants were measured at baseline , end of program , three and six months post baseline using the EQ-5D and ICECAP-O. Association between the intensity of the program , measured in hours of care given , and improvement in utility were tested using linear regression . Results The ICECAP-O yielded consistently higher utility values than the EQ-5D at all time points . Baseline mean ( sd ) utility scores were 0.55 ( 0.20 ) and 0.75(0.16 ) and at six months were 0.60 ( 0.28 ) and 0.84 ( 0.25 ) for the EQ-5D and ICECAP-O respectively . The ICECAP-O showed a significant improvement over time . The intensity of the post-acute program measured by hours delivered was positively associated with utility gains in this cohort . Conclusions A discharge program for older frail people following an extended hospital episode of care appears to maintain and generate improvements in QoL. The amount of gain was positively influenced by the intensity of the program Background Our research sought to underst and how falls risk , cognitive function , and daily function are associated with health related quality of life ( using the EuroQol-5D ) and quality of life ( using the ICECAP-O ) among older adults with mobility impairments . Methods The EQ-5D and ICECAP-O were administered at 12 months post first clinic attendance at the Vancouver Falls Prevention Clinic . We report descriptive statistics for all baseline characteristics collected at first clinic visit and primary outcomes of interest . Using multivariate stepwise linear regression , we assessed the construct validity of the EQ-5D and ICECAP-O using three dependent measures that are recognized indicators of “ impaired mobility ” – physiological falls risk , general balance and mobility , and cognitive status among older adults . Results We report data on 215 seniors who attended the Vancouver Falls Prevention Clinic and received their first clinic assessment . Patients had a mean age of 79.3 ( 6.2 ) years . After accounting for known covariates ( i.e. , age and sex ) , the ICECAP-O domains explained a greater amount of variation in each of the three dependent measures compared with the EQ-5D domains . Conclusion Both the EQ-5D and ICECAP-O demonstrate associations with falls risk and general balance and mobility ; however , only the ICECAP-O was associated with cognitive status among older adults with mobility impairments . Trial registration Clinical Trials.gov Identifier : Objectives : Cognitive stimulation therapy ( CST ) has shown to have significant benefits in improving the cognitive function and quality of life ( QOL ) in people with mild-to-moderate dementia in a UK r and omized controlled trial ( RCT ) . We developed and examined the Japanese version of group CST ( CST-J ) in a single-blind , controlled clinical trial . Method : CST-J consisting of 14 sessions was administered to a treatment group ( n = 26 ) twice a week for 7 weeks . The treatment group was compared with a control group ( n = 30 ) . Based on single-blindness , cognition was evaluated by a research er , and QOL and mood were rated by the participants themselves . Additionally , QOL and mood of participants were rated by care workers who were not blind but who observed them most directly in their daily life ( important for social validity ) . Results : A linear mixed model was used for analyses of cognition and QOL . There were significant improvements in cognition [ COGNISTAT ( Neurobehavioral Cognitive Status Examination ) and MMSE ( Mini-Mental State Examination ) ] for the treatment group compared with the control group ( p < 0.01 ) . Regarding QOL , the EQ-5D was significant ( p = 0.019 ) and the QoL-AD ( Quality of Life - Alzheimer 's Disease ) showed a positive trend ( p = 0.06 ) when rated by care workers , although not when rated by the participants themselves . Using a nonparametrical analysis , there were significant improvements in the face scale for mood when rated by both the participants ( p < 0.01 ) and the care workers ( p = 0.017 ) . Conclusion : The CST-J shows promising improvements in cognition , mood , and aspects of QOL for people with dementia in Japanese care setting s. A large RCT is now needed Background Expectations held by patients and health professionals may affect treatment choices and participation ( by both patients and health professionals ) in therapeutic interventions in contemporary patient-centered healthcare environments . If patients in rehabilitation setting s overestimate their discharge health-related quality of life , they may become despondent as their progress falls short of their expectations . On the other h and , underestimating their discharge health-related quality of life may lead to a lack of motivation to participate in therapies if they do not perceive likely benefit . There is a scarcity of empirical evidence evaluating whether patients ’ expectations of future health states are accurate . The purpose of this study is to evaluate the accuracy with which older patients admitted for subacute in-hospital rehabilitation can anticipate their discharge health-related quality of life . Methods A prospect i ve longitudinal cohort investigation of agreement between patients ’ anticipated discharge health-related quality of life ( as reported on the EQ-5D instrument at admission to a rehabilitation unit ) and their actual self-reported health-related quality of life at the time of discharge from this unit was undertaken . The mini-mental state examination was used as an indicator of patients ’ cognitive ability . Results Overall , 232(85 % ) patients had all assessment data completed and were included in analysis . Kappa scores ranged from 0.42 - 0.68 across the five EQ-5D domains and two patient cognition groups . The percentage of exact correct matches within each domain ranged from 69 % to 85 % across domains and cognition groups . Overall 40 % of participants in each cognition group correctly anticipated all of their self-reported discharge EQ-5D domain responses . Conclusions Patients admitted for subacute in-hospital rehabilitation were able to anticipate their discharge health-related quality of life on the EQ-5D instrument with a moderate level of accuracy . This finding adds to the foundational empirical work supporting joint treatment decision making and patient-centered models of care during rehabilitation following acute illness or injury . Accurate patient expectations of the impact of treatment ( or disease progression ) on future health-related related quality of life is likely to allow patients and health professionals to successfully target interventions to priority areas where meaningful gains can be achieved Summary Using two instruments ( SF-6D and EQ-5D ) to estimate quality adjusted life years ( QALYs ) , we conducted an economic evaluation of a 12-month r and omized controlled trial with a 12-month follow-up study in older women to evaluate the value for money of two doses of resistance training compared with balance and tone classes . We found that the incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D . Introduction Decision makers must continually choose between existing and new interventions . Hence , economic evaluations are increasingly prevalent . The impact of quality -adjusted life year ( QALY ) estimates using different instruments on the incremental cost-effectiveness ratios ( ICERs ) is not well understood in older adults . Thus , we compared ICERs , in older women , estimated by the EuroQol-5D ( EQ-5D ) and the Short Form-6D ( SF-6D ) to discuss implication s on decision making . Methods Using both the EQ-5D and the SF-6D , we compared the incremental cost per QALY gained in a r and omized controlled trial of resistance training in 155 community-dwelling women aged 65 to 75 years . The 12-month r and omized controlled trial included a subsequent 12-month follow-up . Our focus , the follow-up study , included 123 of the 155 participants from the Brain Power study ; 98 took part in the economic evaluation ( twice-weekly balance and tone exercises , n = 28 ; once-weekly resistance training , n = 35 ; twice-weekly resistance training , n = 35 ) . Our primary outcome measure was the incremental cost per QALY gained of once- or twice-weekly resistance training compared with balance and tone exercises . Results At cessation of the follow-up study , the incremental QALY was −0.051 ( EQ-5D ) and −0.144 ( SF-6D ) for the once-weekly resistance training group and −0.081 ( EQ-5D ) and −0.127 ( SF-6D ) for the twice-weekly resistance training group compared with balance and tone classes . Conclusion The incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D . Given the large magnitude of difference , the choice of preference-based utility instrument may substantially impact health care decisions We studied the impact of CHOP chemotherapy on the quality of life ( QoL ) of elderly patients with aggressive non-Hodgkin 's lymphoma ( NHL ) . 132 patients aged 65 or older , who participated in a r and omized , multicenter trial , completed QoL question naires ( EuroQol-5D , EORTC QLQ-C30 and MFI-20 ) on 8 predefined time-points before , during and following treatment . At baseline , QoL was significantly better on almost all dimensions in patients with a lower compared to patients with a higher age-adjusted International Prognostic Index ( aaPI ) . During treatment , physical and role functioning and global QoL deteriorated and fatigue increased in the lower aaPI group , whereas QoL of the higher aaPI group remained stable . During follow-up , the QoL was significantly better for patients in complete response ( CR ) or partial remission ( PR ) than for patients with progression/relapse . Soon after completion of therapy , the QoL of the lower aaPI group returned to pretreatment levels or better , while patients with higher aaPI showed a significant improvement in QoL compared to baseline levels . The effect of CHOP on the quality of life of elderly patients could be used in counseling this group of patients BACKGROUND AND PURPOSE Physical activity and exercise as part of cardiac rehabilitation after an acute coronary event improves exercise capacity and quality of life in most patients . The aim of the present study was to evaluate physical activity level , health-related quality of life ( HRQL ) and perceived health three to six years after an acute myocardial infa rct ion or an episode of unstable angina pectoris in elderly patients and compare this to earlier follow-up examination data . METHOD STUDY DESIGN three to six years ( mean 4.4 years ) after r and omization a question naire about physical activity level , HRQL and perceived health was mailed to all subjects alive ( n = 93 ) ( response rate 96 % ) . The original study population consisted of 101 patients aged > or = 65 years admitted to the Coronary Care Unit at the Karolinska Hospital because of an acute coronary event between 1994 and 1997 . The patients were r and omized to either a three-month period of aerobic group training three times a week ( n = 50 ; acute myocardial infa rct ion 29 , unstable angina pectoris 21 ) or served as control subjects ( n = 51 ; acute myocardial infa rct ion 31 , unstable angina pectoris 20 ) . RESULTS Since the one-year follow-up examination eight subjects had died : five in the intervention group and three in the control group . At r and omization , the level of physical activity level was similar in the two groups . Those in the intervention group improved their level of physical activity significantly over time ( p = 0.05 ) in contrast to the control group . Measurements of HRQL showed no statistical difference between the groups by use of the EuroQol instrument . However , a small advantage for the intervention group measured over time was noted . CONCLUSION It is important to include elderly patients in cardiac rehabilitation programmes after an acute coronary event , since even a short period of supervised exercise training has the potential to positively influence physical activity level for as long as three to six years Objective : To determine differences in outcome between undisplaced ( Garden I and II ) and displaced ( Garden III and IV ) femoral neck fractures in elderly patients treated with internal fixation . Setting : University hospital . Design : Prospect i ve clinical study . Patients : Ninety patients with an acute femoral neck fracture after a fall . The inclusion criteria were age older than sixty‐five years , absence of severe cognitive dysfunction , independent living , and unhindered walking capability preoperatively . The mean follow‐up was twenty‐six months . Intervention : The patients were treated with closed reduction and percutaneous internal fixation with two cannulated screws . Main Outcome Measurements : Fracture healing complications , pain ( visual analogue scale ) , walking capability , activities of daily living , and quality of life according to EuroQol . Results : The rate of fracture healing complications in displaced femoral neck fractures in patients available at the final follow‐up was 36 percent compared with 7 percent in patients with undisplaced fractures . The quality of life , according to Euro‐Qol , of patients with uneventfully healed fractures was significantly lower in patients with primarily displaced fractures ( 0.51 ) than in patients with undisplaced ones ( 0.76 ) . Conclusion : There was a major difference in outcome on comparing undisplaced and displaced femoral neck fractures in elderly patients treated with internal fixation . The rate of fracture healing complications in patients with undisplaced fractures was low , and patients with healed fractures regained their prefracture quality of life level . The rate of fracture healing complications and reoperations in patients with displaced fractures was high , and even in patients with uneventfully healed fractures , there was a substantial decrease in the quality of life Purpose There is a growing population of older people living alone within the context of dramatic population ageing and changing living arrangements . However , little is known about the quality of life ( QoL ) of older people living alone in Mainl and China . This study aim ed to investigate QoL and its related factors among Chinese older people who live alone . Methods A stratified r and om cluster sample of 521 community-dwelling older people living alone in Shanghai completed a structured question naire through face-to-face interviews . QoL was measured using the Older People ’s Quality of Life Question naire . Other data collected included self-rated health , physical health , cognitive function , depression , functional ability , loneliness , social support , physical activity , health services satisfaction , satisfaction with overall dwelling conditions and socio-demographic variables . Results Older people living alone in Mainl and China rated social relationships and financial circumstances as sources of low satisfaction within their QoL. Multiway analysis of variance showed that satisfaction with overall dwelling conditions , self-rated health , functional ability , depression , economic level , social support , loneliness , previous occupation and health services satisfaction were independently related to QoL , accounting for 68.8 % of the variance . Depression and previous occupation had an interaction effect upon QoL. Conclusions This study identified nine factors influencing the QoL of older people living alone in Mainl and China . Interventions to increase satisfaction with dwelling conditions , improve economic level , social support and functional ability , decrease loneliness and depression and improve health services satisfaction appear to be important for enhancing their The main purpose of this prospect i ve study was to investigate the functional outcome and health-related quality of life according to EuroQol ( EQ-5D ) after a femoral neck fracture treated with internal fixation in relatively healthy elderly patients . We also aim ed to vali date the use of the EQ-5D in routine clinical follow-ups of this group of patients . The inclusion criteria were more than 65 years of age , absence of severe cognitive dysfunction , living independently , and unhindered walking ability preoperatively . The mean follow-up period was 17 months . The rated prefracture EQ-5Dindex scores showed good correspondence with the scores of an age-matched Swedish reference population . The EQ-5Dindex scores decreased from 0.78 before the fracture ( based on recall ) to 0.59 at 4 months and 0.51 at 17 months after surgery . The decrease was significantly larger among patients with fracture healing complications . There was a good correlation between the EQ-5Dindex scores and other outcome measures such as pain , mobility , independence in ADL and independent living status . The question naire response rate ( EQ-5D ) was 89–100 % on different follow-up occasions . The EQ-5D appears to be an easy-to-use instrument even for elderly patients with femoral neck fractures . Changes in the quality of life may be useful to identify patients who might benefit from reoperation , i.e. arthroplasty . The EQ-5D also appears to be a relevant clinical end-point in outcome studies OBJECTIVE The goal of this study was to estimate an algorithm to convert responses to the Functional Assessment of Cancer Therapy - General ( FACT-G ) to time trade-off ( TTO ) utilities based on utilities for current health elicited from cancer patients . METHODS Data for 1433 cancer patients were r and omly separated into construction and validation sample s. Four FACT-G questions were selected for inclusion based on correlation with Eastern Clinical Oncology Group - Performance Status ( ECOG-PS ) scores and TTO utilities . Item response theory was used to collapse response categories . Ordinary least squares regression with the constant constrained to one was used to estimate the algorithm . RESULTS The algorithm estimated mean utility for the full validation sample within three points of observed mean utility ( 0.805 vs. 0.832 , P < 0.01 ) . Mean utilities were well predicted ( mean absolute difference < 0.03 , P > 0.05 ) for most subgroups defined by ECOG-PS and Short Form-36 physical functioning scores , and responses to the FACT-G overall quality of life item . Nevertheless , the algorithm systematic ally overpredicted utilities for poorer health states . CONCLUSIONS A FACT-G-based algorithm of cancer patient utilities was developed that estimates group mean utility scores with accuracy comparable to other indirect preference-based measures of health-related quality of life . Patient-based preferences for health outcomes of cancer treatment may be useful in multiple situations , such as managing re sources within cancer centers and in underst and ing health states preferences among cancer experienced patients before and after treatment OBJECTIVE To determine the factors that predict change in well-being over time in older men and women presenting to the falls prevention clinic . DESIGN Prospect i ve cohort study . SETTING Falls prevention clinic . PARTICIPANTS Community-dwelling older adults who were referred to the clinic after sustaining a fall ( between N=244 and N=255 , depending on the analysis ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The ICEpop CAPability measure for Older people , a measure of well-being or quality of life , was administered at baseline , 6 months , and 12 months . We constructed linear mixed models to determine whether baseline predictor variables were related to baseline well-being and /or changes in well-being over time . In addition , we included interactions with sex to investigate the difference between men and women . Baseline predictors included 2 measures of mobility -- Short Performance Physical Battery and timed Up and Go test-- and a measure of global cognitive function -- Montreal Cognitive Assessment . RESULTS All 3 predictors were associated with well-being at baseline ( P<.05 ) . Furthermore , both the Short Performance Physical Battery and the timed Up and Go test interacted with sex ( P<.05 ) to predict changes in well-being over time . Follow-up analyses suggested that better mobility was protective against decline in well-being in men but was generally unrelated to changes in well-being in women . CONCLUSIONS We found that 2 valid and reliable measures of mobility interacted with sex to predict changes in well-being over time . This is a critical research area to develop in order to appropriately tailor future intervention strategies targeting well-being in older fallers , a population at high risk of functional decline The assessment of the validity and reliability of generic quality of life ( QoL ) instruments among elderly patient groups has tended to lag behind such assessment s in general population s , yet it is an important method ological issue . This paper presents the findings from a study of the use of the EuroQoL among an elderly acute care patient group , focusing particularly on the ability to self-complete , construct validity and sensitivity to change . Two hundred and fourteen UK patients aged 65 years and over , participating in a r and omized controlled trial comparing hospital at home and routine hospital care were asked to complete the EuroQoL and a number of other instruments at r and omization and at 4 week and 3 month follow-ups . The inability to self-complete the EuroQol was found to be strongly related to both increased age and reduced cognitive function ( p < 0.0001 ) . From logistic regression , the expected probability of an acute care patient requiring interview administration at age 65 years is 11 % , at age 75 years is 37 % and at age 85 years is 73 % . The relationships with age and limiting long-st and ing illness/disability were weaker than expected , but the results obtained from the EuroQoL were highly correlated with those from both the Barthel index and the COOP-WONCA charts where this was anticipated . Preliminary evidence of sensitivity to change was found from descriptive statistics of the changes in scores for four specific subgroups of patients , but the small numbers and high variability in each sub- sample means that this should be interpreted with caution . The most important issue arising from the research concerns the impact of age on the ability to self-complete the EuroQoL question naire . It is argued that this research points to the need for rigorous studies ( such as r and omized controlled trials ) to assess the impact of the format of administration of the EuroQoL on the scores obtained Objective To evaluate the effect of specialist geriatric medical management on the outcomes of at risk older people discharged from acute medical assessment units . Design Individual patient r and omised controlled trial comparing intervention with usual care . Setting Two hospitals in Nottingham and Leicester , UK . Participants 433 patients aged 70 or over who were discharged within 72 hours of attending an acute medical assessment unit and at risk of decline as indicated by a score of at least 2 on the Identification of Seniors At Risk tool . Intervention Assessment made on the acute medical assessment unit and further outpatient management by specialist physicians in geriatric medicine , including advice and support to primary care services . Main outcome measures The primary outcome was the number of days spent at home ( for those admitted from home ) or days spent in the same care home ( if admitted from a care home ) in the 90 days after r and omisation . Secondary outcomes were determined at 90 days and included mortality , institutionalisation , dependency , mental wellbeing , quality of life , and health and social care re source use . Results The two groups were well matched for baseline characteristics , and withdrawal rates were similar in both groups ( 5 % ) . Mean days at home over 90 days ’ follow-up were 80.2 days in the control group and 79.7 in the intervention group . The 95 % confidence interval for the difference in means was −4.6 to 3.6 days ( P=0.31 ) . No significant differences were found for any of the secondary outcomes . Conclusions This specialist geriatric medical intervention applied to an at risk population of older people attending and being discharged from acute medical units had no effect on patients ’ outcomes or subsequent use of secondary care or long term care The research presented here aim ed to obtain population norms on pertinent domains of quality of life and health related quality of life , and the relative importance of these domains to people . The OPCS Omnibus Survey was used as the vehicle for the study . This is a monthly survey of a r and om sample of 2000 adult members of the population in Great Britain , based on a r and om sample of households . The data was collected for a one month period . The response rate to the survey was 77 % . In response to a generic question about the five ( priority ordered ) most important things in their lives ( good or bad ) , respondents were most likely to freely mention as the first most important thing in their lives relationships with family or relatives , followed by their own health , the health of another ( close ) person and finances/st and ard of living/housing . When responses relating to respondents ' priority ranked areas 1 - 5 were combined , the most frequently mentioned area of life was finances/st and ard of living/housing , followed by relationships with family and friends , own health , the health of close others and social life/leisure activities . Thus , different distributions were obtained depending on whether priority ordering or frequency with which item was mentioned was analysed . Of those who reported a longst and ing illness , the conditions which were most likely to be reported as affecting their lives were respiratory conditions , joint disorders and heart and circulatory diseases . The most commonly freely mentioned first most important effects of the longst and ing illness on their lives were ( in order of frequency ) ability to get out and about/st and /walk/go out shopping , being able to work/find a job and effects on social life/leisure activities ( based on office coding from verbatim responses recorded on the question naire ) . When the responses relating to respondents ' priority ranks 1 - 5 were combined , the most frequently mentioned area of life affected was ability to get out and about/st and /walk/go out shopping , followed by social life/leisure activities , and availability of work/ability to work . Again , differences in distributions were obtained depending on the method of analysis . Further investigations also revealed differences according to the method of question ing and coding ( respondent vs office ) . When respondents selected their own codes from a showcard in relation to health effects , there were some discrepancies with their ( office coded ) verbatim replies ( which were recorded by the interviewer before they saw the showcard , for later office coding ) . The showcard had the effect of prompting them , and the then most commonly mentioned first most important effects of the longst and ing illness on their lives were ( in order of frequency ) pain , tiredness/lack of energy/lethargy , social life/leisure activities , and availability of work/ability to work . This discrepancy illustrates the biasing influence of using showcards , in comparison with the open coding of actual verbatim responses back in the office ( on the assumption that the latter are more valid-unprompted-responses ) . Analysis of the domains included in the most popularly used health status scales , which are used to measure health related quality of life , revealed that several items ranked as important by the public were missing OBJECTIVES To apply diagnostic criteria for mild cognitive impairment ( MCI ) to a geographically representative sample , to estimate the prevalence of MCI , and to estimate 10-year trajectories of incident disability for cognitively intact participants and subgroups with MCI . DESIGN Prospect i ve cohort ; 10 years of follow-up . SETTING Community-based survey of noninstitutionalized population aged 65 and or older in two rural Iowa counties ( Washington and Iowa ) . PARTICIPANTS Iowa Established Population s for Epidemiologic Studies of the Elderly ( aged > or = 65 ; N = 3,673 ; 61.3 % female ; 99.9 % white ) . MEASUREMENTS Age , sex , education , Short Portable Mental Status Question naire ( SPMSQ ) , 20-item word recall , activities of daily living ( ADLs ) , instrumental activities of daily living ( IADLs ) , chronic medical conditions . RESULTS MCI was prevalent in 24.7 % of participants at baseline . Most participants in the overall cohort remained stable or changed slowly ( < or = 1 new limitations ) over 10 years ( 63.1 % for SPMSQ , 89.3 % for word recall , and 61.7 % for ADL disability ) . For MCI/no prevalent IADL disability ( Stage 1 MCI ) , disability progression was similar to that in the cognitively intact subgroup ( median = 0.08 vs 0.05 disabilities per year ) . For MCI plus prevalent IADL disability ( Stage 2 MCI ) , the median rate of change was equivalent to that of the severely impaired ( 0.23 disabilities per year ; interquartile range = 0.12 - 0.36 ) . CONCLUSION Unlike participants with MCI who reported no IADL limitations , those with such limitations were more likely to develop ADL disability -- a prerequisite for a diagnosis of dementia Purpose The aim of this study was to assess mortality in healthy elderly patients after non-elective medical ICU admission and to identify predictive factors of mortality in these patients . Methods Patients ≥65 years living at home and with full-autonomy ( Barthel index , BI > 60 ) , without cognitive impairment , and non-electively admitted to a medical ICU were prospect ively recruited . A full comprehensive geriatric assessment was made with vali date d scales . Results A total of 230 patients were included , 110 ( 48 % ) between 65 and 74 years and 120 ( 52 % ) ≥75 years . No significant differences were observed between the two groups in premorbid functional and cognitive status , main diagnosis at ICU admission , APACHE II and SOFA scores , use of mechanical ventilation or haemodialysis or length of ICU stay . Over a mean follow-up of 522 days ( range 20–1,170 days ) the cumulative mortality of the whole group was 55 % , being significantly higher in older subjects ( 62 vs. 47 % ; P = 0.024 ) . On multivariate analysis , only parameters related to quality of life ( QOL ) and functional status were independent predictors of cumulated mortality ( P < 0.01 , both ) . Thus , in patients with EQ-5Dvas ( < 70 ) or baseline Lawton index ( LI ) ( < 5 ) the hazard ratio for cumulated mortality was 2.45 ( 95 % CI : 1.15–5.25 ; P = 0.03 ) and 4.10 ( 95 % CI : 1.53–10.99 ; P = 0.006 ) , respectively , compared to those with better scores . Conclusions Healthy elderly non-elective medical patients admitted to the ICU have a high mortality rate related to premorbid QOL . The LI and /or EQ-5Dvas may be useful tools to identify patients with the best chance of survival Objectives : To evaluate the responsiveness of the EuroQol ( EQ-5D ) and Short-Form 36 ( SF-36 ) instruments , i.e. their ability to capture clinical ly important changes , in elderly patients with a displaced femoral neck fracture . The study was part of a prospect i ve r and omised study comparing two different surgical procedures , internal fixation ( IF ) and total hip replacement ( THP ) . Setting : University hospital . Patients : A total of 110 patients , mean age 80 years with an acute displaced femoral neck fracture ( Garden III and IV ) . The inclusion criteria were age ≥70 , absence of severe cognitive dysfunction , independent living status and independent walking capability . Intervention : The patients were r and omised to IF or to a THR . Main outcome measurements : Health-related quality of life according to EQ-5D and SF-36 . Responsiveness measured by the ability of the EQ-5D and the SF-36 to detect clinical ly relevant differences in the study population according to an external criterion ( EC ) for outcome ( good or less good clinical outcome ) . Responsiveness was measured in terms of change scores , st and ardised effect size ( SES ) and st and ardised response mean ( SRM ) . Results : The rated prefracture EQ-5Dindex scores and SF-36 scores showed good correspondence with the scores of age-matched Swedish reference population s. The relationship between the EC and EQ-5Dindex score and the SF-36 global score showed significant differences in both comparisons ( p < 0.001 ) . The responsiveness expressed with the SES and SRM were large for both the EQ-5D ( 1.37 and 0.90 , respectively ) and for the SF-36 global score ( 0.89 and 0.82 , respectively ) . The correlation between the change scores for the SF-36 global score and the EQ-5D was 0.39 ( p < 0.001 ) . Conclusion : The results showed high responsiveness for both the EQ-5D and the SF-36 , indicating that both instruments are suitable for use as outcome measures in clinical trials in elderly hip fracture patients The study examined the association of nutritional status , obesity and physical activity ( PA ) with health-related quality of life ( HRQL ) in the elderly , and whether this relationship persists after controlling for confounders attributable to comorbidities , functional status and cognitive function . A total of 300 community-dwelling persons ( 177 women and 123 men ) between 66 and 79 years of age were r and omly chosen from all inhabitants of one district of the city of Lodz ( Pol and ) . HRQL was assessed with the Euroqol 5D question naire . PA was assessed by two question naires : the Seven Day Recall PA Question naire and the Stanford Usual Activity Question naire . Comorbidities , nutritional state ( Mini Nutritional Assessment question naire – MNA ) , physical disability , cognitive function and psychological state were also assessed . In bivariate relationships body mass index ( BMI ) , waist-to-hip ratio ( WHR ) and the percentage of body fat were negatively related to several HRQL scores both in women and men . Similarly , many HRQL scores were positively related to PA indices in both genders . In multivariate relationships , after adjustments for age , gender , smoking status , number of medications taken , comorbidities and geriatric physical and cognitive function , BMI predicted lower mobility while the percentage of body fat independently contributed to more frequent pain/discomfort and anxiety/depression problems . An adequate MNA added to a higher usual activity score , while a higher Stanford Moderate PA Index predicted better overall perceived health state . These results indicate that excess body fatness and sedentary lifestyle have , together with several functional and medical comorbidities , an independent contribution to inferior HRQL in communitydwelling older subjects . ZusammenfassungDie Untersuchung prüfte den Einfluss des Ernährungszust and es , des Übergewichts und der Bewegungsaktivität auf Gesundheit und Lebensqualität ( HRQL ) bei älteren Personen , und ob dieser Zusammenhang weiter besteht , wenn die Störungen eliminiert werden , die mit dem begleitend auftretenden Krankheiten , dem funktionellen Zust and und der Erkenntnisfunktionen verbunden sind . An der Untersuchung nahmen 300 durch Los ausgewählte ältere ( 177 weibliche und 123 männliche ) zu Hause lebende Einwohner der Stadt Lodz i m Alter von 66 bis 79 teil . Gesundheit und Lebensqualität wurden mittels Euroqol 5DFragebogen beurteilt . Die Bewegungsaktivität wurde aufgrund zweier Fragebögen bewertet : Dem siebentägigen Fragebogen über die Bewegungsaktivität ( SDPAR ) und dem Fragebogen über die gewöhnlichen Tätigkeiten ( Stanford Usual Activity Question naire ) . Der Ernährungszust and wurde gemäß der MNA-Skala ( Mini Nutritional Assessment ) eingeschätzt . Der Beurteilung unterlagen ebenfalls : begleitende Auftreten von Krankheiten , Behinderungen , die funktionelle Leistungsfähigkeit und der psychische Zust and der Gefragten . In der einfaktoriellen Analyse der Varianten ANOVA , BMI , waren die Kennziffer des Umfangs der Taille und Hüften ( WHR ) , und der prozentuale Gehalt an Fettgewebe entsprechend reziprok zu manchen Ergebnissen der Lebensqualität sowohl bei den Frauen als auch bei den Männern . Eine ähnlich große Zahl von Ergebnissen dieser Lebensqualität wies eine proportionale ( positive ) Abhängigkeit von den Kennzahlen der physischen Aktivität für beide Geschlechter aus . In der multifaktoriellen Analyse , unter Berücksichtigung von Alter , Geschlecht , Rauchen , der Menge von eingenommenen Arzneimitteln , sowie der psychischen und körperlichen Aktivität , beeinträchtigte der BMI die Mobilität ( Beweglichkeit ) . Der prozentuelle Gehalt des Fettgewebes dagegen beeinflusste ein öfteres Schmerzempfinden/Discomfort bzw . Unruhe/Depression . Die entsprechende Beurteilung des Ernährungszust and es MNA verursachte ein höheres Aktivitätsergebnis als gewöhnlich , wobei der höhere ‘ Stanfort Moderater PA-Koeffizient ’ den besseren allgemeinen Gesundheitszust and bestimmte . Diese Ergebnisse bedeuten , dass das Übergewicht und die sitzende Lebensweise samt funktionell und medizinisch begleitenden Auftreten von Krankheiten einen unabhängigen Einfluss auf die Gesundheit und Lebensqualität der zu Hause lebenden älteren Personen haben Purpose : Design ated multidisciplinary rehabilitation units have been shown to provide several benefits for the frail older population . The aim of this research was to evaluate changes in strength , mobility , balance , endurance , frailty and quality of life ( QoL ) following a 6-week multidisciplinary inpatient rehabilitation programme . Method : This was a prospect i ve , observational study performed in a post-acute multidisciplinary geriatric inpatient rehabilitation service . A consecutive sample of heterogenous frail older adults ( n = 32 ) participated . Subjects were assessed on admission to the rehabilitation service ( T1 ) and following 6 weeks of rehabilitation ( T2 ) . A range of outcome measures were used to assess function and QoL : Berg Balance Scale ( BBS ) , Timed Up and Go ( TUG ) , 6-Minute Walk Test ( 6MWT ) , Barthel Index ( BI ) , EuroQol-Visual Analogue Scale ( EQ-VAS ) , Clinical Frailty Scale ( CFS ) , lower limb and grip dynamometry . Results : The majority were female ( n = 25 ) , the mean age was 82.9 years ( SD 6.35 ) . The median length of stay was 49 days . Patients improved significantly between T1 and T2 assessment s in the BBS ( p ≤ 0.0001 ) ; TUG ( p ≤ 0.0001 ) ; 6MWT ( p ≤ 0.0001 ) ; BI ( p ≤ 0.0001 ) ; EQ-VAS ( p = 0.002 ) ; CFS ( p ≤ 0.0001 ) ; and in some aspects of grip and lower limb strength . Conclusion : This study has demonstrated that positive outcomes occurred in a range of measures in an older , frail inpatient rehabilitation population . Implication s for Rehabilitation Elderly in patients undergoing rehabilitation programmes improve across a range of measures looking at impairment , activity , participation and quality of life . However , gains were modest and patients did not attain their baseline level of performance after a 6-week programme of inpatient rehabilitation . Using outcome measures in clinical rehabilitation practice can facilitate comparison between units and can form the basis for future research in this population Background . The economic evaluation of health interventions for older people is complicated by the difficulty in obtaining self-reports of quality of life from persons with cognitive impairments , physical impairments , or both . Objectives . Using the EQ-5D ( EuroQoL ) measures , to assess : ( 1 ) agreement between subjects and proxies on subject ’s quality of life ratings at different points in time ; ( 2 ) agreement between subjects and proxies on change of subject ’s quality of life ratings over time ; and ( 3 ) subject and proxy characteristics related to agreement . Research Design . Prospect i ve study of subjects visiting hospital emergency departments ( ED ) . Data were collected at enrollment in the ED and at follow-up , 1 and 4 months after the ED visit . Subjects . The study comprised 231 pairs of cognitively intact patients aged 65 years or older and their primary caregivers . Measures . Quality of life was measured using both components of the EQ-5D scale , the index score and the Visual Analogue Scale ( VAS ) . Demographic characteristics and health status ( physical and mental ) were measured for both subjects and proxies . Subjects and proxies were interviewed either in English or French . Results . There was low to moderate agreement between subjects and proxies at different points in time ( intraclass correlation coefficient [ ICC ] = 0.22 to 0.59 ) , and between subject and proxy change scores over time ( ICC = 0–0.50 ) , on both the index score and the VAS . Better agreement between subjects and proxies was found at the 4 months follow-up , when the subject was less depressed , and when the proxy ’s native language was English . Conclusions . Proxy EQ-5D responses , either for a specific point in time or for assessing change over time , may not be valid measures of self-reported quality of life among older medically-ill patients Quality of care can be measured by using either processes or outcomes . Each method has its strengths and limitations ( 1 ) . With the concurrence of the Assessing Care of Vulnerable Elders ( ACOVE ) Policy Advisory Committee [ 2 ] , we chose to assess the care of vulnerable elders by using processes rather than outcomes . We did so because 1 ) processes are a more efficient measure of quality ; 2 ) for most conditions there are insufficient information in the medical record and a paucity of vali date d models to adequately adjust outcomes for differences in case mix between providers ; and 3 ) ultimately , processes of care are amenable to direct action by providers . To be a valid measure of quality , a health care process must be strongly linked to an outcome that is important to patients . Ideally , high- quality published studies would link performance of all such processes to outcomes ; however , few health care processes are supported by high- quality evidence ( 3 ) . Even when a process is supported by strong evidence from r and omized clinical trials , the inclusion and exclusion criteria of the clinical trials leave the evidence directly applicable to only a narrow group of patients ( 4 , 5 ) . This is particularly true for vulnerable elders , who are typically excluded from clinical trials ( 6 ) . Therefore , as we developed the ACOVE quality indicators , we used expert opinion to interpret the available evidence for applicability to vulnerable elders . Our methods entailed a literature review and several levels of expert opinion ( Figure ) , which we explain in detail . Figure . Assessing Care of Vulnerable Elders ( ACOVE ) method for developing quality indicators for vulnerable elders . Methods Development of Draft Process Indicators For each ACOVE condition that we selected for quality improvement in vulnerable elders ( 2 ) , we identified a content expert , who worked as a team with another project member knowledgeable about systematic review s and quality indicator development . Together , the content expert and project member developed potential quality indicators from existing guidelines , review criteria , and expert opinion . Because practice guidelines and existing quality indicators are seldom referenced in the traditional scientific data bases , we used various search strategies to locate these material s. In addition to search ing MEDLINE , we search ed the following sources : CONQUEST 1.1 ( A Computerized Needs-Oriented Quality Measurement Evaluation System ) ( 7 ) ; DEMPAQ : A Project to Develop and Evaluate Methods to Promote Ambulatory Care Quality ( 8) ; Directory of Clinical Practice Guidelines ( 9 ) ; Guide to Clinical Preventive Services ( 10 ) ; HEDIS 3.0 : Health Plan Employer Data and Information Set ( 11 ) ; National Guideline Clearinghouse ( 12 ) ; National Library of Health Care Indicators ( 13 ) ; and The Medical Outcomes & Guidelines Source book ( 14 ) . We also h and search ed the tables of contents of all issues of The Journal of the American Medical Association and Medical Care published April through November 1998 for relevant practice guidelines and quality indicators . Furthermore , we requested practice guidelines and quality indicators from the following agencies and organizations : Administration on Aging ( AOA ) ; Agency for Health Care Policy and Research (AHCPR)now known as Agency for Healthcare Research and Quality ( AHRQ ) ; Centers for Disease Control and Prevention ( CDC ) ; Department of Health and Human Services ( DHHS ) ; Department of Veterans Affairs ; Foundation for Accountability ( FACCT ) ; Health Care Financing Administration ( HCFA ) ; HCFA/Connecticut Peer Review Organization ; Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) ; National Committee for Quality Assurance ( NCQA ) ; and National Institutes of Health ( NIH ) . By using the quality indicators identified through this process , as well as using expert opinion and existing guidelines , the content expert developed 20 to 30 preliminary quality indicators for further review . Potential indicators were constructed in an IFTHENBECAUSE format : IF refers to the clinical characteristics that describe persons eligible for the quality indicator ; THEN indicates the actual process that should or should not be performed ; and BECAUSE refers to the expected health impact if the indicator is performed . For example , IF a vulnerable elder has heart failure with an ejection fraction of 40 % or less , THEN an angiotensin-converting enzyme ( ACE ) inhibitor should be offered BECAUSE treatment with ACE inhibitors improves longevity . We circulated this initial set of potential quality indicators to other clinical experts for their review . On the basis of review ers ' comments , we narrowed down the initial set to the 10 to 25 most promising indicators for future development . Review of Scientific Literature Next , we assessed the published evidence supporting a link between the process specified in each quality indicator and patient outcomes . To do so , we performed a systematic review on each quality indicator by using the essence of the Cochrane Collaboration 's methods (15)except that we used a single review er to screen and assess studies . With the assistance of a reference librarian , we electronically search ed MEDLINE , EMBASE , The Cochrane Data base of Systematic Review s , HealthSTAR , Ageline , and other specialized data bases on a condition-specific basis by using keywords and free-text terms to identify potentially relevant studies . For most conditions , the search es were not restricted by language . The content expert review ed the retrieved citations by using a three-step process : First , the titles were review ed for possibly relevant studies ; the abstract s associated with the titles that passed the first round of screening were then review ed ; and , finally , the full articles of abstract s that passed the second round of screening were review ed . Abstract s and articles were not masked for review . To be accepted , titles and abstract s had to contain information indicating that the full article probably reported evidence on the potential relationship between the process in question and better outcomes in humans . We excluded animal studies , letters , review articles , and other articles that did not report original data . In review ing full articles , we gave priority to evidence from studies with the strongest design s that were relevant to the potential quality indicator being examined . In general , this meant that we chose r and omized clinical trials for questions about the efficacy or effectiveness of interventions and prospect i ve cohort studies to answer questions about risk or prognosis . We considered such evidence to be direct evidence , and we judged direct evidence in elderly persons to be the strongest level of evidence available . In the absence of direct evidence in elderly persons , we performed search es for direct evidence in other groups . Indirect evidence that from less rigorous design sin elderly or nonelderly persons was review ed if the available direct evidence was insufficient . When both direct evidence and indirect evidence were lacking , we included the statements of authoritative bodies ( for example , specialty societies , National Institutes of Health consensus development conferences , or Agency for Health Care Policy and Research practice guidelines ) . After review ing all of the relevant articles , the content expert prepared a monograph detailing each of the quality indicators and summaries of the evidence supporting them . This monograph was sent to one or more peer review ers , who were asked to assess the quality of the monograph according to the following guidelines : 1 ) Is the review complete in terms of both the proposed quality criteria and the evidence ? 2 ) Is the review fair ( that is , is the presentation of the evidence unbiased ) ? The authors subsequently revised the monographs on the basis of review ers ' comments in a manner analogous to the response to a critique of a journal article : Each comment was addressed in turn , and the author provided an appropriate revision or stated the reason why he or she believed that no revision was indicated . Expert Panels We convened two multidisciplinary groups , each composed of 12 clinical experts , to interpret the supporting evidence detailed in the monographs and to select quality indicators for further consideration . Each panel of experts considered a separate set of ACOVE conditions . Table 1 lists the members of the panels and the conditions they considered . Table 1 . ACOVE Expert Panels To assess the expert opinions of the panelists , we used a modified version of the R AND /UCLA Appropriateness Method ( 16 , 17 ) . In brief , the method entails two rounds of anonymous ratings on a riskbenefit scale ranging from 1 to 9 and a face-to-face group discussion between rounds . Each panelist has equal weight in determining the final ratings . The reproducibility of the R AND /UCLA Appropriateness Method is consistent with that of well-accepted diagnostic tests , such as the interpretation of coronary angiography and screening mammography ( 18 ) . It also has content , construct , and predictive validity ( 5 , 17 , 19 , 20 ) . In this application of the method , we sent each panelist the proposed quality indicators and the relevant condition-specific monographs . We asked the panelists to assess the validity of each proposed indicator on a scale of 1 to 9 , in which 1 was definitely not valid and 9 was definitely valid . We considered an indicator to be valid if 1 ) adequate scientific evidence or professional consensus supported a link between the process specified by the indicator and a health benefit to the patient ; 2 ) a physician or health plan with high rates of adherence to the indicator would be considered a higher- quality provider ; and 3 ) the physician or health plan influenced a majority of factors that determine adherence to the indicator ( such as smoking cessation ) . Each panelist was instructed to rate each potential quality indicator for validity and return the ratings to us before the face-to-face BACKGROUND Many older people living in care homes ( long term residential care or nursing homes ) are depressed . Exercise is a promising non-drug intervention for preventing and treating depression in this population . OBJECTIVE To evaluate the impact of a ' whole-home ' intervention , consisting of training for residential and nursing home staff backed up with a twice-weekly , physiotherapist-led exercise class on depressive symptoms in care home residents . DESIGN A cluster r and omised controlled trial with a cost-effectiveness analysis to compare ( 1 ) the prevalence of depression in intervention homes with that in control homes in all residents contributing data 12 months after homes were r and omised ( cross-sectional analysis ) ; ( 2 ) the number of depressive symptoms at 6 months between intervention and control homes in residents who were depressed at pre-r and omisation baseline assessment ( depressed cohort comparison ) ; and ( 3 ) the number of depressive symptoms at 12 months between intervention and control homes in all residents who were present at pre-r and omisation baseline assessment ( cohort comparison ) . SETTING Seventy-eight care homes in Coventry and Warwickshire and north-east London . PARTICIPANTS Care home residents aged ≥ 65 years . INTERVENTIONS Control intervention : Depression awareness training programme for care home staff . Active intervention : A ' whole-home ' exercise intervention , consisting of training for care home staff backed up with a twice-weekly , physiotherapist-led exercise group . MAIN OUTCOME MEASURES Geriatric Depression Scale-15 , proxy European Quality of Life-5 Dimensions ( EQ-5D ) , cost-effectiveness from an National Health Service perspective , peripheral fractures and death . RESULTS We recruited a total of 1054 participants . Cross-sectional analysis : We obtained 595 Geriatric Depression Scale-15 scores and 724 proxy EQ-5D scores . For the cohort analyses we obtained 765 baseline Geriatric Depression Scale-15 scores and 776 proxy EQ-5D scores . Of the 781 who we assessed prior to r and omisation , 765 provided a Geriatric Depression Scale-15 score . Of these 374 ( 49 % ) were depressed and constitute our depressed cohort . Re source -use and quality -adjusted life-year data , based on proxy EQ-5D , were available for 798 residents recruited prior to r and omisation . We delivered 3191 group exercise sessions with 31,705 person attendances and an average group size of 10 ( 5.3 study participants and 4.6 non- study participants ) . On average , our participants attended around half of the possible sessions . No serious adverse events occurred during the group exercise sessions . In the cross-sectional analysis the odds for being depressed were 0.76 [ 95 % confidence interval ( CI ) 0.53 to 1.09 ] lower in the intervention group at 12 months . The point estimates for benefit for both the cohort analysis ( 0.13 , 95 % CI -0.33 to 0.60 ) and depressed cohort ( 0.22 , 95 % CI -0.52 to 0.95 ) favoured the control intervention . There was no evidence of differences in fracture rates or mortality ( odds ratio 1.07 , 95 % CI 0.79 to 1.48 ) between the two groups . There was no evidence of differences in the other outcomes between the two groups . Economic analysis : The additional National Health Service cost of the OPERA intervention was £ 374 per participant ( 95 % CI -£655 to £ 1404 ) ; the mean difference in quality -adjusted life-year was -0.0014 ( 95 % CI -0.0728 to 0.0699 ) . The active intervention was thus dominated by the control intervention , which was more effective and less costly . CONCLUSION The results do not support the use of a whole-home physical activity and moderate-intensity exercise programme to reduce depression in care home residents . TRIAL REGISTRATION Current Controlled Trials IS RCT N43769277 . FUNDING This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 18 . See the Health Technology Assessment programme website for further project information Introduction : Chronic heart failure ( CHF ) limits exercise capacity which influences physical fitness and health-related quality of life ( HRQoL ) . Aim : The aim was to determine the effects on physical capacity and HRQoL of an exercise programme in elderly patients with CHF in primary care . Methods : An exercise intervention was conducted as a prospect i ve , longitudinal and controlled clinical study in primary care in elderly patients with CHF . Endurance exercise and resistance training were conducted as group-training at the primary care centre and as home training . Follow-up on physical capacity and HRQoL was done at 3 , 6 and 12 months . Results : Exercise significantly improved muscle endurance in the intervention group ( n = 29 , mean age 76.2 years ) compared to the control group ( n = 31 , mean age 74.4 years ) at all follow-ups except for shoulder flexion right at 12 months ( shoulder abduction p = 0.006 , p = 0.048 , p = 0.029 ; shoulder flexion right p = 0.002 , p = 0.032 , p = 0.585 ; shoulder flexion left p = 0.000 , p = 0.046 , p = 0.004 ) . Six minute walk test improved in the intervention group at 3 months ( p = 0.013 ) compared to the control group . HRQoL measured by EQ5D-VAS significantly improved in the intervention group at 3 and 12 months ( p = 0.016 and p = 0.034 ) and SF-36 , general health ( p = 0.048 ) and physical component scale ( p = 0.026 ) significantly improved at 3 months compared to the control group . Conclusion : This study shows that exercise conducted in groups in primary care and in the patients ' homes could be used in elderly patients with CHF . The combination of endurance exercise and resistance training has positive effects on physical capacity . However , the minor effects in HRQoL need further verification in a study with a larger study population BACKGROUND Malnutrition is prevalent in acute hospitals and malnourished patients have an increased risk of morbidity and mortality . Studies of malnutrition and quality of life ( QoL ) are generally limited by both the nutritional and QoL assessment methods employed . The present study aim ed to evaluate the relationship between malnutrition , as assessed using a range of nutritional assessment methods , and QoL , as measured by EuroQol-5D-3L and Short-Form (SF)-36 question naires . METHODS The study comprised a prospect i ve cross-sectional study of malnutrition and QoL in 149 in patients aged 65 - 99 years . Exclusion criteria were : terminal illness , active malignancy , lack of capacity to consent and severe communication difficulties . Spearman 's rank correlation coefficient was used to test the association between QoL indices and nutritional markers . QoL scores for those scoring above and below thresholds for nutritional risk were compared . Regression models were created to identify nutritional indices contributing to the variability of QoL. RESULTS There were significant associations between QoL scores and the Mini Nutritional Assessment (MNA)-SF . Clear differences were evident between malnourished and well-nourished patients ( on the MNA-SF ) , those with low and normal arm muscle circumference and those with good and poor physical function . Regression analysis showed that nutritional scores and functional status made independent contributions to the prediction of QoL. The effect on food intake , mobility and psychological stress/acute disease also had a significant influence . CONCLUSIONS Malnutrition risk is linked to a poorer QoL in older people on admission to hospital . Functional status and eating-related factors are major influencers on QoL in this group . These findings reinforce the role of nutrition as a priority with respect to achieving improvements in Abstract Objective . The aim of the study was to assess the effect on prescription quality and quality of life after intervention with prescription review s and promotion of patient participation in primary care . Design . A r and omized controlled study with three groups : ( A ) controls , ( B ) prescription review sent to physician , and ( C ) as in B and with a current comprehensive medication record sent to the patient . Setting . The municipality of Örebro , Sweden ( 130 000 inhabitants ) . Intervention . The study focused on the easiest possible intervention to increase prescription quality and thereby increase quality of life . The intervention should be cost-efficient , focus on colleague-to-colleague advice , and be possible to perform in the primary health care centre without additional re sources such as a pharmacist . Subjects . 150 patients recently discharged from hospital . Inclusion criteria were : ≥ 75 years , ≥ five drugs and living in ordinary homes . Main outcome measures . Quality of life ( EQ-5D index , EQ VAS ) and quality of prescriptions . Results . Extreme polypharmacy was common and persistent in all three groups and this was accompanied by an unchanged frequency of drug-risk indicators . There was a low EQ-5D index and EQ VAS in all three groups throughout the study . No statistically significant differences were found anywhere between the groups . Conclusion . The intervention seems to have had no effect on quality of prescriptions or quality of life . This underlines the major challenge of finding new strategies for improving prescription quality to improve patient outcome measures such as quality of life and reduce the known risks of polypharmacy for the elderly Late-life depression is associated with disabled functioning and a poor quality of life ( QOL ) . The aim of this cross-sectional study was to find out whether the attendance of a day care centre ( DC ) was associated with QOL in community-dwelling older adults suffering from a depressive disorder without dementia . The study enrolled 149 depressed older adults aged 70 or older , who consecutively underwent a comprehensive geriatric assessment from April to July 2008 at the Geriatric Medicine Unit of the Fondazione Ospedale Maggiore Policlinico in Milan , Italy . QOL was evaluated by means of the European Quality of Life Visual Analogue Scale ( EuroQol VAS ) . DC attendance was quantified as number of days of attendance per week in the past month . Participants attending a DC at least once a week ( n = 17 ) had a higher mean EuroQol VAS score than non-attendants ( n = 132 ) ( mean ± SD 58.8 ± 19 vs. 45.3 ± 22.5 ; P = 0.019 ) . In multiple linear regression analysis a higher weekly attendance of DCs was related to a better quality of life according to the EuroQol VAS score ( unst and ardized coefficient 3.048 , 95 % CI 0.063–6.033 , P = 0.045 ) after correction for age , sex , balance and gait abilities , comorbidity , pharmacotherapy , living alone , and severity of depression . Therefore , in older out patients suffering from a depressive disorder without dementia the attendance of a DC was an independent correlate of the QOL . A r and omized controlled longitudinal study will be necessary to determine whether attending a DC is really effective on the QOL in the management of late-life depression Objective : To establish reliable st and ards for surgical application to elderly patients 75 years old or older with gastric or colorectal cancer with special reference to the postoperative recovery of activities of daily living ( ADL ) and quality of life ( QOL ) . Summary Background Data : ADL and QOL are important outcomes of surgery for the elderly . However , there has been only limited evidence on the natural course of recovery of functional independence . Methods : Two hundred twenty-three patients 75 years old or older with gastric or colorectal cancer were prospect ively examined . Physical conditions , ADL , and QOL were evaluated preoperatively and at the first , third , and sixth postoperative month . Results : The mortality and morbidity rates were 0.4 % and 28 % , respectively . Twenty-four percent of patients showed a decrease in ADL at 1 month postoperatively , but most patients recovered from this transient reduction , with only 3 % showing a decline at the sixth postoperative month ( 6POM ) . ADL of these patients was likely to decrease after discharge from the hospital . QOL of the patients showed a recovery to an extent equal to or better than their average preoperative scores . Conclusions : Of the patients 75 years old or older who underwent elective surgery for gastric or colorectal cancer , only a few showed a protracted decline in ADL and most exhibited better QOL after surgery . This indicates that surgical treatment should be considered , whenever needed , for elderly patients 75 years old or older with gastric or colorectal cancer . Estimation of Physical Ability and Surgical Stress is useful for predicting postoperative declines in ADL and protracted disability ; this could aid in establishing a directed rehabilitation program for preventing protracted disability in elderly patients Objectives Studies on implementation techniques that focus on nutrition in the setting of elderly care are scarce . The aims of this study were to compare two implementation strategies i.e. , external facilitation ( EF ) and educational outreach visits ( EOVs ) , in order to introduce nutritional guidelines ( e.g. screening , food quality and mealtime ambience ) , into a nursing home ( NH ) setting and to evaluate the clinical outcomes . Design A controlled study with baseline and follow-up measurements . Setting Four NHs . Participants A total of 101 NH residents . InterventionThe EF was a one-year , multifaceted intervention that included support , guidance , practice audits , and feedback that were provided to two NHs . The EOVs performed at the other NHs consisted of one session of three hours of lectures about the guidelines . Both interventions targeted a team of the unit manager , the head nurse , and 5–10 of the care staff . Measurements The outcomes were nutritional status ( Mini Nutritional Assessment -Short Form , MNA-SF ) , body mass index ( BMI ) , functional ability ( Barthel Index , BI ) , cognitive function ( Short Portable Mental Status Question naire , SPMSQ , performed in a subgroup of communicative NH residents ) , health-related quality of life ( EQ-5D ) , and the levels of certain biochemical markers like for example vitamin D , albumin and insulin-like growth factor 1 . Results After a median of 18 months , nutritional parameters ( MNA-SF and BMI ) remained unchanged in both groups . While there were no differences in most outcomes between the two groups , the cognitive ability of those in the EOV group deteriorated more than in individuals in the EF group ( p=0.008 ) . Multiple linear regression analyses indicated that the intervention group assignment ( EF ) was independently from other potentially related factors associated with less cognitive decline . Conclusion An extended model of implementation of nutritional guidelines , including guidance and feedback to NH staff , did not affect nutritional status but may be associated with a delayed cognitive decline in communicative NH residents AIMS To compare the quality of life ( QoL ) of those in atrial fibrillation ( AF ) aged 75 years and over with that of the general population , to explore what factors affect the QoL of those with AF , and to assess the sensitivity of the EuroQol ( EQ-5D ) and Short-Form 12 ( SF-12 ) generic health question naires in detecting differences in health status in those with AF in this age group . METHODS AND RESULTS The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a r and omization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged ( BAFTA ) study , a primary care based trial of stroke prevention . Patients self-completed the EQ-5D and SF-12 question naires , and a simple measure of disability ( Rankin ) . Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity . Quality -of-life outcomes were compared with general population sample s of the same age . On multiple regression , female gender , greater medication use , and disability were independently associated with lower QoL scores in AF . Those in AF with a Rankin score ≥2 had lower QoL scores , while those with a Rankin score < 2 had higher scores than the general population . Increasing co-morbidity was associated with reduced QoL scores , with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations , and the SF-12 Mental Component Score showing less sensitivity . CONCLUSION In the absence of co-morbidity , chronic AF has little impact on generic QoL in an elderly non-acutely ill population BACKGROUND If an association between a decline in physical performance and subjective QOL is confirmed , the SPPB could be used as a predictor for declining QOL in older people . OBJECTIVE This study aim ed to eluci date the association between the short physical performance battery ( SPPB ) and QOL ( EQ-5D ) to determine the utility of the SPPB as a predictor of declining QOL . METHODS The SPPB and the EQ-5D test were performed with a r and om sample of participants nested in the Korean Longitudinal Study of Aging ( KLoSA ) panel . Comparisons of the adjusted mean scores on the EQ-5D index between normal and abnormal SPPB groups were performed . We selected the quartiles of the EQ-5D index variables for the analysis . The association between the EQ-5D index and SPPB abnormality was examined using multinomial logistic regression analysis . Additionally , the associations between gait speed and chair st and time and the EQ-5D index were examined using the same analysis . RESULTS Four hundred and twenty-two subjects were included in the analysis . The adjusted means for the EQ-5D index were significantly lower when the SPPB score was abnormal ( p=0.022 for men , p=0.047 for women ) . An abnormal SPPB score was significantly associated with the lowest quartile of EQ-5D index score ( adjusted OR 3.54 in the lowest quartile for men ; adjusted OR 2.50 and 3.37 in the lowest and second quartiles for women ) . Gait speed was significantly associated with the EQ-5D index for participants of both sexes , but st and up time was associated with the EQ-5D index only for men . CONCLUSIONS An abnormal SPPB score was associated with lower QOL . Thus , the SPPB has the potential to be used as an early predictor of declining QOL in clinical setting s and epidemiological studies Objective : Falls , loss of health-related quality of life and physical capacity , reduced participation in activities of daily living , and increased fear of falling are all potential outcomes for older adults discharged from hospital . A low-cost video based exercise programme may address this . Design : This study was a r and omized controlled trial with blinded outcomes assessment and a six-month follow-up . Subjects and setting : Participants were older adults ( > 65 years ) using a mobility aid discharged from a tertiary hospital in Brisbane , Australia , without referral for community-based rehabilitation services . Intervention : A digital video disk-based programme encompassing six exercise types each with six levels of difficulty . A home visit from a project physiotherapist was conducted to ensure patient safety . Control group patients received usual care . Main measures : Falls , health-related quality of life , participation in activities of daily living , physical capacity and fear of falling . Results : Study participants ( n = 53 , 19 intervention , 34 control ) experienced decreasing health-related quality of life , several falls ( 72 ) , and lower levels of participation in activities of daily living over the six-month follow-up . The intervention group did not differ significantly from the control group in terms of the outcomes examined , though a non-significant reduction in the rate of falls was observed . Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter . Conclusions : The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated |
11,197 | 22,271,210 | Conclusions Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission , 1-year survival , and alleviation of radiochemotherapy-related side effects | Background Recently , melatonin has been associated with cancer both in vitro and in vivo .
However , the value of melatonin in the treatment of cancer remains disputable .
Hence , we performed a systematic review of r and omized controlled trials ( RCTs ) of melatonin in solid tumor cancer patients and observed its effect on tumor remission , 1-year survival , and side effects due to radiochemotherapy . | Several experimental studies have shown that melatonin has an oncostatic action , either by stimulating host antitumor immune defenses or by directly inhibiting the growth of some cancer histotypes , including melanoma . Our previous clinical studies demonstrated that melatonin may induce stabilization of the disease in untreatable metastatic solid tumor patients , and these results have been confirmed by others , at least in patients with metastatic melanoma . On the contrary , at present there are no data related to the possible efficacy of melatonin as an adjuvant endocrine therapy . This study was performed to investigate the impact of melatonin therapy on the disease-free survival ( DFS ) in melanoma patients surgically treated for regional node recurrence . The study included 30 node-relapsed melanoma patients , who were r and omized to receive no treatment or adjuvant therapy of melatonin ( 20 mg/day orally in the evening ) every day until disease progression . After a median follow up of 31 months , the percent of DFS was significantly higher in melatonin-treated individuals than in controls . The DFS curve was also significantly longer in melatonin group than in controls . No melatonin-related toxicity was observed . This preliminary study suggests that an adjuvant endocrine therapy with melatonin may be effective in preventing disease progression in node-relapsed melanoma patients Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 ( IL-2 ) is not co-administration of another cytokine , but the association with immunomodulating neurohormones , in an attempt to reproduce the physiological links between psychoendocrine and immune systems , which play a fundamental role in the regulation of the immune responses . In particular , the association with the pineal neurohormone melatonin ( MLT ) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone . To confirm these preliminary results , a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma . The study included 80 consecutive patients , who were r and omised to be treated with IL-2 alone subcutaneously ( 3 million IU day-1 at 8.00 p.m. 6 days a week for 4 weeks ) or IL-2 plus MLT ( 40 mg day-1 orally at 8.00 p.m. every day starting 7 days before IL-2 ) . A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone . A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone . Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone ( 11/41 vs 1/39 , P < 0.001 ) . The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group ( 19/41 vs 6/39 , P < 0.05 ) . Finally , the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone ; on the contrary , the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone . The treatment was well tolerated in both groups of patients . This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy BACKGROUND Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gl and , which , in turn , could increase the release of estrogen by the ovaries . This study investigated whether such exposure is associated with an increased risk of breast cancer in women . METHODS Case patients ( n = 813 ) , aged 20 - 74 years , were diagnosed from November 1992 through March 1995 ; control subjects ( n = 793 ) were identified by r and om-digit dialing and were frequency matched according to 5-year age groups . An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history . Odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated by use of conditional logistic regression , with adjustment for other potential risk factors . RESULTS Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest ( OR = 1.14 for each night per week ; 95 % CI = 1.01 to 1.28 ) . Risk did not increase with interrupted sleep accompanied by turning on a light . There was an indication of increased risk among subjects with the brightest bedrooms . Graveyard shiftwork was associated with increased breast cancer risk ( OR = 1.6 ; 95 % CI = 1.0 to 2.5 ) , with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork ( P = .02 , Wald chi-squared test ) . CONCLUSION The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer Hypotension is a frequent side-effect of cancer biotherapies with cytokines . Cytokine-induced hypotension would mainly depend on the stimulation of nitric oxide ( NO ) production , which represents the most effective endogenous vasodilator . Moreover , it has been proven that both biological activity and toxicity of cytokines are influenced by the psychoneuroendocrine system , in particular by the pineal hormone melatonin . To investigate the possible modulatory effect of melatonin on cytokine cardiovascular toxicity , we evaluated the influence of a concomitant melatonin administration on interleukin-2(IL-2)- and tumour-necrosis-factor-α(TNF)-induced hypotension in advanced cancer patients . The study included 116 patients with advanced solid tumour , for whom no effective st and ard anticancer therapy was available , who underwent cancer biotherapy with IL-2 ( 3 × 106 IU/day s.c . every day , 6 days/week for 4 weeks ) or with TNF ( 0.75 mg/day i.v . for 5 days ) as compassionate treatment for their disease . Patients were r and omized to be treated with or without a concomitant melatonin administration ( 40 mg/day orally in the evening , starting 7 days prior to cytokine injection ) . The occurrence of hypotension was significantly less frequent in patients concomitantly treated by melatonin than in those who received the cytokine alone , during either IL-2 or TNF immunotherapy ( IL-2 : 11/45 versus 2/46,P<0.05 ; TNF : 10/23 versus 1/12,P<0.01 ) . This study shows that melatonin may prevent hypotension occurring during cancer immunotherapy with IL-2 or TNF . Since the pineal hormone has appeared to inhibit the activity of NO synthase from the endothelial cells , we suggest that melatonin may prevent cytokine-induced hypotension by inhibiting NO production , which plays an essential role in inducing hypotension during IL-2 and TNF biotherapies Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage . In addition , melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production . On this basis , we have performed a r and omized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients ( NSCLC ) with poor clinical status . The study included 70 consecutive advanced NSCLC patients who were r and omized to receive chemotherapy alone with cisplatin ( 20 mg/m2/day i.v . for 3 days ) and etoposide ( 100 mg/m2/day i.v . for 3 days ) or chemotherapy plus melatonin ( 20 mg/day orally in the evening ) . Cycles were repeated at 21-day intervals . Clinical response and toxicity were evaluated according to World Health Organization criteria . A complete response ( CR ) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone . Partial response ( PR ) occurred in 10/34 and in 6/36 patients treated with or without melatonin , respectively . Thus , the tumor response rate was higher in patients receiving melatonin ( 11/34 vs. 6/35 ) , without , however , statistically significant differences . The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone ( 15/34 vs. 7/36 , P < 0.05 ) . Finally , chemotherapy was well tolerated in patients receiving melatonin , and in particular the frequency of myelosuppression , neuropathy , and cachexia was significantly lower in the melatonin group . This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy , mainly in terms of survival time , and reduce chemotherapeutic toxicity in advanced NSCLC , at least in patients in poor clinical condition Experimental data have suggested that the pineal hormone melatonin ( MLT ) may counteract chemotherapy-induced myelosuppression and immunosuppression . In addition , MLT has been shown to inhibit the production of free radicals , which play a part in mediating the toxicity of chemotherapy . A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity . The study involved 80 patients with metastatic solid tumors who were in poor clinical condition ( lung cancer : 35 ; breast cancer : 31 ; gastrointestinal tract tumors : 14 ) . Lung cancer patients were treated with cisplatin and etoposide , breast cancer patients with mitoxantrone , and gastrointestinal tract tumor patients with 5-fluorouracil plus folates . Patients were r and omised to receive chemotherapy alone or chemotherapy plus MLT ( 20 mg/day p.o . in the evening ) . Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT . Malaise and asthenia were also significantly less frequent in patients receiving MLT . Finally , stomatitis and neuropathy were less frequent in the MLT group , albeit without statistically significant differences . Alopecia and vomiting were not influenced by MLT . This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects , particularly myelosuppression and neuropathy . Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations At present , there is no effective medical therapy in metastatic nonsmall cell ( NSC ) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin . Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin ( MLT ) , a r and omized study was design ed to evaluate the influence of an MLT treatment ( 10 mg/day orally at 7.00 p.m. ) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients , who did not respond to a first-line chemotherapy containing cisplatin . The study includes 63 consecutive metastatic NSC lung cancer patients , who were r and omized to receive MLT ( n = 31 ) or supportive care alone ( n = 32 ) . The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care . No drug-related toxicity was seen in patients treated with MLT , who , on the contrary , showed a significant improvement in performance status . This r and omized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin , for whom no other effective therapy is available up to now Several experiments have demonstrated that pineal gl and plays a physiological anticancer role . Melatonin ( MLT ) , its most investigated hormone , is a natural anticancer agent . However , MLT would not be the only endocrine molecule responsible for the anticancer property of the pineal gl and . In fact , another pineal indole hormone , the 5-methoxytryptamine ( 5-MTT ) , has appeared to exert in vitro an antitumour activity superior to that of MLT itself . Previous studies have already shown the therapeutic anticancer action of MLT in association with chemotherapy also in human neoplasms . This study was performed to evaluate the influence of 5-MTT at physiological doses ( 1 mg/day orally during light phase ) on the efficacy of chemotherapy with cisplatin plus etoposide in advanced non-small cell lung cancer patients with respect to that obtained in patients treated by chemotherapy alone or chemotherapy plus pharmacological doses of MLT ( 20 mg/day orally during the dark phase of the day ) . The study included 100 patients , who were r and omised to receive chemotherapy alone or in association with MLT or 5-MTT . The overall response rate achieved in both patients concomitantly treated with MLT or 5-MTT was significantly higher with respect to that obtained in patients treated with chemotherapy alone . Moreover , both MLT and 5-MTT significantly reduced some chemotherapy-related toxicities , namely thrombocytopenia and neurotoxicity . This preliminary study shows that less known pineal hormone 5-MTT may exert at low doses the same anticancer therapeutic effect in association with chemotherapy , which may be obtained by pharmacological doses of the most investigated pineal hormone MLT The pineal hormone melatonin ( MLT ) has been shown to influence many biological functions , including immune response , cancer growth and brain neurotransmitter contents . On the basis of its biological properties , a study was started to evaluate the influence of MLT on IL-2 immunotherapy toxicity . The study was carried out in metastatic renal cancer patients . Thirty-three 5-day courses of IL-2 at a daily dose of 3 x 10(6 ) Cetus U/m2 were r and omized to consist of IL-2 alone or IL-2 plus MLT ( 10 mg/day orally at 8.00 p.m. ) . The frequency of episodes of severe hypotension was significantly greater during IL-2 alone than during IL-2 + MLT . Moreover , the depressive symptomatology occurred more frequently during IL-2 alone . No other toxicity , including capillary leak syndrome , vomiting and fever , were significantly influenced by the concomitant treatment with MLT . These preliminary results would suggest that the pineal hormone MLT may be successfully associated with IL-2 in the immunotherapy of human tumors Previous experimental studies have suggested the possibility to modulate the biological activity and toxicity of cytokines by immunomodulating neurohormones . In particular , the pineal hormone melatonin ( MLT ) has been proven to amplify the immune effects of IL-2 and to reduce its toxicity . On this basis , we decided to investigate the effect of MLT on biological activity and toxicity of another important antitumor cytokine , TNF . The study was performed in 14 metastatic solid tumor patients , for whom no effective st and ard antitumor therapy was available . Informed consent was previously obtained from each patient . Patients were r and omized to be treated with TNF or TNF plus MLT . Recombinant human TNF was given at a daily dose of 0.75 mg intravenously for 5 consecutive days . MLT was given orally at a daily dose of 40 mg , starting 7 days before TNF . Lymphocyte mean number observed at the end of TNF infusion was significantly higher in patients treated with TNF plus MLT than in those receiving TNF alone . On the contrary , no significant difference occurred in hemoglobin , platelet and neutrophil mean values . Asthenia and hypotension were significantly less frequent in patients treated with TNF plus MLT , whereas no difference occurred in the frequency of fever and chills . Even though limited to a small number of patients , this preliminary study would suggest the possibility to modulate TNF toxicity and biological activity by a concomitant treatment with the pineal hormone MLT The prognosis of brain glioblastoma is still very poor and the median survival time is generally less than 6 months . At present , no chemotherapy has appeared to influence its prognosis . On the other h and , recent advances in brain tumor biology have suggested that brain tumor growth is at least in part under a neuroendocrine control , mainly realized by opioid peptides and pineal substances . On this basis , we evaluated the influence of a concomitant administration of the pineal hormone melatonin ( MLT ) in patients with glioblastoma treated with radical or adjuvant radiotherapy ( RT ) . The study included 30 patients with glioblastoma , who were r and omized to receive RT alone ( 60 Gy ) or RT plus MLT ( 20 mg/daily orally ) until disease progression . Both the survival curve and the percent of survival at 1 year were significantly higher in patients treated with RT plus MLT than in those receiving RT alone ( 6/14 vs. 1/16 ) . Moreover , RT or steroid therapy-related toxicities were lower in patients concomitantly treated with MLT . This preliminary study suggests that a radioneuroendocrine approach with RT plus the pineal hormone MLT may prolong the survival time and improve the quality of life of patients affected by glioblastoma IL–2 immunotherapy has been proven to be effective in the treatment of metastatic renal cell cancer ( RCC ) . However , several drugs commonly used in the palliative therapy of cancer may potentially influence IL–2 efficacy , since the anticancer immunity has appeared to depend on complex interactions between immune system and psychoneuroimmunomodulation . In particular , experimental studies and preliminary clinical investigations have shown that the opioid substances , namely morphine , may suppress the anticancer immunity and the efficacy of IL–2 itself . In contrast , other neuroactive substances , in particular the pineal hormone melatonin ( MLT ) , have been proven to stimulate the immune response , including the anticancer immunity , and to abrogate opioid – induced immunosuppression . On this basis , a study was planned to evaluate the effect of a concomitant MLT administration on the efficacy of IL–2 immunotherapy in advanced cancer patients chronically treated with morphine for cancer – related pain . The study was carried out in 30 metastatic RCC patients under chronic therapy with morphine at oral doses ranging from 60 to 120 mg/day . Patients were r and omized to receive morphine alone or morphine plus MLT ( 20 mg/day orally in the evening ) . The immunotherapeutic cycle consisted of IL–2 subcutaneous administration at a dose of 6 million IU/day for 6 days/week for 4 consecutive weeks . In nonprogressing patients , a second cycle was planned after a 21–day rest period . The percent of partial responses achieved in patients treated with morphine alone was significantly lower than that observed in patients concomitantly treated with MLT ( 1/16 vs. 4/14 , p<0.05 ) . Moreover , the 3–year percent of survival was significantly higher in patients concomitantly treated with MLT ( p<0.01 ) . In contrast , no diminished analgesic efficacy of morphine occurred in patients concomitantly treated with MLT . This preliminary study seems to suggest that the negative influence of morphine therapy for cancer – related pain on the clinical efficacy of IL–2 cancer immunotherapy may be abrogated by the concomitant administration of the immunomodulating pineal neurohormone MLT |
11,198 | 31,050,690 | This meta- analysis reveals that s and blasting is superior over machined surface in implant failure but not in marginal bone level in healthy subjects . | INTRODUCTION S and blasting is one of the oldest implant surface modifications to enhance osseointegration .
Regarding its superiority over machined surface controversies still exist .
Our objective was to compare implant failures ( IF ) and marginal bone level ( MBL ) changes between s and blasted and machined dental implants by a meta- analysis utilizing the available data . | This paper describes the 5-year results of a comparative study between Astra Tech and Brånemark system implants . The aim was to compare the systems primarily with regard to bone level changes , and also with regard to other variables of interest . Sixty-six patients with edentulous jaws were included in the study . R and omisation schedules were used to allocate the patients to the two implant systems . 184 Astra Tech implants with a titanium-blasted surface and 187 Brånemark implants with a turned surface were used . The implants were inserted with a two-stage technique and the insertion followed the routines for the respective implant system . All patients were provided with full-arch fixed bridges . All patients were followed up with clinical and radiographic examinations from fixture insertion to the 5-year follow-up . The total mean bone level change in the upper jaw between fixture insertion and the 5-year examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the Brånemark implants . The corresponding values for the lower jaw were -1.06+/-0.19 for Astra and -1.38+/-0.17 for Brånemark . The major postoperative changes of the marginal bone level took place between fixture insertion and baseline . During this period , there was also a different pattern of bone remodelling between the implant systems . Between baseline ( prosthesis connection ) and the 5-year examination , the marginal bone level changes were small , with no difference between the implant systems . The implant stability was examined with the supraconstructions removed . At the 5-year examination , the survival rate for Astra Tech implants was 98.4 % and for the Brånemark implants it was 94.6 % . The difference was not statistically significant PURPOSE To compare implants with machined vs roughened surfaces placed flapless in totally edentulous jaws and immediately restored with metal-resin screw-retained cross-arch prostheses . M and ibles were rehabilitated with two implants ( Fixed-on-2 or Fo2 ) and maxillae with three implants ( Fixed-on-3 or Fo3 ) . MATERIAL S AND METHODS Forty edentulous or to be rendered edentulous patients ( 20 in the m and ible and 20 in the maxilla ) were r and omised to the machined group ( 20 patients : 10 m and ibles and 10 maxillae ) and to the roughened group ( 20 patients : 10 m and ibles and 10 maxillae ) according to a parallel group design . To be immediately loaded implants had to be inserted with a minimum torque of 60 Ncm . Outcome measures were prosthesis and implant failures , complications and peri-implant marginal bone level changes evaluated up to 1 year post-loading . RESULTS Flaps were raised in four patients from the machined group . Four prostheses on machined implants and three on roughened implants were delayed for loading because a sufficient insertion torque was not obtained . There were no dropouts 1 year after loading . Two maxillary machined implants were lost in two patients ( difference in proportions = 0.10 ; 95 % CI = -0.03 to 0.23 ; P ( Fisher 's exact test ) = 0.487 ) ; one maxillary Fo3 prosthesis on machined implants and one m and ibular Fo2 prosthesis on roughened implants had to be remade ( difference in proportions = 0 ; 95 % CI = -0.14 to 0.14 ; P ( Fisher 's exact test ) = 1.000 ) . Five patients with machined implants had six complications vs seven patients who had eight complications at roughened implants ( difference in proportions = -0.10 ; 95 % CI = -0.38 to 0.18 ; P ( Fisher 's exact test ) = 0.731 ) . There were no statistically significant differences for implant failures , prosthetic failures or complications between groups . There were no statistically significant differences for marginal peri-implant bone levels between the two groups ( estimate of the difference = -0.06 mm ; 95 % CI = -0.23 to 0.10 ; P ( ANCOVA ) = 0.445 ) , with both groups losing marginal bone in a statistically significant way ( 0.35 ± 0.23 mm for machined and 0.42 ± 0.27 mm for roughened surface ) . CONCLUSIONS These preliminary results suggest that immediately loaded cross-arch prostheses can be supported by only two m and ibular or three maxillary dental implants at least up to 1 year post-loading , independently of the type of implant surface used . Longer follow-ups are needed to underst and whether one of the two-implant surfaces is preferable OBJECTIVE This report is a 20-year follow-up of a r and omized controlled clinical trial evaluating the potential long-term effect of a modified implant surface on the preservation of the peri-implant marginal bone level . MATERIAL & METHODS In each of 51 patients and for each fixed partial denture ( FPD ) , by r and omization at least one implant installed had a non-modified turned surface and one a modified and roughened surface ( TiOblast ® ) . Clinical and radiological examinations were performed at various follow-up intervals . Primary outcome variables were peri-implant marginal bone level change from time of loading and proportion of implants with no bone loss at 20 years . Multilevel analysis followed by nonparametric and Pearson 's Chi-Square tests were applied for statistical analysis . RESULTS At the 20-year follow-up , 25 patients carrying 64 implants were available for evaluation . Turned and TiOblast implants presented with a mean bone level change from the time of FDP delivery amounting to -0.41 mm ( 95 % CI -0.84/0.02 ) and -0.83 mm ( 95 % CI -1.38/-0.28 ) respectively ( inter-group comparison p > .05 ) . 47 % of the Turned and 34 % TiOblast implants ( p > .05 ) showed no bone loss . All but one of these implants were free of bacterial plaque and inflammation as well as presented with probing pocket depths ≤5 mm at both the 5- and 20-year follow-up examinations . CONCLUSION It is suggested that a moderate increase of implant surface roughness has no beneficial effect on long-term preservation of the peri-implant marginal bone level 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 The aim of this study was to evaluate the change in marginal bone level radiographically around two different implant systems after 7 years of use . MATERIAL AND METHODS Twenty fully edentulous patients were included in the study and r and omly assigned to two treatment groups of machined surface implants ( Brånemark , n = 40 ) and rough-surface implants ( Xive , n = 40 ) . The implants were early loaded with individual bar-retained overdentures . All patients were treated by the same surgeon and the same prosthodontist . Clinical and radiographic examinations were conducted at the time of implant loading ( baseline ) and annually for up to 7 years of use . Measurements to the nearest 0.1 mm were taken at the mesial and distal site , and the average values were calculated for each implant . A three-level mixed-effect analysis of covariance ( ANOVA ) was used to test the significance of the mean marginal bone change in the two implant groups . RESULTS The study population consisted of 15 women ( 75 % ) and five men ( 25 % ) with an average age of 61.6 years . A total of 79 of 80 implants integrated successfully . n = 1 Brånemark implant failed after 3 weeks . There was a significant difference ( P < 0.001 ) between the two implant systems at the baseline measurements ( 0.14 mm Brånemark vs. 0.39 mm Xive ) and a highly significant difference for the annual bone loss ( 0.07 mm [ Brånemark ] vs. 0.18 mm [ Xive ] , P < 0.001 ) . CONCLUSION Both the implant systems are clinical ly satisfying . Nevertheless , the Brånemark group showed a better radiological performance than the Xive group BACKGROUND Dental implants with moderately rough surfaces are commonly used in the treatment of edentulous patients . However , long-term data on survival rates and marginal bone conditions are lacking . PURPOSE This prospect i ve study evaluated the cumulative survival rate of the TiOblast implant ( Astra Tech AB , Mölndal , Sweden ) after 10 years of prosthetic loading . MATERIAL S AND METHODS A total of 199 TiOblast implants were placed in 36 consecutive edentulous patients ( 23 males and 13 females ) . All patients were treated at one clinic and by the same team . The patients were edentulous in either the maxilla ( n = 16 ) or the m and ible ( n = 20 ) . The average age of the patients at the start of the trial was 64 years ( range , 59 - 82 years ) . Of the 199 implants inserted 108 were in the m and ible and 91 were in the maxilla . Clinical evaluations were undertaken after completion of the prosthetic superstructure ( baseline ) and after 6 months , 1 year , 3 years , 5 years , 7 years , and 10 years . Mean marginal bone level was evaluated for the first 100 placed implants for up to 7 years . RESULTS Six implants failed during the study ( 3 in the m and ible and 3 in the maxilla ) . All failures occurred within the first year , giving a cumulative survival rate of 96.9 % ( 96.6 % in the maxilla and 97.2 % in the m and ible ) after 10 years of follow-up . The survival rate for the superstructures was 100 % . The mean marginal bone level in the measured sample was 0.2 mm ( st and ard deviation [ SD ] , 0.31 ) below the reference point at baseline , 0.28 mm ( SD , 0.20 ) and 1.27 mm ( SD , 1.15 ) below the same point 7 years later ( mean , 0.15 mm per year ) . CONCLUSION This study showed that titanium dioxide-blasted implants offer predictable long-term results as supports for fixed prostheses in both the maxilla and m and ible BACKGROUND Step-wise reduction in loading protocol s is necessary to evaluate early loading of implants with m and ibular overdentures . PURPOSE To compare the success rates of two different dental implant systems following conventional or early loading protocol s in patients being rehabilitated with m and ibular overdentures . MATERIAL S AND METHODS Forty-eight edentulous participants were r and omly allocated to two different implant systems : one with a machined titanium implant surface ( Sterioss , Nobel Biocare , Yorba Linda , California , USA ) and the other with a roughened titanium surface ( Southern Implants , Irene , South Africa ) . For each system , the participants were further divided into control groups , in whom m and ibular implant overdentures and their respective matrices were inserted following a st and ard 12-week healing period , and test groups , in whom a 6-week healing period was followed prior to identical loading . Two unsplinted implants to support implant overdentures were placed in the anterior m and ible of all participants , using a st and ardized one-stage surgical procedure . Mobility tests and marginal bone levels , as well as peri-implant parameters , were evaluated at each baseline and 52 and 104 weeks after surgery . RESULTS There was no statistically significant difference in the success rates of the two systems in either control or test groups . At the 2-year evaluation , a success rate was found of 87.5 % and 70.8 % for the control and test Sterioss groups , respectively , and 83.3 % and 100 % for the control and test Southern Implants groups were observed . For the Sterioss groups , eight implants were lost at an early stage : seven in the test group and one in the control group . For the Southern Implants control and test groups , no failures were seen at any time interval . There were no significant differences in marginal bone loss , Periotest values , and peri-implant parameters between implant systems or between any of the control or test groups . CONCLUSIONS Early loading , with step-wise reductions in loading protocol s , of unsplinted machined Sterioss and roughened Southern Implants fixtures with m and ibular overdentures is possible for up to 2 years BACKGROUND Evidence -based reports are needed to support the application of a one-stage surgical protocol for unsplinted implants supporting m and ibular overdentures . PURPOSE To examine the feasibility and success of using two different dental implant systems ( originally design ed for two-stage operative technique ) using a one-stage operative procedure in patients being rehabilitated with implant m and ibular overdentures . MATERIAL S AND METHODS The study sample involved 24 edentulous subjects ( aged 55 - 80 yr ) r and omly allocated to two different implant systems , one with a machined titanium implant surface ( Steri-Oss , Nobel Biocare , Göteborg , Sweden ) and the other with a roughened titanium surface ( Southern Implants , Ltd. , Irene , South Africa ) . Two unsplinted implants to support implant overdentures were placed in the anterior m and ible of all patients , using a st and ardized one-stage surgical and prosthodontic procedure . Primary stability and bicortical anchorage of the implants was m and atory before healing abutments were connected at the time of implant placement . Implant overdentures and their respective matrices were inserted following a st and ard 12-week healing period . Data relating to mobility tests , radiographs , and peri-implant parameters were documented at 12 , 16 , and 52 weeks after surgery . RESULTS A success rate of 95.8 % for the Steri-Oss and 100 % for the Southern Implants was found , without any statistically significant differences in the marginal bone loss . Significant changes in Periotest values were observed for both types between 12 and 52 weeks ( p < .001 ) . Minor changes were observed in the peri-implant parameters evaluated . CONCLUSIONS These preliminary findings show a successful application of this one-stage approach for unsplinted implants supporting m and ibular overdentures with Steri-Oss and Southern Implant Systems INTRODUCTION Many studies have dealt with the clinical outcome of oral implants , yet none applied a r and omized split-mouth design for a long-term follow-up of similar implant systems . AIM To evaluate two oral implant systems with different surface characteristics in a r and omized split-mouth design and to radiologically analyse peri-implant bone level and density over an up to 16-year period . MATERIAL S AND METHODS The study comprised clinical and radiographic records of 18 partially edentulous patients treated with both implant types r and omly placed in either left or right jaw sides . Outcome was evaluated over time . RESULTS Clinical and radiographic parameters showed no significant differences over time for both systems . Ten years after implant placement , a significantly increasing peri-implant bone density was noted , while Periotest values were found to be significantly decreasing . Fifteen years after implant loading , mean bone loss was 0.02 mm ( range -1.15 to 1.51 ; SD 0.45 ) for Astra Tech ® implants ( n=24 ) and 0.31 mm ( range -0.98 to 2.31 ; SD 0.69 ) for Brånemark ® implants ( n=23 ) . CONCLUSIONS The study failed to demonstrate significant differences in the outcome of the peri-implant bone for two implant systems with different surface characteristics . The marginal bone level around oral implants changed < 0.5 mm after 15 years of loading In 50 partially edentulous patients , 133 ( 48 maxillary ; 85 m and ibular ) Astra Tech dental implants of 2 different surface textures ( machined ; TiO-blasted ) were alternately installed , supporting 52 fixed partial dentures ( FPDs ) . Before abutment connection 2 machined implants ( 1 m and ibular ; 1 maxillary ) were found to be non-osseointegrated and were replaced . Another implant could not be restored due to a technical complication . Two FPDs were remade because of technical complications , both because of abutment fractures . Thus , after 2 years in function , the cumulative survival rates were 97.7 % and 95.7 % for implants and prostheses , respectively . There was no statistically significant difference in survival rate between the 2 types of implants , 100 % ( TiO-blasted ) vs 95.3 % ( machined ) , P = 0.24 . After 2 years in function , when both jaw and type of implants were combined , the mean ( SD ) marginal bone loss was 0.24 ( 0.69 ) mm . No statistically significant difference in bone loss was found between the 2 types of implant after 2 years of loading , 0.04 ( 0.82 ) mm , P > 0.30 PURPOSE To compare the effectiveness of immediately loaded total prostheses supported by implants with a roughened surface versus implants with a machined/turned surface . MATERIAL S AND METHODS Fifty edentulous or to-be-rendered edentulous patients requiring an implant-supported cross-arch prosthesis , were r and omised either to receive four to eight implants with a roughened surface ( 25 patients ) or with a machined/turned surface ( 25 patients ) . Provisional metal-reinforced acrylic prostheses were delivered 48 h after implant placement . Provisional prostheses were replaced after 4 months , by definitive screw-retained metal-resin cross-arch restorations . Outcome measures were prosthesis and implant failures , any complications and peri-implant marginal bone level changes . Patients were followed 1 year after loading . RESULTS One year after loading no patient dropped out . No prosthesis failed , but two machined implants were found to be mobile at definitive impression taking in 1 patient ( Fisher 's exact test : P = 0.312 ; difference in proportions = 4 % ; 95 % Cl : -10 to 18 ) . No complications occurred . Both groups presented a significant peri-implant marginal bone loss at 1 year after loading ( P < 0.0001 ) , -0.64 ± 0.20 mm for rough implants and -0.68 ± 0.23 mm for turned implants , respectively , with no statistically significant differences between the two groups ( P = 0.482 ; mean difference = 0.04 mm ; 95 % Cl : -0.17 to 0.25 ) . CONCLUSIONS Up to 1 year after immediate loading , both implant surfaces provided good and similar results , however , the only two implants which failed early in the same patient had a machined surface . These preliminary results must be confirmed by larger trials with longer follow-ups PURPOSE The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period . MATERIAL S AND METHODS A total of 133 implants ( Astra Tech Dental Implants ; Astra Tech AB , Mölndal , Sweden ) were placed in 50 patients at 6 centers in 4 Sc and inavian countries . Forty-eight implants were installed in the maxilla and 85 implants in the m and ible . A r and omization and a stratification were done , so that each fixed partial prosthesis was supported by at least 1 machined and 1 TiO(2)-blasted implant . The implant-supported fixed partial prostheses ( ISFPP ) were fabricated within 2 months after postoperative healing . A total of 52 ISFPP ( 17 maxillary , 35 m and ibular ) were inserted . The patients were clinical ly examined once a year for 5 years . At the annual follow-up , biological as well as technical complications were recorded . RESULTS Of the 133 implants placed , 3 were reported as failed after 5 years of follow-up , result ing in an overall cumulative survival rate of 97.6 % . The cumulative implant survival rates were 100 % for the TiO(2)-blasted implants and 95.1 % for the machined implants . No significant difference in survival was , however , found between the machined and TiO(2)-blasted implants after 5 years . The mean marginal bone loss in the maxilla was 0.21 + /- 0.83 mm ( SD ) for the machined implants and 0.51 + /- 1.11 mm ( SD ) for the TiO(2)-blasted implants during the 5-year observation period . In the m and ible , the mean marginal loss was 0.22 + /- 1.13 mm for the machined implants and 0.52 + /- 1.07 mm for the TiO(2)-blasted implants from baseline to the 5-year examination . No significant difference in marginal bone loss between the 2 surface groups was found during the 5-year observation period . CONCLUSIONS The present study shows good 5-year results with small ISFPP in the m and ible , as well as in the maxilla . No significant differences were found in failure rate and marginal bone loss around implants with a machined rather than a TiO(2)-blasted surface . J Prosthodont 2001;10:2 - 7 BACKGROUND Comparatively few studies with at least 5 years of follow-up are available that describe the use of implants in prosthetic rehabilitation of partially edentulous patients . R and omized , controlled clinical studies that evaluated the effect of different surface design s of screw-shaped implants on the outcome of treatment are also sparse . OBJECTIVE To determine , in a prospect i ve r and omized , controlled clinical trial , the outcome of restorative therapy in periodontitis-susceptible patients who , following basic periodontal therapy , had been restored with implants with either a machined- or a rough-surface topography . MATERIAL AND METHODS Fifty-one subjects ( mean age , 59.5 years ) , 20 males and 31 females who , following treatment of moderate-to-advanced chronic periodontitis , required implant therapy for prosthetic rehabilitation were recruited . Seventeen of the patients were current smokers . Following the active treatment , all subjects were included in an individually design ed maintenance program . A total of 56 fixed partial dentures ( FPDs ) and a total of 149 screw-shaped , and self-tapping implants ( Astra Tech implants ) -- 83 in the maxilla and 66 in the m and ible -- were installed in a two-stage procedure . Each patient received a minimum of two implants and by r and omization every second implant that was installed had been design ed with a machined surface and the remaining with a roughened Tioblast surface . Abutment connection was performed 3 - 6 months after implant installation . Clinical and radiographical examinations were performed following FPD connection and once a year during a 5-year follow-up period . The analysis of peri-implant bone-level alterations was performed on subject , FPD and implant levels . RESULTS Four patients and four FPDs were lost to the 5 years of monitoring . One implant ( machined surface ) did not properly integrate ( early failure ) , and was removed at the time of abutment connection . Three implants were lost during function and a further eight implants could not be accounted for at the 5-year follow-up examination . The overall failure rate at 5 years was 5.9 % ( subject level ) , 5.3 % ( FPD level ) and 2.7 % ( implant level ) . Radiographic signs of loss of osseointegration were not found at any of the implants during the 5-year observation period . During the first year in function there was on average 0.33 ( SD , 0.61 ) mm loss of peri-implant marginal bone on the subject and FPD levels and 0.31 ( 0.81 ) mm on the implant level . During the subsequent 4 years , the peri-implant bone-level alterations were small . The calculated annual change in peri-implant bone level was -0.02 ( 0.15 ) on subject and FPD levels and -0.03 ( 0.20 ) on the implant level . Thus , the mean total bone-level change over the 5-year interval amounted to 0.41 mm on all three levels of analysis . In the interval between baseline and 5 years , the machined and the Tioblast implants lost on average 0.33 and 0.48 mm , respectively ( p>0.05 ) . CONCLUSION The present r and omized , controlled clinical trial that included partially edentulous periodontitis-susceptible subjects demonstrated that bone loss ( i ) during the first year of function as well as annually thereafter was small and ( ii ) did not vary between implants with machined- or rough-surface design BACKGROUND The immediate loading of implants with a porous anodized surface is a well-described technique . Few data are however available on the long-term outcomes . PURPOSE The aim of this prospect i ve study was to assess the 10-year performance of TiUnite implants supporting fixed prostheses placed with an immediate loading approach in both postextractive and healed sites . MATERIAL S AND METHODS All patients received a fixed provisional restoration supported by immediately loaded parallel design , self-tapping implants with a porous anodized TiUnite surface , and an external-hexagonal connection . Both healed and postextractive cases were included . Success and survival rate for restorations and implants , changes in marginal peri-implant bone level , probing depth measurements , biological or technical complications , and any other adverse event were recorded at yearly follow-up up to 10 years after surgery . RESULTS A total of 210 implants fulfilled the inclusion criteria and were consecutively placed in 59 patients . Forty-seven ( 22.38 % ) implants were lost because of the recalled patient refused to attend the planned 10-year follow-up . Five over 210 ( 2.38 % ) implants were lost . At the final follow-up , the accumulated mean marginal bone loss and probing depth were , respectively , 1.93 mm ( SD 0.40 ) and 2.54 mm ( SD 0.44 ) for the implants placed in healed sites ( n = 84 ) ; 1.98 mm ( SD 0.37 ) and 2.63 mm ( SD 0.39 ) for the implants placed in postextractive sites ( n = 74 ) . The restorations examined achieved a cumulative 65.26 % success rate and 97.96 % survival rate . The implants placed in healed and postextractive sites , respectively , achieved a 98.05 % and a 96.52 % cumulative survival rate . CONCLUSIONS Positive results in terms of bone maintenance in the long-term perspective are to be expected using immediately loaded implants with a TiUnite porous anodized surface in both postextractive and healed sites when adequate levels of oral hygiene are kept |
11,199 | 18,254,044 | H and washing can reduce diarrhoea episodes by about 30 % .
This significant reduction is comparable to the effect of providing clean water in low-income areas . | BACKGROUND Diarrhoea is a common cause of morbidity and a leading cause of death among children aged less than five years , particularly in low- and middle-income countries .
It is transmitted by ingesting contaminated food or drink , by direct person-to-person contact , or from contaminated h and s. H and washing is one of a range of hygiene promotion interventions that can interrupt the transmission of diarrhoea-causing pathogens .
OBJECTIVES To evaluate the effects of interventions to promote h and washing on diarrhoeal episodes in children and adults . | Elementary school-age children are particularly vulnerable to infections . While h and washing is the best method of preventing infections , many elementary schools are housed in buildings that have barriers to effective h and hygiene . The purpose of this study was to determine the effectiveness of an alcohol gel as an adjunct to h and washing in reducing absenteeism secondary to infectious illness . Two-hundred and fifty-three elementary school children were r and omized by classroom into an experimental or control group . With a crossover design , all children participated in both groups , with a one-week washout period between phases . A 45-minute “ Germ Unit ” was taught to all children as they started the experimental phase and a st and ard unit on h and hygiene was taught as they started the control phase . Sixty-nine children were absent due to illness while in the control group . Thirty-nine children became ill while in the experimental group . Alcohol gel as an adjunct to h and washing was shown to be effective in reducing absenteeism due to infectious illness by 43 % From October 1981 to September 1984 , the authors conducted a three-year longitudinal study of diarrhea among infants and toddlers attending day care centers in Maricopa County , Arizona . In the third year of study , they evaluated the effects on diarrhea rates of staff training without external monitoring and of active surveillance conducted throughout the study . From 21 study day care centers , they r and omly selected 10 ( " intervention day care centers " ) to receive staff training in procedures to reduce transmission of infectious diarrhea . Continuing active surveillance in the 10 intervention and 11 control day care centers found no difference between diarrhea rates in intervention day care centers in the pre- and posttraining years and no difference between diarrhea rates in the two groups of centers either before or after the training intervention . Biweekly family-based surveys during the two months after training also demonstrated no difference between infant-toddler diarrhea rates in intervention and control day care centers . These surveys found the 21 study day care centers to have significantly higher diarrhea rates than did day care homes or households not using day care , but significantly lower rates than day care centers not included in the active surveillance . Continuous surveillance without training was associated with a significant decrease in diarrheal illness during the course of longitudinal study . One-time staff training without subsequent monitoring did not result in additional decreases and did not lower day care center diarrhea rates to the levels observed in day care homes and households not using day care The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers . A r and omized field trial was conducted in 52 day care centers in Quebec , Canada , between September 1 , 1996 and November 30 , 1997 . Absences for any reasons and the daily occurrence of colds and /or diarrhea in toddlers were recorded on calendars by the educators . The number of fecal coliforms on children 's h and s and on educators ' h and s was measured during three unannounced visits . Overall , 1,729 children were followed in 47 day care centers for a total of 153,643 child-days . The incidence rate of diarrhea was considerably reduced by the effect of monitoring ( IRR = 0.73 , 95 % CI = 0.54,0.97 ) , and the intervention reduced the incidence rate of upper respiratory tract infections ( IRR = 0.80 , 95 % CI = 0.68,0.93 ) . Monitoring alone also had an important effect in reducing the level of bacterial contamination on children 's and educators ' h and s. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers Diarrhea has been recognized as a frequent health problem among children enrolled in day-care centers . Thus , we evaluated the effect of a h and washing program in two day-care centers ( HWC ) on the incidence of diarrhea among children when compared to children in two control centers ( CC ) . After the program was begun , the incidence of diarrhea at the HWC began to fall and after the second month of the study was consistently lower than that at the CC . The incidence of diarrhea in the HWC was approximately half that of the CC for the entire 35-week study period . Adenoviruses , rotavirus , Giardia lamblia , and enteropathogenic Escherichia coli were found in the stools of a small number of ill children , but not pathogen was identified in the stools of most children with diarrhea . These results suggest that a h and washing program will probably prevent at least some of the diarrhea in day-care centers Transmission of enteric pathogens is facilitated in child day care centers , including family day care homes , by frequent and intimate exposure among susceptible hosts , with diaper changing as the highest-risk procedure for such transmission . The objective of this study was to evaluate the effectiveness of an intervention program in decreasing the incidence of infectious disease symptoms in children attending family day care homes during a 12-month period . Each of 24 family day care homes was r and omly assigned to an intervention or control group . The intervention included four components : ( 1 ) a h and washing educational program and ( 2 ) use of vinyl gloves , ( 3 ) use of disposable diaper changing pads , and ( 4 ) use of an alcohol-based h and rinse by the day care provider . Symptoms of enteric disease ( diarrhea and vomiting ) were significantly reduced in intervention family day care homes ( p less than or equal to 0.05 ) , whereas respiratory symptoms were not significantly different between intervention and control family day care homes ( p = 0.35 ) . Diarrhea was reported in 1 of every 100 child care days , representing one diarrhea episode per month in a typical family day care home OBJECTIVES To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting h and washing with soap . METHODS The study was conducted in squatter settlements of Karachi , Pakistan , where diarrhoea is a leading cause of childhood death . Interventions were r and omly assigned to 47 neighbourhoods . Households in 10 neighbourhoods received diluted bleach and a water vessel ; nine neighbourhoods received soap and were encouraged to wash h and s ; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel ; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash h and s ; and nine neighbourhoods were followed as controls . Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea . RESULTS Study participants in control neighbourhoods had diarrhoea on 5.2 % of days . Compared to controls , participants living in intervention neighbourhoods had a lower prevalence of diarrhoea : 55 % ( 95 % CI 17 % , 80 % ) lower in bleach and water vessel neighbourhoods , 51 % ( 95 % CI 12 % , 76 % ) lower in h and washing promotion with soap neighbourhoods , 64 % lower ( 95 % CI 29 % , 90 % ) in disinfectant-disinfectant neighbourhoods , and 55 % ( 95 % CI 18 % , 80 % ) lower in disinfectant-disinfectant plus h and washing with soap neighbourhoods . CONCLUSIONS With an intense community-based intervention and supplies provided free of cost , each of the home-based interventions significantly reduced diarrhoea . There was no benefit by combining h and washing promotion with water treatment Intensive h and washing promotion can reduce diarrheal and respiratory disease incidence . To determine whether less intensive , more scalable interventions can improve health , we evaluated a school-based h and washing program . We r and omized 87 Chinese schools to usual practice s : st and ard intervention ( h and washing program ) or exp and ed intervention ( h and washing program , soap for school sinks , and peer hygiene monitors ) . We compared student absence rates , adjusting for cluster design . In control schools , children experienced a median 2.0 episodes ( median 2.6 days ) of absence per 100 student-weeks . In st and ard intervention schools , there were a median 1.2 episodes ( P = 0.08 ) and 1.9 days ( P = 0.14 ) of absence per 100 student-weeks . Children in exp and ed intervention schools experienced a median 1.2 episodes ( P = 0.03 ) and 1.2 days ( P = 0.03 ) of absence per 100 student-weeks . Provision of a large-scale h and washing promotion program and soap was associated with significantly reduced absenteeism . Similar programs could improve the health of children worldwide BACKGROUND Diarrhoeal disease is a leading cause of morbidity in young children in rural Zaire . Few diarrhoea prevention programmes have been implemented in B and undu Province , where available data suggest an annual prevalence rate of 10 % . The urgent need to reduce diarrhoeal morbidity in Zaire , together with the potential effectiveness and feasibility of hygiene education as a diarrhoea prevention strategy , led to the development of the present research project . METHODS A r and omized , controlled trial of an education intervention to reduce diarrhoea through improved personal and domestic hygiene behaviours was conducted in 18 geographically separate village clusters ( sites ) in rural Zaire . For 12 weeks baseline information on the diarrhoeal morbidity of 2082 children aged 3 - 35 months was collected at weekly home visits , and structured observations of hygiene practice s related to diarrhoea were made on a subset of 300 families . Intervention messages addressed disposal of animal faeces from the yard , h and washing after defecation and before meal preparation and eating , and disposal of children 's faeces . Three months after the start of the intervention and exactly 1 year after the baseline studies , a second diarrhoeal morbidity study and a second observational study were conducted in order to evaluate the intervention . RESULTS Children in intervention communities experienced an 11 % reduction in the risk of reporting diarrhoea during the peak diarrhoeal season , compared to controls ( P < 0.025 ) . The largest differences were seen among children aged 24 - 35 months , with those from intervention communities reporting significantly fewer episodes , shorter mean duration s and hence fewer days of diarrhoea . There was some evidence that greater reductions in diarrhoea occurred in sites where the quality of the intervention , a scored measure of volunteer efficacy and community participation , was highest . CONCLUSIONS The results of this study suggest that hygiene education may be an effective approach to reduce the incidence and duration of diarrhoeal episodes in rural Zaire . Children aged 2 years appear to benefit the most . A Hawthorne effect of the education may contribute to diarrhoeal reductions A case-control study was performed to develop an empirically based intervention for improving water-sanitation practice s and rates of childhood diarrhea among families residing in urban Bangladesh . For three months fortnightly , histories of diarrhea were taken for all children under six years of age among 1,350 families to estimate age-specific rates of diarrhea in the population . A total of 247 r and omly sample d families , termed sentinel families , were visited once during the study for prolonged observations of water-sanitation practice s. Behaviors potentially affecting incidence of diarrhea were compared in a case group ( n = 45 ) , defined as sentinel families whose children had rates at least 1.7 times the rates expected for similarly aged children , and in a control group ( n = 53 ) , defined as sentinel families without any episodes of childhood diarrhea during the period of observation . Three practice s differentiated the two groups : more control ( 82 % ) than case ( 53 % ) mothers who were observed to prepare food washed their h and s before beginning the preparation ( p less than 0.01 ) ; fewer control families ( 33 % ) than case families ( 80 % ) had ambulatory children who , when observed to defecate , did so in the family 's living area ( p less than 0.01 ) ; and fewer control ( 30 % ) than case ( 47 % ) families had children who were observed to place garbage or waste products in their mouth ( p less than 0.10 ) . Focus on these three empiric associations enabled the design of a community-specific educational intervention which is simple in construction and based upon naturally occurring , financially feasible , salutory practice Context Household cleaning products containing antibacterial ingredients are widely available and popular . Although manufacturers use cl aims of health benefits to market these products , evidence linking the use of antibacterial products to health outcomes has been lacking . Contribution This innovative trial found no difference in episodes of infectious disease symptoms over one year in 228 inner-city households r and omly assigned to use antibacterial household cleaning products or identically packaged products without antibacterial ingredients . Implication s These findings highlight the need to better educate consumers about the use and limitations of household antibacterial cleaning products . The Editors Changing demographic and social patterns , such as more working parents , increased numbers of meals eaten in restaurants , and more child-care outside of the home , are causing concomitant changes in patterns of infectious diseases ( 1 ) . For example , recent foodborne outbreaks have result ed from widespread distribution of contaminated foods , such as meat or ice cream . Media attention to such outbreaks and the result ant public concern about disease transmission may be one reason for the burgeoning of various products that are labeled antibacterial and that are readily available for personal hygiene and general cleaning . These demographic and social shifts raise the question of the relative importance of home hygienic practice s in the prevention of infectious diseases . The home environment has been implicated as one important source of spread of infectious diseases ( 2 - 4 ) , and hygienic interventions have result ed in reduced incidence , particularly in less-developed countries ( 5 ) . In the United States , several studies have demonstrated the effectiveness of hygienic interventions in reducing transmission of infections in child-care centers and schools ( 6 - 9 ) . However , despite the fact that 75 % of liquid and 29 % of bar soaps available in the U.S. consumer market contain antibacterial ingredients ( 10 ) , their benefits in terms of reducing the incidence of infectious diseases in households have not been demonstrated . In addition , concerns have been raised about the potential for long-term use of such products to increase resistance to antiseptics or cross-resistance with antibiotics ( 11 , 12 ) . Therefore , we sought to evaluate the effect of antibacterial cleaning and h and washing products on the occurrence of infectious disease symptoms in households . Methods In this double-blind clinical trial , we r and omly assigned households to one of 2 intervention groups : those who used h and washing and household cleaning products with antibacterial ingredients and those who used products without such ingredients . The interventions lasted for 48 weeks . Sample and Setting We conducted the study in an inner-city neighborhood in northern Manhattan , New York , with a predominantly immigrant population in multigenerational households . Almost 30 % of residents spoke little or no English , and about 90 % of the households had telephones ( 13 ) . To qualify for the study , a household unit had to include 3 or more persons with at least one preschool-age child and had to have access to a telephone . In addition , household members had to speak English or Spanish . In a preliminary survey ( 14 ) conducted in this neighborhood , 78.5 % of 398 households reported infectious disease symptoms within the previous month , and in 37.9 % of these households , at least one person sought medical attention and received specific treatment or antibiotics for an infectious disease symptom or symptoms . On the basis of this pilot work , we concluded that a r and omized clinical trial with sufficient statistical power was feasible . Recruitment was by word of mouth , referral , and English- and Spanish- language flyers ( preapproved by the institutional review board ) posted throughout the community . Participants were recruited by an experienced , trained interviewer who resided in the community and who was a native Spanish speaker . We determined sample size by power analysis . With 100 households for each intervention group and a household incidence of infectious disease symptoms of about 35 % per month , on the basis of the pilot study , it would be possible to detect an absolute difference between the 2 intervention groups of 20 percentage points or more ( for example , from 35 % to 15 % ) with a power of 80 % and an value of less than 0.05 ( 15 ) . We recruited an additional 19 % above this desired sample size to account for potential loss to follow-up and dropouts . A total of 238 households were r and omly assigned , and 224 ( 94.1 % ) completed the entire 48 weeks of data collection . Fourteen households ( 5.9 % ) did not complete the entire study period , 9 ( 64.3 % ) because the household moved out of the study area , 3 ( 21.4 % ) because the household did not continue to use the products , and 2 ( 14.3 % ) because the household was inadvertently supplied with the wrong product ( Figure 1 ) . Figure 1 . Profile of r and omized , clinical trial . Intervention Criteria for selecting products to be tested were as follows : The products had to be readily available over the counter ; have the same or similar formulation , except for the presence or absence of an antibacterial ingredient ; be representative of a particular category of product so that results could be generalized to other similar products ; and be developed by reputable companies known for good manufacturing practice s. Antibacterial was defined as the presence of triclosan , quaternary ammonium compounds , hypochlorite , or another recognized microbicidal agent in amounts greater than preservative levels . Also , the product label had to include the term antibacterial or disinfectant . Households r and omly assigned to the antibacterial group were provided with the following : a liquid kitchen spray and all- purpose hard-surface cleaner containing a quaternary ammonium compound , liquid h and washing soap containing triclosan , and a laundry detergent containing oxygenated bleach . The nonantibacterial group received parallel products with similar compositions that did not contain antibacterial ingredients . Both intervention groups were provided with the same liquid dishwashing detergent and bar soap , neither of which contained antibacterial ingredients . Procedures The study was approved by the Columbia Presbyterian Medical Center Institutional Review Board . After we obtained written informed consent , households were r and omly assigned to one of the intervention groups ; the master key code was retained by the biostatistician . All products were provided without cost , were packaged identically with a generic label indicating their use , and were delivered to the household monthly . On the initial home visit , we collected baseline data on home hygiene practice s and the presence of infectious disease symptoms within the previous month for each household member by using our Home Hygiene Assessment Form . We made a weekly telephone call and a monthly home visit to each household . During the monthly visit , we assessed adherence to the product regimens by weighing the remainder of products with a postal scale and inspecting the home for the presence of other products . Every 3 months , we assessed symptoms in individual household members , and the Home Hygiene Assessment Form was readministered to determine whether any hygienic practice s had changed . We conducted an average of 226 interviews each week . For most of the households ( 98.8 % ) , at least 20 weekly interviews were completed , and for 89.0 % of households , 45 or more weekly interviews were completed . Data were collected by 3 interviewers who received extensive training using a written orientation manual , practice sessions with return demonstrations , and inter-rater reliability assessment s. The interviewers and project director were native Spanish speakers ; 3 were physicians , and the fourth was a trained community health worker . Initially and on a r and om monthly basis , each interviewer was accompanied by the project director on 10 % of the home visits for ongoing quality control . Instrument Because cleaning and hygiene practice s within the home would probably affect the dependent variable , infectious disease symptoms , we collected extensive data on cleaning and hygiene practice s at baseline and at quarterly intervals . The Home Hygiene Assessment Form is a 31-page interview booklet that includes questions about demographic characteristics and illness ( age , sex , ethnicity , country of birth , hours per week spent outside the home , type of work for adults , school or child-care arrangements for children , state of health , and presence of chronic diseases ) , home hygiene practice s ( 54 items ) , and other relevant household factors ( numbers and ages of household members , size of living space , presence of pets and visitors , type of building , and heating and cooling systems ) . We also asked participants about their attitudes and beliefs about how germs are spread and what they did to prevent infections in their home . The components of the instrument were originally derived from a literature search , focus groups of consumers , and a panel of environmental sanitation experts . The Home Hygiene Assessment Form was tested extensively for validity and reliability ( 16 ) . Whenever possible , direct observations were made to confirm self-reports . Measurement of Dependent Variable ( Infectious Disease Symptoms ) The presence of infections was assessed symptomatically . We instructed participants to call their interviewer if any member of the household had vomiting , diarrhea , fever , sore throat , cough , runny nose , skin infection , or conjunctivitis ( pinkeye ) . We provided each household with a supply of single-use thermometers ( Tempa-DOT , 3 M Health Care , St. Paul , Minnesota ) and gave instructions for their use . In the weekly telephone call from the interviewer , we also solicited information on symptoms . If participants reported a cough , they were queried by a physician about whether BACKGROUND More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year . We undertook a r and omised controlled trial to assess the effect of h and washing promotion with soap on the incidence of acute respiratory infection , impetigo , and diarrhoea . METHODS In adjoining squatter settlements in Karachi , Pakistan , we r and omly assigned 25 neighbourhoods to h and washing promotion ; 11 neighbourhoods ( 306 households ) were r and omised as controls . In neighbourhoods with h and washing promotion , 300 households each were assigned to antibacterial soap containing 1.2 % triclocarban and to plain soap . Fieldworkers visited households weekly for 1 year to encourage h and washing by residents in soap households and to record symptoms in all households . Primary study outcomes were diarrhoea , impetigo , and acute respiratory-tract infections ( ie , the number of new episodes of illness per person-weeks at risk ) . Pneumonia was defined according to the WHO clinical case definition . Analysis was by intention to treat . FINDINGS Children younger than 5 years in households that received plain soap and h and washing promotion had a 50 % lower incidence of pneumonia than controls ( 95 % CI ( -65 % to -34 % ) . Also compared with controls , children younger than 15 years in households with plain soap had a 53 % lower incidence of diarrhoea ( -65 % to -41 % ) and a 34 % lower incidence of impetigo ( -52 % to -16 % ) . Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap . INTERPRETATION H and washing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely , diarrhoea and acute lower respiratory infections . H and washing with daily bathing also prevents impetigo Little is known about effects of public use of antimicrobial h and washing soap . A double-blinded , r and omized clinical trial of h and s of primary caretakers in 238 inner city households was conducted in which effects of plain or antimicrobial ( containing 0.2 % triclosan ) h and washing soap on bacterial counts of the h and s were compared before and after a single wash and before and after h and washing following a year of product use . The r and omly assigned product was provided without cost to each household during monthly home visits , and compliance with product use was monitored . Households were contacted by telephone weekly and with a home visit monthly for 11 months . H and cultures were obtained before and after h and washing at baseline and after 11 months , using a modified glove juice technique . Overall , there were no significant differences in pre-to-post h and washing counts at baseline ( p = 0.41 ) , but by the end of one year , post-wash counts were significantly lower than pre-wash ( p = 0.000 ) for those using either antimicrobial or plain soap . There were no significant differences in mean log counts either before or after h and washing between those using the antimicrobial or plain soap at baseline or after a year of use ( all p values > 0.28 ) . For the group using antimicrobial soap , higher counts were observed post-h and washing in 31.3 % of paired sample s at baseline and 26.7 % after one year ( p = 0.03 ) . A single h and wash had minimal effect on quantity of h and flora , but there were significant effects over time , regardless of whether antimicrobial or plain soap was used . In the absence of more definitive evidence , the risk-benefit ratio argues in favor of targeted rather than ubiquitous , general household use of antimicrobial soap CONTEXT Washing h and s with soap prevents diarrhea , but children at the highest risk of death from diarrhea are younger than 1 year , too young to wash their own h and s. Previous studies lacked sufficient power to assess the impact of household h and washing on diarrhea in infants . OBJECTIVE To evaluate the effect of promoting household h and washing with soap among children at the highest risk of death from diarrhea . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi , Pakistan . Field workers visited participating households at least weekly from April 15 , 2002 , to April 5 , 2003 . Eligible households located in the study area had at least 2 children younger than 15 years , at least 1 of whom was younger than 5 years . INTERVENTIONS Weekly visits in 25 neighborhoods to promote h and washing with soap after defecation and before preparing food , eating , and feeding a child . Within intervention neighborhoods , 300 households ( 1523 children ) received a regular supply of antibacterial soap and 300 households ( 1640 children ) received plain soap . Eleven neighborhoods ( 306 households and 1528 children ) comprised the control group . MAIN OUTCOME MEASURE Incidence density of diarrhea among children , defined as the number of diarrheal episodes per 100 person-weeks of observation . RESULTS Children younger than 15 years living in households that received h and washing promotion and plain soap had a 53 % lower incidence of diarrhea ( 95 % confidence interval [ CI ] , -65 % to -41 % ) compared with children living in control neighborhoods . Infants living in households that received h and washing promotion and plain soap had 39 % fewer days with diarrhea ( 95 % CI , -61 % to -16 % ) vs infants living in control neighborhoods . Severely malnourished children ( weight for age z score , < -3.0 ) younger than 5 years living in households that received h and washing promotion and plain soap had 42 % fewer days with diarrhea ( 95 % CI , -69 % to -16 % ) vs severely malnourished children in the control group . Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap . CONCLUSION In a setting in which diarrhea is a leading cause of child death , improvement in h and washing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea Patients with AIDS frequently develop diarrhoeal illness . In this r and omized , controlled study , 260 patients were screened for those who had not had diarrhoea in the preceding 3 months and who had received a stable highly active antiretroviral therapy regimen for at least 6 weeks prior to the study enrollment . A total of 148 patients met the inclusion criteria and were enrolled : 75 patients were r and omly assigned to an intensive h and washing intervention ( i.e. h and washing after defecation , after cleaning infants who had defecated , before preparing food , before eating , and before and after sex ) and 73 patients were r and omly assigned to the control group . Patients in both groups were called weekly by telephone to determine compliance with h and washing and to determine the number of diarrhoeal episodes for the preceding week . Patients were observed for 1 year . Patients assigned to the intensive h and washing intervention group washed their h and s more frequently compared with the control group ( seven vs four times a day , respectively ; P < 0.05 ) and developed fewer episodes of diarrhoeal illness ( 1.24+/-0.9 vs 2.92+/-0.6 new episodes of diarrhoea , respectively ; P < 0.001 ) during the 1 year observation . The most common pathogens identified in both groups in patients who developed diarrhoeal illness were Giardia lamblia , Cryptosporidium , Entamoeba histolytica and Shigella flexneri . These data suggest that intensive h and washing reduces diarrhoeal illness in patients with AIDS UNLABELLED BACKGROUND AND HYPOTHESES : A substantial percentage of school absenteeism among children is related to transmissible infection . Rates of transmission can be reduced by h and washing with soap and water , but such washing occurs infrequently . This study tested whether an alcohol-free instant h and sanitizer ( CleanH and s ) could reduce illness absenteeism in school-age children . METHODS A 10-week , open-label , crossover study was performed on 420 elementary school-age children ( ages 5 - 12 ) . Students were given a brief orientation immediately prior to the start of the study on the relationship of germs , illness , and h and washing . Each student in the treatment group then received the test product in individual bottles , with instructions to apply one to two sprays to the h and s after coming into the classroom , before eating , and after using the restroom , in addition to their normal h and washing with soap and water . The control group was instructed to continue h and washing as normal with non-medicated soap . After 4 weeks of treatment and a 2-week wash-out period , the control and experimental groups were reversed . Data gathered on absenteeism were classified as gastrointestinal or respiratory related and normalized for nonillness-related absenteeism and school holidays . RESULTS Compared to the h and washing-only control group , students using CleanH and s were found to have 41.9 % fewer illness-related absence days , representing a 28.9 % and a 49.7 % drop in gastrointestinal- and respiratory-related illnesses , respectively . Likewise , absence incidence decreased by 31.7 % , consisting of a 44.2 % and 50.2 % decrease in incidence of gastrointestinal- and respiratory-related illnesses , respectively . No adverse events were reported during the study . CONCLUSIONS Daily use of the instant h and sanitizer was associated with significantly lower rates of illness-related absenteeism BACKGROUND AND OBJECTIVES H and washing prevents communicable illness . We evaluated the effect of a m and atory , scheduled h and -washing program in elementary school children on absenteeism due to acute communicable illness . METHODS The study was conducted at Trombley Elementary School in Grosse Pointe Park , Mich. The intervention group , approximately half of the school children ( n = 143 , including all grade s 1 - 5 ) , washed their h and s a minimum of four scheduled times a day . The control group ( n = 162 ) continued h and -washing practice s as usual . RESULTS Of the 37 school days examined , children in the h and -washing group were absent fewer days than the control group due to all acute communicable illness ( relative risk = .75 ) . There were less days of absence due to gastrointestinal symptoms ( relative risk = .43 ) . The difference in absence due to respiratory symptoms was not statistically significant . CONCLUSIONS A scheduled h and -washing program will reduce acute communicable ( gastrointestinal ) illnesses in elementary school-age children Diarrheal diseases pose a major threat to the health of people living in developing countries , particularly where there is poverty and a poor environment . The effect of h and washing in reducing the incidence of diarrhea in day-care centers has been reported recently . The present study is a prospect i ve community based study conducted to evaluate the effect of h and washing on the incidence of diarrheal disease in Calcutta slums . H and washing was implemented in 1 slum and the other nearby slum , without h and washing program , served as control . The incidence of watery diarrhea during the 13 month period , between the study and control groups was not significantly different . However , the incidence of dysentery in individuals above 5 years of age in the control group was significantly higher as compared to those in the study group ( p 0.05 ) . The results of this study indicate that h and washing with soap may reduce the incidence of dysenteric cases in the community by interruption of transmission of the pathogens from 1 person to the other This study examines the effect of maternal personal and domestic hygiene on the incidence of diarrhoea in children aged 6 - 23 months from rural areas around Teknaf , Bangladesh . The intervention area received augmented water supply through h and pumps and health education while the control area received no project inputs . From July 1980 to June 1983 , diarrhoea incidence was recorded weekly while mothers ' personal and domestic hygiene was observed yearly . Annual incidence of diarrhoea in 314 children from the intervention area and 309 children from the control area was analysed in relation to maternal personal and domestic hygiene , controlling for education and occupation of household head and household size . Results show that , in both areas , use of h and pump water for drinking and washing , removal of child 's faeces from the yard , and maternal h and washing before h and ling food and after defaecation of self and child , observed together , decreased yearly diarrhoea incidence in children by more than 40 % compared to children living in households where none or only one of these practice s was observed An educational intervention was design ed to improve three water-sanitation behaviors empirically shown to be associated with high rates of childhood diarrhea in Dhaka , Bangladesh : lack of h and washing before preparing food , open defecation by children in the family compound , and inattention to proper disposal of garbage and feces , increasing the opportunity for young children to place waste products in their mouth . Fifty-one communities , each comprising 38 families , were r and omized either to receive ( n = 25 ) or not to receive ( n = 26 ) the intervention . During the six months after the intervention , the rate of diarrhea ( per 100 person-weeks ) in children under six years of age was 4.3 in the intervention communities and 5.8 in the control communities ( 26 % protective efficacy ; p less than 0.0001 ) . A corresponding improvement in h and washing practice s before preparing food was noted , although no improvement was observed for defecation and waste disposal practice s. These data suggest that educational interventions for water-sanitation practice s can have an important beneficial effect upon childhood diarrhea in developing countries , particularly when the interventions are design ed in a simple way to promote naturally occurring salutory behaviors that are empirically associated with lower rates of childhood diarrhea A community-based intervention was developed through direct participation of the target population in assessment and iterative trials to improve hygiene practice s and to reduce childhood diarrhoea in lowl and rural Bangladesh . A total of 185 ( 98 % ) households with children ages 0 - 18 months in five contiguous villages were targeted for the interventions . A comparison site was selected for a detailed observational study and for use as a control for the intervention . About 97 % of all households with children ages 0 - 18 months were enrolled for study at the control site . Children in this age group were targeted because at this developmental stage they were most vulnerable to diarrhoeal morbidity and malnutrition ( related to unhygienic practice s ) . The intervention was implemented with the assistance of village leaders through a " Clean Life " campaign by local project workers and volunteer mothers who were chosen from the target households . The intervention activities started in January 1986 and lasted for 7 months . Higher adoption rates of the intervention were associated with better cleanliness status , which was related to lower diarrhoea and malnutrition rates in the intervention site . The results of between-site longitudinal analyses showed that after the intervention , the intervention site had substantially higher cleanliness scores , lower diarrhoeal morbidity , and better growth status compared to those of the control site , with differences increasing over time . The findings suggest that this type of community-based intervention can be very beneficial in modifying hygiene behaviours and lowering childhood diarrhoea and malnutrition Background . Diarrheal infections are common in children who attend child care , and preventing transmission of disease in this setting depends on actions by child care staff . We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures . Methods . We performed a cluster r and omized , controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia . The intervention was training of child care staff about transmission of infection and h and washing and focused on both staff and child behavior . Implementation of the intervention was recorded by an observer . Illness was measured by parent report in telephone interviews every 2 weeks . Results . There were 311 child-years of surveillance for diarrheal episodes . The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers . Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50 % . However , the impact of the intervention was confined to children over 24 months of age . For those centers in which children 's compliance with h and washing was high , diarrheal episodes were reduced by 66 % . Conclusions . This trial supports education about infection control , for staff and children in child care , as a means of reducing transmission of diarrhea . Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age BACKGROUND Several studies have indicated a connection between h and washing and illness-related absenteeism in school setting s. The difficulty of ensuring consistent and effective h and washing among student population s has also been noted . The purpose of this study was to assess the effectiveness of the use of an alcohol gel h and sanitizer in the classroom to help decrease the illness-related absentee rate for elementary school students . METHODS This study involved 5 individual school districts , 16 individual schools , and more than 6000 students in Delaware , Ohio , Tennessee , and California . Individual schools in each district were paired into product and control groups . In the product group schools , an alcohol gel h and sanitizer was used by the students and staff when entering and leaving the classroom . Absenteeism due to infection was recorded , and the data were statistically analyzed . RESULTS The overall reduction in absenteeism due to infection in the schools included in this study was 19.8 % for schools that used an alcohol gel h and sanitizer compared with the control schools ( P < .05 ) . Data from the school system with the largest teacher population ( n = 246 ) showed that teacher absenteeism decreased 10.1 % ( trend ) in the schools where sanitizer was used . CONCLUSION Elementary school absenteeism due to infection is significantly reduced when an alcohol gel h and sanitizer is used in the classroom as part of a h and hygiene program |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.